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
⌀ |
|---|---|---|---|---|
11,200 | 25,194,208 | We found evidence for both common and distinct patterns of neural activation .
Limbic engagement was common to SAD and WS during facial emotion processing , although we observed opposite patterns of activation for each disorder .
Compared to HC , SAD cases showed hyperactivation of the amygdala , the parahippocampal gyrus and the globus pallidus .
Compared to controls , participants with WS showed hypoactivation of these regions .
Differential activation in a number of regions specific to either condition was also identified : SAD cases exhibited greater activation of the insula , putamen , the superior temporal gyrus , medial frontal regions and the cuneus , while WS subjects showed decreased activation in the inferior region of the parietal lobule .
The identification of limbic structures as a shared correlate and the patterns of activation observed for each condition may reflect the aberrant patterns of facial emotion processing that the two conditions share , and may contribute to explaining part of the underlying neural substrate of exaggerated/diminished fear responses to social cues that characterize SAD and WS respectively .
We believe that insights from WS and the inclusion of this syndrome as a control group in future experimental studies may improve our underst and ing of the neural correlates of social fear in general , and of SAD in particular | BACKGROUND Social Anxiety Disorder ( SAD ) and Williams-Beuren Syndrome ( WS ) are two conditions which seem to be at opposite ends in the continuum of social fear but show compromised abilities in some overlapping areas , including some social interactions , gaze contact and processing of facial emotional cues .
The increase in the number of neuroimaging studies has greatly exp and ed our knowledge of the neural bases of facial emotion processing in both conditions .
However , to date , SAD and WS have not been compared . | The amygdala is known to play an important role in conscious and unconscious processing of emotional and highly arousing stimuli . Neuroanatomical evidence suggests that the amygdala participates in the control of autonomic responses , such as skin conductance responses ( SCRs ) , elicited by emotionally salient stimuli , but little is known regarding its functional role in such control . We investigated this issue by showing emotional visual stimuli of varying arousal to patients with left ( n = 12 ) , right ( n = 8) , and bilateral ( n = 3 ) amygdala damage and compared their results with those from 38 normal controls . Stimuli were presented both subliminally ( using backward masking ) and supraliminally under lateralized presentation to one visual hemifield . We collected SCRs as a physiological index of emotional responses . Subjects subsequently rated each stimulus on valence and arousal under free viewing conditions . There were two key findings : ( 1 ) impaired overall SCR after right amygdala damage ; and ( 2 ) impaired correlation of SCR with the rated arousal of the stimuli after left amygdala damage . The second finding was strengthened further by finding a positive correlation between the evoked SCR magnitude and postsurgery amygdala volume , indicating impaired autonomic responses with larger tissue damage . Bilateral amygdala damage result ed in severe impairments on both of the above measures . Our results provide support for the hypothesis that the left and right amygdalae subserve different functions in emotion processing : the left may decode the arousal signaled by the specific stimulus , whereas the right may provide a global level of autonomic activation triggered automatically by any arousing stimulus Individuals with Williams syndrome ( WS ) are well known for their friendly behaviour and tendency to approach strangers indiscriminately as if everybody were their friend . This tendency to approach strangers is mirrored in their ratings of unfamiliar face stimuli . Here we examined their perception of unfamiliar expressive faces and found that individuals with WS do not always see faces as being highly approachable . Happy faces were rated as more approachable by individuals with WS than by controls . In contrast , the other less approachable face stimuli were rated lower on approachability by individuals with WS than by controls . Thus , it appears that although individuals with WS will discriminate people in terms of approachability , they have difficulty inhibiting their strong compulsion towards social interaction . The form of this strong pro-social compulsion is discussed both in terms of friendliness and in terms of the heightened salience of social stimuli ( social stimulus attraction ) In this study we investigated whether event-related near-infrared spectroscopy ( NIRS ) is suitable to measure changes in brain activation of the occipital cortex modulated by the emotional content of the visual stimuli . As we found in a previous pilot study that only positive but not negative stimuli differ from neutral stimuli ( with respect to oxygenated haemoglobin ) , we now measured the event-related EEG potentials and NIRS simultaneously during the same session . Thereby , we could evaluate whether the subjects ( n = 16 ) processed the positive as well as the negative emotional stimuli in a similar way . During the task , the subjects passively viewed positive , negative , and neutral emotional pictures ( 40 presentations were shown in each category , and pictures were taken from the International Affective Picture System , IAPS ) . The stimuli were presented for 3 s in a r and omized order ( with a mean of 3 s interstimulus interval ) . During the task , we measured the event-related EEG potentials over the electrode positions O1 , Oz , O2 , and Pz and the changes of oxygenated and deoxygenated haemoglobin by multichannel NIRS over the occipital cortex . The EEG results clearly show an increased early posterior negativity over the occipital cortex for both positive as well as negative stimuli compared to neutral . The results for the NIRS measurement were less clear . Although positive as well as negative stimuli lead to significantly higher decrease in deoxygenated haemoglobin than neutral stimuli , this was not found for the oxygenated haemoglobin Neuroimaging studies using angry or contemptuous human facial photographic stimuli have suggested amygdala hyper-responsivity in social anxiety disorder ( SAD ) . We sought to determine if an angry " schematic face " ( simple line drawing ) would evoke exaggerated amygdalar responses in SAD patients compared with healthy control ( HC ) subjects . Angry , happy , and neutral schematic faces were overtly presented to matched cohorts of 11 SAD and 11 HC subjects for passive viewing , whereas brain functional magnetic resonance imaging signal was measured at 1.5 Tesla . Voxel-wise analyses were performed using a r and om effects model in SPM99 . Compared with HC subjects , SAD patients exhibited exaggerated responses in the right amygdala for the Angry versus Neutral contrast . The findings of exaggerated amygdala responses to angry schematic faces in SAD converge with results from earlier neuroimaging studies and illustrate the potential utility of schematic faces for probing amygdala function in psychiatric disorders . One prospect i ve advantage of schematic faces is that they may minimize confounds related to gender , age , or race effects . However , extending earlier findings in healthy subjects , schematic faces appear more effective for probing amygdala responses to arousal-based ( Angry versus Neutral ) as opposed to valence-based ( Angry versus Happy ) contrasts Williams syndrome ( WMS ) , a rare disorder with a distinctive profile of medical , psychological , neurophysiological and neuroanatomical characteristics , results from hemizygous deletion of about 20 genes . The phenotype exhibits specific dissociations in higher cognitive functions : general cognitive deficits but spared linguistic abilities ; extreme spatial cognitive deficits , but intact face processing . Of special interest is an unusual social phenotype in WMS : an overly friendly , engaging personality and excessive sociability with strangers . In this first experimental study of social behavior in WMS , we report that WMS subjects show an abnormal positive bias in their social judgments of unfamiliar individuals , consistent with their behavior in real life . Our findings contribute to an underst and ing of the neural and genetic bases of human social behavior |
11,201 | 29,415,653 | Accordingly , lower doses ( ≤ 300 mg/day ) of allopurinol reduced the risk of TCE , unlike higher doses .
Conclusions Purine-like XOI may reduce the incidence of adverse CV outcomes .
However , higher doses of allopurinol ( > 300 mg/day ) may be associated with loss of CV protection | Background Xanthine oxidase inhibitors ( XOI ) , classified as purine-like ( allopurinol and oxypurinol ) and non-purine ( febuxostat and topiroxostat ) XOI , present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism .
Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury , and may be implicated in the pathogenesis of heart failure , hypertension , and ischemic heart disease .
However , there is contradictory evidence regarding the possible cardiovascular ( CV ) protective effect exerted by XOI .
Our objective is to compare the incidence of major adverse cardiovascular events ( MACE ) , mortality , total ( TCE ) and specific CV events in r and omized controlled trials ( RCTs ) testing XOI against placebo or no treatment . | Objectives : To assess the clinical relevance ( functional outcome ) of a 3-month allopurinol regimen in patients with high serum uric acid ( SUA ) levels and acute ischemic stroke without considering the changes in SUA levels . Material s and Methods : In a r and omized , double-blind , controlled study , 70 patients ( 45 females , 25 males ) with acute ischemic stroke who had elevated levels of SUA were included . They were divided in two 35-patient groups to investigate the effect of 3 months of an allopurinol ( 200 mg/day ) regimen versus placebo on their functional outcome , which was evaluated using a modified Rankin scale . Results : The overall mean age was 68.9 ± 11.33 years ( range 27 - 89 ) . The final favorable functional status ( mRS = 0 - 2 ) was 23 ( 65.7 % ) and 14 ( 40.0 % ) in the treated and placebo groups , respectively , which was strongly associated with allopurinol consumption ( OR = 4.646 , p = 0.014 ) and age ≤70 years ( OR = 0.139 , p = 0.005 ) in patients with ischemic stroke after adjusting for confounders . There was no significant difference in death between allopurinol-treated cases ( 3 ; 8.6 % ) and placebo-treated ones ( 6 ; 17.2 % ; p = 0.278 ) . Conclusion : Allopurinol treatment was well tolerated and improved the 3-month functional status of patients with acute ischemic stroke who had high levels of SUA without considering the decreasing effect of allopurinol on SUA Higher levels of serum uric acid are independently associated with endothelial dysfunction , a mechanism for incident hypertension . Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts . However , the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly . In this r and omized , double-blind , placebo-controlled trial of nonhypertensive , overweight , or obese individuals with higher serum uric acid ( body mass index ≥25 kg/m2 and serum uric acid ≥5.0 mg/dL ) , we assigned subjects to probenecid ( 500–1000 mg/d ) , allopurinol ( 300–600 mg/d ) , or matching placebo . The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks . By the end of the trial , 47 , 49 , and 53 participants had been allocated to receive probenecid , allopurinol , and placebo , respectively . Mean serum uric acid levels significantly decreased in the probenecid ( from 6.1 to 3.5 mg/dL ) and allopurinol groups ( from 6.1 to 2.9 mg/dL ) but not in the placebo group ( 6.1 to 5.6 mg/dL ) . None of the interventions produced any significant change in endothelium-dependent vasodilation ( probenecid , 7.4±5.1 % at baseline and 8.3±5.1 % at 8 weeks ; allopurinol , 7.6±6.0 % at baseline and 6.2±4.8 % at 8 weeks ; and placebo , 6.5±3.8 % at baseline and 7.1±4.9 % at 8 weeks ) . In this r and omized , double-blind , placebo-controlled trial , uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals . These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction , a potential mechanism for development of hypertension Background Previous studies of allopurinol and stroke risk have provided contradictory findings , ranging from a protective effect to an increased risk . Our objective was to assess whether allopurinol use is associated with the risk of stroke in the elderly . Methods We used the 5 % r and om sample of Medicare beneficiaries from 2006–2012 to study the association of new allopurinol initiation and incident stroke . We used multivariable-adjusted Cox regression models adjusted for age , gender , race , Charlson index , and cardio-protective medications ( beta-blockers , ACE inhibitors , diuretics , statins ) to calculate hazards ratio ( HR ) with 95 % confidence intervals ( CI ) . Sensitivity analyses adjusted for coronary artery disease ( CAD ) risk factors including hypertension , hyperlipidemia , diabetes , and smoking instead of Charlson index . Results Among 28,488 eligible episodes of incident allopurinol , 2,177 ended in incident stroke ( 7.6 % episodes ) . In multivariable-adjusted analyses , allopurinol use was associated with 9 % lower hazard ratio for stoke , 0.91 ( 95 % CI , 0.83 to 0.99 ) . Compared to no allopurinol use , allopurinol use duration s of 181 days to 2 years , 0.88 ( 95 % CI , 0.78 to 0.99 ) and > 2 years , 0.79 ( 95 % CI , 0.65 to 0.96 ) were significantly associated with lower multivariable-adjusted hazard of stroke . Sensitivity analyses adjusted for CAD risk factors confirmed these findings . In subgroup analyses , significant associations were noted between allopurinol use and the risk of ischemic stroke , 0.89 ( 95 % CI , 0.81 to 0.98 ) ; associations were not significant for hemorrhagic stroke , 1.01 ( 95 % CI , 0.79 to 1.29 ) . Conclusions Allopurinol use is associated with lower risk of stroke overall , more specifically ischemic stroke . This association is evident after 6-months of allopurinol use , and the hazard reduction increases with longer duration of use . Future studies need to examine underlying mechanisms OBJECTIVE The aim of this study was to investigate the long-term effective control of serum uric acid by allopurinol on the carotid intima-media thickness ( IMT ) in patients with type 2 diabetes ( T2DM ) and asymptomatic hyperuricemia ( HUA ) . METHODS This was a r and omized open parallel-controlled study . In this study , 176 patients with T2DM and asymptomatic HUA were r and omly allocated to the conventional or allopurinol treatment groups on the basis of a computer-generated r and om number table . Changes in the carotid IMT , biochemical indexes , high sensitive C-reactive protein ( hs-CRP ) and the incidence of hypertension in patients before and after three years of treatment were examined and compared between the groups . RESULTS There were no statistically significant differences in the baseline characteristics of the study participants between the two treatment groups ( p>0.05 for all ) . Nevertheless , the serum uric acid , triglyceride , and hs-CRP levels and the homeostasis assessment for insulin resistance ( HOMA-IR ) , systolic blood pressure , diastolic blood pressure and the carotid IMT in the allopurinol group were significantly lower than those in the conventional group after three years of treatment ( p<0.01 for all ) . The intention-to-treat analysis indicated that the incidence of new-onset hypertension in the allopurinol group showed a declining trend compared to that in the conventional treatment group ( 6.8 % vs. 13.6 % , p>0.05 ) . CONCLUSION The long-term effective control of serum uric acid by allopurinol may improve insulin resistance , decrease the serum levels of hs-CRP , reduce the carotid IMT , and may delay the development of atherosclerosis in patients with T2DM and asymptomatic HUA Background Previous observational studies that have examined the association of allopurinol with myocardial infa rct ion ( MI ) have provided contradictory results . One study showed that allopurinol reduced the risk , while another study showed an increased risk with allopurinol . Therefore , our objective was to assess whether allopurinol use is associated with a reduction in the risk of MI in the elderly . Method We used the 2006–2012 5 % r and om sample of Medicare beneficiaries to study the association of new allopurinol initiation and the risk of incident MI in a cohort study . Multivariable-adjusted Cox regression models adjusted for age , gender , race , and Charlson index , in addition to various cardio-protective medications ( beta-blockers , angiotensin-converting enzyme ( ACE ) inhibitors , diuretics , statins ) . We calculated hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) . Sensitivity analyses adjusted for coronary artery disease ( CAD ) risk factors , including hypertension , hyperlipidemia , diabetes , and smoking . Results Of the 29,298 episodes of incident allopurinol use , 1544 were associated with incident MI ( 5.3 % episodes ) . Allopurinol use was associated with reduced hazards of MI , with a HR of 0.85 ( 95 % CI , 0.77 to 0.95 ) . Compared to no allopurinol use , longer duration s of allopurinol use were associated with a lower HR of MI : 1–180 days , 0.98 ( 95 % CI , 0.84 to 1.14 ) ; 181 days to 2 years , 0.83 ( 95 % CI , 0.72 to 0.95 ) ; and > 2 years , 0.70 ( 95 % CI , 0.56 to 0.88 ) . Other factors associated with a higher hazard of MI were : age 75 to < 85 years and ≥85 years , male gender , higher Charlson index score , and the use of an ACE inhibitor . Adjustment for CAD risk factors confirmed these findings . Conclusion Incident allopurinol use was associated with a reduction in the risk of incident MI in the elderly . Longer duration s of allopurinol use reduced the risk of incident MI incrementally . Future studies should assess the underlying mechanisms for MI prevention and assess the risk-benefit ratio for allopurinol use OBJECTIVE To investigate the therapeutic effect of allopurinol treatment on acute coronary syndrome and to eluci date its possible mechanism . METHODS Patients with acute coronary syndrome ( n = 100 ) were recruited as research subjects in our hospital . The patients were r and omly divided into two groups , an allopurinol group ( n = 50 ) and a control group ( n = 50 ) . These two groups were treated with conventional antiplatelet , anticoagulation and anti-ischemic therapy ; allopurinol therapy was added to the allopurinol group based on conventional treatment indications . Biochemical markers such as serum creatinine , uric acid , BNP , blood glucose and blood lipid were compared between the two groups . Indicators of oxidative stress and inflammatory response ( MDA , OX-LDL , NO , hs-CRP and TNF-α ) , as well as cardiovascular events during 2-years follow-up , were recorded . RESULTS On admission , there was no difference in serum creatinine , uric acid , BNP , blood glucose or lipid levels between the two groups ( P > 0.05 ) . However , after 1 month of treatment , these levels were improved in patients in the allopurinol group compared to the control group ( P < 0.05 ) . MDA , OX-LDL , hs-CRP and TNF-α decreased after treatment periods of 14 days and 1 month . They were also decreased at 3 month , 6 month , 1 year , and 2 year follow-up visits . However , data from the allopurinol group demonstrated significantly lower levels than in the control group ( P < 0.05 ) . Additionally , compared with the control group , allopurinol treatment significantly elevated the level of NO ( P < 0.05 ) . The total effective rates of the allopurinol group are much higher than in the control group for both angina pectoris ( 93.2 % and 76 % , respectively ) and ECG ( 96 % and 82 % , respectively ) . Most patients in the allopurinol group ( n = 40 ) and the control group ( n = 41 ) received stent implantation with no significant difference shown between them . The incidence of cardiovascular events during 2 years of follow-up in the allopurinol group was 10 % ; it was 30 % in the control group . CONCLUSION Allopurinol has a remarkable effect in the treatment of ACS and can improve the oxidative stress and inflammatory reaction indicators of patients . The protective mechanism of allopurinol might be achieved by suppressing the secretion and release of inflammatory mediators such as TNF-α , hs-CRP , OX-LDL and MDA while increasing levels of NO Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease ( CKD ) , but it is unknown if it has similar effects among patients with CKD . Furthermore , because arterial stiffness increases left ventricular afterload , any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy ( LVH ) . We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in patients with stage 3 CKD and LVH . We r and omly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months ; 53 patients completed the study . We measured left ventricular mass index ( LVMI ) with cardiac magnetic resonance imaging ( MRI ) , assessed endothelial function by flow-mediated dilation ( FMD ) of the brachial artery , and evaluated central arterial stiffness by pulse-wave analysis . Allopurinol significantly reduced LVH ( P=0.036 ) , improved endothelial function ( P=0.009 ) , and improved the central augmentation index ( P=0.015 ) . This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD . Because LVH and endothelial dysfunction associate with prognosis , these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH Background and Purpose — Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke . The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models , reduces oxidative stress in the vasculature , and improves endothelial function . We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke . Methods — We performed a r and omized , double-blind , placebo-controlled trial to investigate the safety , tolerability , and effect of 6 weeks ' treatment with high- ( 300 mg once a day ) or low- ( 100 mg once a day ) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke . Results — We enrolled 50 patients with acute ischemic stroke ( 17 , 17 , and 16 in the high , low , and placebo groups , respectively ) . Mean ( ±SD ) age was 70 ( ±13 ) years . Groups had similar characteristics at baseline . There were no serious adverse events . Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group ( by 0.14 mmol/L at 6 weeks , P=0.002 ) . Intercellular adhesion molecule-1 concentration ( ng/mL ) rose by 51.2 in the placebo group , rose slightly ( by 10.6 ) in the low-dose allopurinol group , but fell in the high-dose group ( by 2.6 ; difference between groups P=0.012 , Kruskal-Wallis test ) . Conclusion — Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke . Uric acid levels were lowered with high doses . These findings support further evaluation of allopurinol as a preventive measure after stroke Fifty-nine patients with primary gout were treated with either a combination of colchicine and allopurinol or colchicine alone . Assessment s of renal function over 2 years revealed a statistically significant fall of glomerular filtration rate an urine concentrating ability in those receiving only colchicine . The renal function of patients given allopurinol did not change . Treatment with allopurinol result ed ina significant reduction of ammonium excretion , a phenomenon which could not be readily explained . Urate clearance also declined during allopurinol treatment , and the impaired urate clearance associated with gout became more evident . The most important observation was that allopurinol retarded an apparent decline of renal function . Presumably this was achieved through its hypouricaemic effect and implies that the hyperuricaemia of gouty patients is deleterious to the kidneys We tested the hypothesis that xanthine oxidase inhibition among African Americans receiving the thiazide-type diuretic chlorthalidone may improve blood pressure control with fewer hyperuricemia-related side effects . We performed a r and omized , double-blind , placebo-controlled study of African Americans with Stage 1 hypertension without clinical ly significant renal disease . One hundred fifty African American men or women between the ages of 18 and 65 years who met the exclusion/ inclusion criteria with untreated or treated hypertension were started on chlorthalidone ( 25 mg/d ) and potassium chloride . After a 5-week run-in on chlorthalidone , baseline testing was performed and they were r and omized to allopurinol ( 300 mg/dL ) or placebo with doses adjusted based on uric acid levels and followed for 8 weeks . One hundred ten subjects completed the study . Baseline systolic blood pressures after the 5-week chlorthalidone run-in were 119.9 ± 13.6 in the allopurinol group and 117 ± 11.2 in the placebo group indicating excellent blood pressure control with the single agent . After at least 4 week postr and omization , the difference in mean change in systolic blood pressure in allopurinol less placebo from visits 5 to 3 was 4.3 mm Hg ( 95 % confidence interval , -0.2 to 8.7 ; P = .059 ) . The difference in mean change in uric acid levels over the same period was 2.1 mg/dL ( 95 % confidence interval , 1.7 - 2.6 ; P < .001 ) . The use of chlorthalidone with or without allopurinol result ed in excellent blood pressure control . The addition of allopurinol tended to improve clinic blood pressure , but the difference from the group receiving chlorthalidone alone was not statistically significant Abstract Background Topiroxostat , a selective xanthine oxidase inhibitor , shows effective reduction in the serum urate level in hyperuricemic patients with or without gout . The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout . Methods The study design was a 22-week , r and omized , multicenter , double-blind study . The enrolled patients were r and omly assigned to treatment with topiroxostat 160 mg/day ( n = 62 ) or to the placebo ( n = 61 ) . The endpoints were the percent change in the serum urate level , change in the estimated glomerular filtration rate , the urinary albumin-to-creatinine ratio , the proportion of patients with serum urate levels of 356.88 μmol/L or less , blood pressure , and serum adiponectin . Results After 22 weeks , although the changes in the estimated glomerular filtration rate and blood pressure were not significant , the percent change in the serum urate level ( −45.38 vs. −0.08 % , P < 0.0001 ) and the percent change in urinary albumin-to-creatinine ratio ( −33.0 vs. −6.0 % , P = 0.0092 ) were found to have decreased in the topiroxostat as compared with the placebo . Although the incidence of ‘ alanine aminotransferase increased ’ was higher in the topiroxostat , serious adverse event rates were similar in the two groups . Conclusion Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout Background : Hyperuricemia has been associated with the development of high blood pressure ( BP ) . We studied the effects of allopurinol therapy in hyperuricemic hemodialysis ( HD ) patients with high BP . Material s and Methods : This single-blind , r and omized cross-over clinical study involved 55 HD patients with serum uric acid level > 6.5 ( men ) and > 5.5 mg/dL ( women ) . They were r and omly divided in two groups , each of which went through two phases . Group-1 in phase-1 received 100 mg/day orally of allopurinol for three months ; while Group-2 was given whatever medication they received prior to the study . After two months of washing period , the groups were crossed-over . The BP levels were measured before and after HD during the eight months study period . Results : Fifty-three patients completed the study ( 33 men and 20 women , with mean age of 55.8 years ) . Uric acid levels decreased significantly during the12 weeks of allopurinol therapy ( 7.71 ± 1.53 to 5.2 ± 1.2 P < 0.005 ) . Overall , after the 12 weeks of allopurinol therapy , systolic and diastolic BP also significantly decreased in allopurinol group , 15.8 % ( 139 to 117 , P < 0.0005 ) and 8.6 % ( 81 to 74 , P < .0005 ) , respectively . There were not significant changes in body mass index , blood urea nitrogen , creatinine , albumin , cholesterol , triglyceride , hemoglobin , liver enzymes and serum electrolytes level after treatment . Patients treated with allopurinol had a significant increase in the quality of dialysis ( KT/V ) ( P : 0.043 ) . Conclusions : In HD patients , allopurinol treatment reduced BP . The results indicate a new potential therapeutic approach for controlling BP in HD patients Topiroxostat , a selective xanthine oxidoreductase inhibitor , is used in Japan for the treatment of hyperuricemic patients with or without gout . In terms of the effectiveness of topiroxostat in lowering serum urate levels , the dose – response relationship has been evaluated ; however , it remains to be verified . A r and omized , multi-center , double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout . During the 16-week study , 157 Japanese hyperuricemic patients with or without gout were r and omly assigned to receive a placebo , topiroxostat at 120 or 160 mg/day , or allopurinol at 200 mg/day . The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration . A dose – response relationship ( regarding decreases in the serum urate levels ) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day . Moreover , at the end of administration , the lowering rate of serum urate levels was determined to be −44.8 % in the topiroxostat 160-mg/day group . No significant difference in the incidence of adverse events was observed among all groups , including the allopurinol group . The serum urate-lowering effect of topiroxostat was found to have a dose – response relationship in Japanese hyperuricemic patients with or without gout Background — Oxidative stress may contribute to heart failure ( HF ) progression . Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes . Methods and Results — We r and omly assigned 253 patients with symptomatic HF , left ventricular ejection fraction ⩽40 % , and serum uric acid levels ≥9.5 mg/dL to receive allopurinol ( target dose , 600 mg daily ) or placebo in a double-blind , multicenter trial . The primary composite end point at 24 weeks was based on survival , worsening HF , and patient global assessment . Secondary end points included change in quality of life , submaximal exercise capacity , and left ventricular ejection fraction . Uric acid levels were significantly reduced with allopurinol in comparison with placebo ( treatment difference , –4.2 [ –4.9 , –3.5 ] mg/dL and –3.5 [ –4.2 , –2.7 ] mg/dL at 12 and 24 weeks , respectively , both P<0.0001 ) . At 24 weeks , there was no significant difference in clinical status between the allopurinol- and placebo-treated patients ( worsened 45 % versus 46 % , unchanged 42 % versus 34 % , improved 13 % versus 19 % , respectively ; P=0.68 ) . At 12 and 24 weeks , there was no significant difference in change in Kansas City Cardiomyopathy Question naire scores or 6-minute walk distances between the 2 groups . At 24 weeks , left ventricular ejection fraction did not change in either group or between groups . Rash occurred more frequently with allopurinol ( 10 % versus 2 % , P=0.01 ) , but there was no difference in serious adverse event rates between the groups ( 20 % versus 15 % , P=0.36 ) . Conclusions — In high-risk HF patients with reduced ejection fraction and elevated uric acid levels , xanthine oxidase inhibition with allopurinol failed to improve clinical status , exercise capacity , quality of life , or left ventricular ejection fraction at 24 weeks . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00987415 Allopurinol lowers blood pressure in adolescents and has other vasoprotective effects . Whether similar benefits occur in older individuals remains unclear . We hypothesized that allopurinol is associated with improved cardiovascular outcomes in older adults with hypertension . Data from the United Kingdom Clinical Research Practice Data link were used . Multivariate Cox-proportional hazard models were applied to estimate hazard ratios for stroke and cardiac events ( defined as myocardial infa rct ion or acute coronary syndrome ) associated with allopurinol use over a 10-year period in adults aged > 65 years with hypertension . A propensity-matched design was used to reduce potential for confounding . Allopurinol exposure was a time-dependent variable and was defined as any exposure and then as high ( ≥300 mg daily ) or low-dose exposure . A total of 2032 allopurinol-exposed patients and 2032 matched nonexposed patients were studied . Allopurinol use was associated with a significantly lower risk of both stroke ( hazard ratio , 0.50 ; 95 % confidence interval , 0.32–0.80 ) and cardiac events ( hazard ratio , 0.61 ; 95 % confidence interval , 0.43–0.87 ) than nonexposed control patients . In exposed patients , high-dose treatment with allopurinol ( n=1052 ) was associated with a significantly lower risk of both stroke ( hazard ratio , 0.58 ; 95 % confidence interval , 0.36–0.94 ) and cardiac events ( hazard ratio , 0.65 ; 95 % confidence interval , 0.46–0.93 ) than low-dose treatment ( n=980 ) . Allopurinol use is associated with lower rates of stroke and cardiac events in older adults with hypertension , particularly at higher doses . Prospect i ve clinical trials are needed to evaluate whether allopurinol improves cardiovascular outcomes in adults with hypertension In this double‐blind cross‐over study allopurinol was found to be no more effective than a placebo in the treatment of psoriasis Introduction Gout affects 2.5 % of the UK 's adult population and is now the most common type of inflammatory arthritis . The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors , such as allopurinol . Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008 . The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol , which has been named the Febuxostat versus Allopurinol Streamlined trial ( FAST ) . Methods and analysis FAST is a cardiovascular safety study using the prospect i ve , r and omised , open , blinded endpoint design . FAST is recruiting in the UK and Denmark . Recruited patients are aged over 60 years , prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor . After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism ( EULAR ) urate targets ( serum urate < 357 µmol/L ) , patients are r and omised to either continue optimal dose allopurinol or to use febuxostat . Patients are followed-up for an average of 3 years . The primary endpoint is first occurrence of the Anti-Platelet Trialists ’ Collaboration ( APTC ) cardiovascular endpoint of non-fatal myocardial infa rct ion , non-fatal stroke or cardiovascular death . Secondary endpoints are all cause mortality and hospitalisations for heart failure , unstable , new or worsening angina , coronary or cerebral revascularisation , transient ischaemic attack , non-fatal cardiac arrest , venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia . The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3 . Ethics and dissemination FAST ( IS RCT N72443728 ) has ethical approval in the UK and Denmark , and results will be published in a peer review ed journal . Trial Registration number FAST is registered in the EU Clinical Trials Register ( EUDRACT No : 2011 - 001883 - 23 ) and International St and ard R and omised Controlled Trial Number Register ( IS RCT N No : IS RCT N72443728 ) BACKGROUND AND OBJECTIVES Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease . Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease . We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction , BP , estimated GFR ( eGFR ) , and inflammatory markers . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month r and omized prospect i ve study . Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups . Flow-mediated dilation ( FMD ) , eGFR , ambulatory BP monitoring , spot urine protein-creatine ratio , and highly sensitive C-reactive protein were measured at baseline and at 4 months . RESULTS Age , gender , lipid profile , eGFR , hemoglobin , glucose , and level of proteinuria were similar in hyperuricemic subjects and controls at baseline . As expected , hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients . Allopurinol treatment result ed in a decrease in serum uric acid , a decrease in systolic BP , an increase in FMD , and an increase in eGFR compared with baseline . No significant difference was observed in the control hyperuricemic and normouricemic groups . In a multiple regression analysis , FMD levels were independently related to uric acid both before ( beta = -0.55 ) and after ( beta = -0.40 ) treatment . CONCLUSIONS Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia Background Hyperuricemia is associated with the onset of chronic kidney disease ( CKD ) and renal disease progression . Febuxostat , a novel , non-purine , selective xanthine oxidase inhibitor , has been reported to have a stronger effect on hyperuricemia than conventional therapy with allopurinol . However , few data are available regarding the clinical effect of febuxostat in patients with CKD . Methods A prospect i ve , r and omized , open-label , parallel-group trial was conducted in hyperuricemic patients with stage 3 CKD . Patients were r and omly assigned to treatment with febuxostat ( n = 21 ) or to continue conventional therapy ( n = 19 ) . Treatment was continued for 12 weeks . The efficacy of febuxostat was determined by monitoring serum uric acid ( UA ) levels , blood pressures , renal function , and urinary protein levels . In addition , urinary liver-type fatty acid-binding protein ( L-FABP ) , urinary albumin , urinary beta 2 microglobulin ( β2MG ) , and serum high sensitivity C-reactive protein were measured before and 12 weeks after febuxostat was added to the treatment . Results Febuxostat result ed in a significantly greater reduction in serum UA ( −2.2 mg/dL ) than conventional therapy ( −0.3 mg/dL , P < 0.001 ) . Serum creatinine and estimated glomerular filtration rate changed little during the study period in each group . However , treatment with febuxostat for 12 weeks reduced the urinary levels of L-FABP , albumin , and β2MG , whereas the levels of these markers did not change in the control group . Conclusion Febuxostat reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD . Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD Abstract We prospect ively evaluated whether an effective 12-month uric acid-lowering therapy ( ULT ) with the available xanthine oxidase ( XO ) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and /or vascular function . Patients with chronic tophaceous gout who did not receive active ULT were included . After clinical evaluation , serum uric acid levels ( SUA ) and markers of oxidative stress were measured , and carotid – femoral pulse wave velocity ( cfPWV ) was assessed . Patients were then treated with allopurinol ( n = 9 ) or with febuxostat ( n = 8) to target a SUA level ≤360 μmol/L. After 1 year treatment , the SUA levels , markers of oxidative stress and the cfPWV were measured again . Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function ( estimated glomerular filtration rate < 60 ml/min ) in the febuxostat group . Uric acid lowering with either inhibitors of XO result ed in almost equally effective reduction in SUA levels . The both treatment groups did not differ in their baseline cfPWV ( allopurinol group : 14.1 ± 3.4 m/s , febuxostat group : 13.7 ± 2.7 m/s , p = 0.80 ) . However , after 1 year of therapy , we observed a significant cfPWV increase in the allopurinol group ( 16.8 ± 4.3 m/s , p = 0.001 as compared to baseline ) , but not in the febuxostat patients ( 13.3 ± 2.3 m/s , p = 0.55 ) . Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout . However , we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening . Since cardiovascular events are an important issue in treating patients with gout , this unexpected finding may have important implication s and should be further investigated in r and omized controlled trials Background Few studies have been conducted that compared lipid levels and uric acid in CKD or End-Stage Renal Disease ( ESRD ) patients with most using animal models . The purpose of the study was to explore effects on lipids while controlling uric acid levels in CKD patients . Methods Twenty-four CKD patients ( N = 24 ) volunteered to participate in this study . The study was conducted using a double-blind , r and omized , placebo controlled experimental protocol . The experimental group was prescribed 300 mg of allopurinol PO daily by their treating physician and followed prospect ively for 8-weeks . The control group consumed a similar pill once a day for 8-weeks . Results ANCOVA revealed significant differences in total cholesterol ( P = 0.009 ) and Apo B ( P = 0.006 ) with lower levels in the allopurinol group . A trend emerged with LDL ( P = 0.052 ) with lower levels in the allopurinol group . No significant differences were discovered in triglycerides ( P = 0.403 ) , HDL ( P = 0.762 ) and total Cholesterol/HDL Ratio ( P = 0.455 ) . Conclusions After statistically controlling for compliance and inflammation significant differences between groups were observed for total cholesterol and Apo B. In both instances the allopurinol group had lower concentrations than the placebo group . Similarly , a trend was observed in LDL with the allopurinol group having lower concentrations than the placebo group BACKGROUND Pouchitis is the major long-term complication of restorative proctocolectomy for ulcerative colitis ( UC ) . Allopurinol is a scavenger of oxygen-derived free radicals , which it is suggested play a role in the development of UC and pouchitis . The first aim was to test the hypothesis that the incidence of pouchitis can be reduced by prophylactic Allopurinol , and secondly to evaluate if Allopurinol influences the overall pouch function . METHODS 273 patients with UC who were planned for proctocolectomy and ileal pouch-anal anastomosis at 12 centres in Sweden between October 1994 and June 1997 were offered the opportunity to participate . 184 patients ( 67 % ) were r and omized to receive postoperative prophylactic Allopurinol 100 mg twice daily or placebo . All 273 patients had clinical and endoscopic follow-up at 1 , 3 , 6 , 12 , 18 , 24 months after surgery . RESULTS Of the 184 r and omized patients , 94 were r and omized to Allopurinol and 90 to placebo ; 116 patients ( 63 % ) completed follow-up and the crude incidence of pouchitis among those patients fullfilling the protocol was 31 % in the Allopurinol group and 28 % in the placebo group ( ns ) . The cumulative risk for a first attack of pouchitis was 30 % and 26 % after 24 months ( ns ) . The overall pouch function improved over time and did not differ significantly between the two groups . CONCLUSIONS Prophylactic Allopurinol did not reduce the risk of a first attack of pouchitis BACKGROUND Hyperuricemia is associated strongly with the development of hypertension , renal disease , and progression . Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase . We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients . METHODS We conducted a prospect i ve , r and omized , controlled trial of 54 hyperuricemic patients with chronic kidney disease . Patients were r and omly assigned to treatment with allopurinol , 100 to 300 mg/d , or to continue the usual therapy for 12 months . Clinical , hematologic , and biochemical parameters were measured at baseline and 3 , 6 , and 12 months of treatment . We define our study end points as : ( 1 ) stable kidney function with less than 40 % increase in serum creatinine level , ( 2 ) impaired renal function with creatinine level increase greater than 40 % of baseline value , ( 3 ) initiation of dialysis therapy , and ( 4 ) death . RESULTS One patient in the treatment group dropped out because of skin allergy to allopurinol . Serum uric acid levels were significantly decreased in subjects treated with allopurinol , from 9.75 + /- 1.18 mg/dL ( 0.58 + /- 0.07 mmol/L ) to 5.88 + /- 1.01 mg/dL ( 0.35 + /- 0.06 mmol/L ; P < 0.001 ) . There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups . There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy , although it did not reach statistical significance ( P = 0.08 ) . Overall , 4 of 25 patients ( 16 % ) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients ( 46.1 % ) in the control group ( P = 0.015 ) . CONCLUSION Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease . Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls . Results of this study need to be confirmed with an additional prospect i ve trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease sub population Inflammation and oxidative stress play a crucial role in the development of colorectal cancer ( CRC ) and interference with these mechanisms represents a strategy in CRC chemoprevention . Allopurinol , a safe molecular scavenger largely used as antigout agent , has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies . We conducted a r and omized , double-blind , placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis . After complete colonoscopy and biopsy of the index polyp , 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol ( 100 mg or 300 mg ) and treated for four weeks before polyp removal . Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint . Secondary endpoints were the immunohistochemical ( IHC ) expression of NF-κB , β-catenin , topoisomerase-II-α , and terminal deoxynucleotidyl transferase – mediated dUTP nick end labeling ( TUNEL ) in adenomatous polyps and normal adjacent colonic tissue . Compared with placebo , Ki-67 levels were not significantly modulated by allopurinol , whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue , with a mean change from baseline of −10.6 % , 95 % confidence interval ( CI ) , −20.5 to −0.7 , and −8.1 % , 95 % CI , −22.7 to 6.5 , respectively . NF-κB also decreased significantly in normal adjacent tissue ( −16.4 % ; 95 % CI , −29.0 to −3.8 ) . No dose – response relationship was noted , except for NF-κB expression in normal tissue . Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue . Further studies should define its potential chemopreventive activity . Cancer Prev Res ; 6(2 ) ; 74–81 . © 2012 AACR OBJECTIVE The therapeutics for bipolar disorders are still far from adequate , and new options with improved effectiveness , safety , and tolerability in a wide range of patients are necessary . Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders . This study aim ed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania . METHOD A r and omized , placebo-controlled , double-blind study was performed in adult in patients ( N = 180 ) with a DSM-IV-TR diagnosis of bipolar I disorder , current episode manic with or without psychotic features ( rapid cyclers and mixed episodes were not included ) . No antipsychotic agent was used during the study . Subjects were given fixed oral doses of either allopurinol 600 mg/day ( N = 60 ) , dipyridamole 200 mg/day ( N = 60 ) , or placebo ( N = 60 ) added to lithium for 4 weeks . Subjects were rated at baseline and days 7 , 14 , 21 , and 28 using the Young Mania Rating Scale ( YMRS ) as the primary efficacy measure . The study was conducted between September 2003 and September 2006 . RESULTS Allopurinol result ed in greater mean reductions in YMRS scores from baseline to day 21 ( p < .001 ) and day 28 ( p = .003 ) compared with placebo using a linear model analysis ( d = 0.32 , 95 % CI = 0.07 to 0.57 ) . Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo ( p = .008 ) . Lithium showed a significant antimanic efficacy even in the placebo group . Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group ( p < .001 ) . CONCLUSION Allopurinol is clinical ly effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania , especially for those presenting tolerability and safety issues with antipsychotics . The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder . Further placebo-controlled studies with allo-purinol compared with st and ard mood stabilizers in mania and maintenance are warranted . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00560079 Background : In observational studies , higher uric acid levels are associated with metabolic syndrome , diabetes , and kidney disease . Objective : The objective of this study is to examine whether reduction of plasma uric acid with febuxostat , a xanthine oxido reductase inhibitor , impacts adipose tissue oxidative stress , adipokines , and markers of systemic inflammation or kidney fibrosis . Design : This was a double-blinded r and omized controlled trial . Setting : Academic university setting was used . Patients : Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included . Measurements : Adipose tissue thiobarbituric acid reducing substances ( TBARS ) and adiponectin concentrations and urinary transforming growth factor – β ( TGF-β ) were primary endpoints . Plasma C-reactive protein , high molecular weight – adiponectin , interleukin–6 , tumor necrosis factor – α , and TBARS and albuminuria were among predefined secondary endpoints . Methods : Participants were r and omly assigned to febuxostat ( n = 40 ) or matching placebo ( n = 40 ) and followed for 24 weeks . Results : Baseline plasma uric acid levels were 426 ± 83 µmol/L ; 95 % completed the study . Estimated glomerular filtration rate ( eGFR ) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks ( P = .05 ) . In separate mixed-effects models , compared with placebo , febuxostat reduced uric acid by 50 % ( P < .001 ) but had no significant effects on subcutaneous adipose tissue TBARS ( −7.4 % , 95 % confidence interval [ CI ] , 57.4%-101.4 % ) or adiponectin ( 6.7 % , 95 % CI , 26.0%-53.8 % ) levels or urinary TGF-β/creatinine ratio ( 18.0 % , 95 % CI , 10.0%-54.8 % ) or secondary endpoints . Limitations : Relatively modest sample size and short duration of follow-up . Conclusions : In this population with progressive diabetic nephropathy , febuxostat effectively reduced plasma uric acid . However , no detectable effects were observed for the prespecified primary or secondary endpoints . Trial Registration : The study was registered in clinical trials.gov ( NCT01350388 ) Objectives To evaluate the efficacy and tolerability of st and ardized aqueous extracts of Terminalia chebula and Terminalia bellerica versus febuxostat and placebo on reduction in serum uric acid levels in subjects with hyperuricemia . Material s and methods A total of 110 eligible subjects with hyperuricemia were enrolled and r and omized to either of the five treatment groups – T. chebula 500 mg twice a day ( BID ) , T. bellerica 250 mg BID , T. bellerica 500 mg BID , placebo BID , and febuxostat 40 mg once daily plus an identical placebo – for a duration of 24 weeks . Serum uric acid levels were measured at baseline and at the end of 4 , 8 , 12 , 16 , 20 , and 24 weeks . Statistical analysis was done using GraphPad Prism Software 4 . Results and interpretation All active treatment groups showed a reduction in serum uric acid levels compared to baseline and placebo . Significant reduction in mean serum uric acid levels started as early as 4 weeks following treatment , compared to baseline , with T. bellerica ( 500 and 250 mg ) , febuxostat ( P<0.001 ) , and T. chebula 500 mg ( P<0.01 ) ; an increase in serum uric acid levels was seen with placebo ( P<0.05 ) . The serum uric acid levels became steady after 16 weeks of treatment and remained the same until the end of 24 weeks . The reduction of serum uric acid levels in the T. bellerica 500 mg group was nearly twice that of the T. chebula 500 mg group as well as T. bellerica 250 mg group at all time points . T. bellerica 500 mg reduced serum uric acid levels from 8.07±0.87 to 5.78±0.25 compared to febuxostat , which reduced serum uric acid levels from 8.53±0.97 to 4.28±0.67 ( P<0.001 ) at the end of 24 weeks . The efficacy of T. bellerica appeared to be dose dependent . All the formulations were well tolerated . Conclusion T. bellerica has the potential for treating hyperuricemia as it was devoid of any serious adverse effects in the present study . Further studies are needed to confirm this potential Background — Allopurinol has been shown to improve endothelial function in chronic heart failure . This study aim ed to establish its mechanism of action and to construct a dose – response curve for the effect of allopurinol . Methods and Results — Two r and omized , placebo-controlled , double-blind , crossover studies were performed for 1 month on patients with New York Heart Association Class II – III chronic heart failure , comparing 300 mg allopurinol , 600 mg allopurinol , and placebo for the first study and 1000 mg probenecid versus placebo in the second study . Endothelial function was assessed by st and ard forearm venous occlusion plethysmography . Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo ( % change in forearm blood flow [ mean±SEM ] : 240.31±38.19 % versus 152.10±18.21 % versus 73.96±10.29 % , P<0.001 ) . For similar levels of urate lowering , the uricosuric agent probenecid had no effect on endothelial function . Sodium nitroprusside response was unchanged by all treatments . Vitamin C and acetylcholine coinfusion data showed that 600 mg/d allopurinol completely abolished the oxidative stress that was sensitive to high-dose vitamin C. Conclusions — For the first time , we have shown that a steep dose – response relationship exists between allopurinol and its effect on endothelial function . We also showed that the mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction . The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study Summary Background Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume . If such an effect also occurs in man , this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris . We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina . Methods 65 patients ( aged 18–85 years ) with angiographically documented coronary artery disease , a positive exercise tolerance test , and stable chronic angina pectoris ( for at least 2 months ) were recruited into a double-blind , r and omised , placebo-controlled , crossover study in a hospital and two infirmaries in the UK . We used computer-generated r and omisation to assign patients to allopurinol ( 600 mg per day ) or placebo for 6 weeks before crossover . Our primary endpoint was the time to ST depression , and the secondary endpoints were total exercise time and time to chest pain . We did a completed case analysis . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 82040078 . Findings In the first treatment period , 31 patients were allocated to allopurinol and 28 were analysed , and 34 were allocated to placebo and 32 were analysed . In the second period , all 60 patients were analysed . Allopurinol increased the median time to ST depression to 298 s ( IQR 211–408 ) from a baseline of 232 s ( 182–380 ) , and placebo increased it to 249 s ( 200–375 ; p=0·0002 ) . The point estimate ( absolute difference between allopurinol and placebo ) was 43 s ( 95 % CI 31–58 ) . Allopurinol increased median total exercise time to 393 s ( IQR 280–519 ) from a baseline of 301 s ( 251–447 ) , and placebo increased it to 307 s ( 232–430 ; p=0·0003 ) ; the point estimate was 58 s ( 95 % CI 45–77 ) . Allopurinol increased the time to chest pain from a baseline of 234 s ( IQR 189–382 ) to 304 s ( 222–421 ) , and placebo increased it to 272 s ( 200–380 ; p=0·001 ) ; the point estimate was 38 s ( 95 % CI 17–55 ) . No adverse effects of treatment were reported . Interpretation Allopurinol seems to be a useful , inexpensive , well tolerated , and safe anti-ischaemic drug for patients with angina . Funding British Heart Foundation Objectives To quantify the risk of non-fatal acute myocardial infa rct ion ( AMI ) among users of allopurinol . Methods We carried out a population -based case – control study over the period 2001–2007 in patients aged 40–90 years . Patients who had prescriptions of allopurinol or an episode of AMI before the start date of follow-up were excluded from the main analysis . Allopurinol initiators were classified as current users if their last prescription ended in the 30-day window before the recorded date of AMI for cases and a r and om date for controls . The association between use of allopurinol and non-fatal AMI was measured through an OR and adjusted for confounding factors by an unconditional logistic regression . Results We identified 3171 cases of non-fatal AMI and 18 525 controls . Cases had a lower prevalence of current use of allopurinol ( 0.82 % ) than controls ( 1.03 % ) , yielding to an OR of 0.52 ( 95 % CI 0.33 to 0.83 ) . The decreased risk was driven by men ( OR in men=0.44 ; 95 % CI 0.25 to 0.76 ; OR in women=0.90 ; 0.36 to 2.23 ) . No difference by age was observed . The effect was only observed at higher doses ( 300 mg or greater OR=0.30 ; 0.13 to 0.72 ; < 300 mg OR=0.67 ; 0.37 to 1.23 ) and with prolonged treatments ( < 31 days , OR=1.12 ( 0.55 to 2.29 ) ; 31–180 days , OR=0.61 ; 0.29 to 1.29 ; > 180 days OR=0.21 ; 0.08 to 0.53 ; p for trend=0.001 ) . Among those with a previous AMI , allopurinol use also showed a significant reduced risk of recurrence ( OR=0.16 ; 0.04 to 0.76 ) . Conclusions The present study supports the hypothesis that allopurinol is associated with a reduced risk of non-fatal AMI , which seems to be dose-dependent and duration -dependent BACKGROUND Increased oxidative stress in heart failure ( HF ) leads to inflammation and endothelial dysfunction ( ED ) . Both statins and allopurinol have known anti-oxidant properties , but their utility in HF has not been fully assessed . METHODS This investigation was a prospect i ve , double-blind , double-dummy study , performed between March 2007 and June 2009 . Seventy-four HF patients , with New York Heart Association ( NYHA ) Class II or III status and left ventricular ejection fraction ( LVEF ) < 40 % , were included . Patients received placebo during 4 weeks and were then r and omized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo ( ATV+PLA group ) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally ( ATV+ALLO group ) . Malondialdehyde ( MDA ) , extracellular superoxide dismutase ( ecSOD ) activity and uric acid ( UA ) levels , among others , were determined at baseline and after 4 weeks of treatment . ED was assessed by flow-dependent endothelial-mediated vasodilation ( FDD ) , and functional capacity by 6-minute walk test ( 6MWT ) . RESULTS Thirty-two patients were r and omized to ATV+PLA and 38 to ATV+ALLO . Mean age was 59 ± 2 years , 82 % were male , and 22 % had an ischemic etiology . Hypertension was present in 60 % and diabetes in 15 % of those studied . No significant differences were observed between baseline measurements and after placebo . After 4 weeks of treatment , both groups showed a significant decrease on MDA ( 0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 μmol/liter , p = 0.88 ) , UA ( 7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl , p < 0.01 ) and FDD ( 3.9 ± 0.2 % to 5.6 ± 0.4 % and 4.6 ± 0.3 % to 7.1 ± 0.5 % , p = 0.07 ) with increased ecSOD activity ( 109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16 , U/ml/min , p = 0.41 ) and improved 6MWT ( 447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m , p = 0.83 ) , with all values for ATV+PLA and ATV+ALLO , respectively ; p-values are for comparison between groups after treatment . CONCLUSION Short-term ATV treatment in heart failure ( HF ) patients reduces oxidative stress and improves FDD and functional capacity . These beneficial effects are not strengthened by the addition of allopurinol OBJECTIVE Allopurinol , a hypouricemic agent , has been shown to present therapeutic effects in mania associated with hyperuricemia . This study assessed the efficacy and safety of risperidone as an adjunctive agent to lithium and haloperidol for the treatment of acute mania in hospitalized bipolar patients . METHODS Eighty-two patients aged between 18 and 49 were eligible to participate , as they met the DSM-IV criteria for a current manic episode , on the basis of a clinical interview by two academician psychiatrists . In addition , a score of at least 20 points on the Young Mania Rating Scale was required representing at least a moderate-to-severe mania . Forty-one patients were r and omly allocated to lithium ( 1 - 1.2 mEq/L ) + haloperidol ( 10 mg/day ) + allopurinol ( 300 mg/day ) ( group A ) or lithium ( 1 - 1.2 mEq/L ) + haloperidol ( 10 mg/day ) + placebo ( group B ) for an 8-week , double-blind , placebo-controlled study . Patients were assessed by a third-year resident of psychiatry at baseline and at 7 , 14 , 28 , 42 , and 56 days after the medication started . The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment . The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale ( ESRS ) . Side effects were systematic ally recorded throughout the study and were assessed using a checklist . RESULTS Young Mania Rating Scale scores improved with allopurinol . The difference between the two protocol s was significant as indicated by the effect of the group , the between-subjects factor ( F = 5.22 , df = 1 , p = 0.008 ) . The mean ESRS scores for the placebo group were higher than the allopurinol group . However , the differences were not significant over the trial . The difference between the two groups in the frequency of side effects was not significant except for agitation that was more often in the placebo group . CONCLUSIONS The efficacy of allopurinol to obtain a greater improvement in patients with mania seems to support the purinergic dysfunction in mania BACKGROUND Allopurinol promotes the salvage of purines , possibly increasing endogenous adenosine levels . Recent studies suggest that adenosine has neuroprotective and inhibitory effects . Two previous inpatient trials demonstrated that allopurinol has anti-manic activity . Our objective was to test allopurinol as an adjunct to st and ard medications in bipolar disorder manic out patients . METHODS In this double-blind , placebo-controlled trial , 27 subjects who met DSM-IV criteria for bipolar disorder and scored ≥ 14 on the Young Mania Rating Scale ( YMRS ) were r and omized to augmentation with allopurinol or placebo for six weeks . The primary efficacy measure was the YMRS . The primary safety measure was the Treatment Emergent Symptom Scale . RESULTS The effect of allopurinol augmentation in decreasing mean YMRS scores was modest , with an overall effect size of -0.25 ( Cohen 's d ) . Allopurinol-treated individuals who abstained from caffeine ( n = 4 ) had a greater decrease in YMRS scores ( -15.3 ± 1.8 ) than subjects using caffeine ( n = 5 ) ( -9.6 ± 3.4 , p = 0.219 ) , with an effect size of -0.86 . CONCLUSION In this small outpatient pilot study , allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms . Subjects with restricted caffeine use showed a greater effect size compared to caffeine users . This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol 's anti-manic effect in previous studies INTRODUCTION Diabetic nephropathy is the most prevalent cause of end-stage renal disease . Besides factors such as angiotensin II , cytokines , and vascular endothelial growth factor , uric acid may play a role as the underlying cause of diabetic nephropathy . We evaluated allopurinol effects on proteinuria in diabetic patients with nephropathy . MATERIAL S AND METHODS In a double-blinded r and omized controlled trial on 40 patients with type 2 diabetes mellitus and diabetic nephropathy ( proteinuria , at least 500 mg/24 h and a serum creatinine level less than 3 mg/dL ) , allopurinol ( 100 mg/d ) was compared with placebo . Administration of antihypertensive and renoprotective drugs ( angiotensin-converting enzyme inhibitors and angiotensin receptor blockers continued for both groups , without changes in dosage . Proteinuria was compared at baseline and 2 and 4 months between the two groups . RESULTS Each group consisted of 9 men and 11 women . There were no difference between two groups regarding age , body mass index , duration of diabetes mellitus , systolic and diastolic blood pressure , fasting blood glucose , blood urea nitrogen , serum creatinine , serum potassium , and urine volume . Serum levels of uric acid ( P = .02 ) and 24-hour urine protein ( P = .049 ) were significantly lower in the patients on allopurinol , after 4 months of receiving allopurinol , compared with the control group . CONCLUSIONS Low-dose allopurinol can reduce severity of proteinuria after 4 months of drug administration , which is probably due to decreasing the serum level of uric acid . Thus , allopurinol can be administered as an adjuvant cost-effective therapy for patients with diabetic nephropathy In a double-blind study , we examined the efficacy of allopurinol in the prevention of recurrent calcium oxalate calculi of the kidney . Sixty patients with hyperuricosuria and normocalciuria who had a history of calculi were r and omly assigned to receive either allopurinol ( 100 mg three times daily ) or a placebo . After the study , the placebo group had 63.4 percent fewer calculi ( P less than 0.001 ) , whereas the allopurinol group had 81.2 percent fewer calculi ( P less than 0.001 ) . During the study period , the mean rate of calculous events was 0.26 per patient per year in the placebo group and 0.12 in the allopurinol group . When the treatment groups were compared by actuarial analysis , the allopurinol group was found to have a significantly longer time before recurrence of calculi ( P less than 0.02 ) . We conclude that allopurinol is effective in the prevention of calcium oxalate stones in patients with hyperuricosuria . The large reduction in the frequency of calculi in the placebo group underscores the positive treatment bias that regularly occurs in trials of prophylaxis against renal calculi when historical controls are used BACKGROUND Asymptomatic hyperuricemia increases renal and cardiovascular ( CV ) risk . We previously conducted a 2-year , single-blind , r and omized , controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk . STUDY DESIGN Post hoc analysis of a long-term follow-up after completion of the 2-year trial . SETTING & PARTICIPANTS 113 participants ( 57 in the allopurinol group and 56 in the control group ) initially followed up for 2 years and 107 participants followed up to 5 additional years . INTERVENTION Continuation of allopurinol treatment , 100mg/d , or st and ard treatment . OUTCOME Renal event ( defined as starting dialysis therapy and /or doubling serum creatinine and /or ≥50 % decrease in estimated estimated glomerular filtration rate ) and CV events ( defined as myocardial infa rct ion , coronary revascularization or angina pectoris , congestive heart failure , cerebrovascular disease , and peripheral vascular disease ) . RESULTS During initial follow-up , there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group . In the long-term follow-up period , 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol . During long-term follow-up , an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event , respectively , and an additional 18 and 8 participants in the control group experienced a renal or CV event , respectively . Thus , during the initial and long-term follow-up ( median , 84 months ) , 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group ( HR , 0.32 ; 95 % CI , 0.15 - 0.69 ; P=0.004 ; adjusted for age , sex , baseline kidney function , uric acid level , and renin-angiotensin-aldosterone system blockers ) . Overall , 16 patients treated with allopurinol experienced CV events compared with 23 in the control group ( HR , 0.43 ; 95 % CI , 0.21 - 0.88 ; P=0.02 ; adjusted for age , sex , and baseline kidney function ) . LIMITATIONS Small sample size , single center , not double blind , post hoc follow-up and analysis . CONCLUSIONS Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients . Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction . This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia . We r and omly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat ( 10 mg daily ) group and a control group and measured flow-mediated dilation , serum uric acid ( UA ) levels , systolic and diastolic blood pressure , malondialdehyde-modified low-density lipoprotein ( MDA-LDL ) , and highly sensitive C-reactive protein ( hsCRP ) at baseline and at the end of a 4-week study period . Flow-mediated dilation increased from 5.3 % ± 2.4 % to 8.9 % ± 3.6 % in the febuxostat group but did not change significantly in the control group . Treatment with febuxostat result ed in a significant decrease in serum UA level and a significant decrease in MDA-LDL compared with baseline , but no significant difference was observed in hsCRP level or blood pressure . No significant differences were observed in the control group . Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia Background : Hyperuricemia is an independent risk factor for renal progression in IgA nephropathy ( IgAN ) . However , no study has evaluated the effect of allopurinol on the clinical outcome in hyperuricemic IgAN . Methods : First , a retrospective cohort study of 353 IgAN patients was conducted to explore the relationship between uric acid ( UA ) and the progression of renal disease over a mean period of 5 years . Then , 40 hyperuricemic IgAN patients were r and omized to receive allopurinol ( 100–300 mg/day ) or usual therapy for 6 months . The study outcomes were renal disease progression and /or blood pressure . Results : Hyperuricemia independently predicted renal survival at 1 , 3 , and 5 years after adjustment for different baseline estimated glomerular filtration rates . In the r and omized controlled trial , allopurinol did not significantly alter renal progression or proteinuria . The antihypertensive drug dosage was reduced in 7 of 9 cases with hypertension in the allopurinol group compared to 0 of 9 cases in the control group ( p < 0.01 ) . UA levels correlated with mean arterial pressure in normotensive patients ( r = 0.388 , p < 0.001 ) . Conclusion : Hyperuricemia predicts the progression of IgAN independently of baseline estimated glomerular filtration rate . Allopurinol may improve the control of blood pressure . Further studies are required to explore the effects of lowering UA on renal protection in IgAN BACKGROUND AND OBJECTIVES Hyperuricemia is associated with hypertension , inflammation , renal disease progression , and cardiovascular disease . However , no data are available regarding the effect of allopurinol in patients with chronic kidney disease . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We conducted a prospect i ve , r and omized trial of 113 patients with estimated GFR ( eGFR ) < 60 ml/min . Patients were r and omly assigned to treatment with allopurinol 100 mg/d ( n = 57 ) or to continue the usual therapy ( n = 56 ) . Clinical , biochemical , and inflammatory parameters were measured at baseline and at 6 , 12 , and 24 months of treatment . The objectives of study were : ( 1 ) renal disease progression ; ( 2 ) cardiovascular events ; and ( 3 ) hospitalizations of any causes . RESULTS Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol . In the control group , eGFR decreased 3.3 + /- 1.2 ml/min per 1.73 m(2 ) , and in the allopurinol group , eGFR increased 1.3 + /- 1.3 ml/min per 1.73 m(2 ) after 24 months . Allopurinol treatment slowed down renal disease progression independently of age , gender , diabetes , C-reactive protein , albuminuria , and renin-angiotensin system blockers use . After a mean follow-up time of 23.4 + /- 7.8 months , 22 patients suffered a cardiovascular event . Diabetes mellitus , previous coronary heart disease , and C-reactive protein levels increased cardiovascular risk . Allopurinol treatment reduces risk of cardiovascular events in 71 % compared with st and ard therapy . CONCLUSIONS Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease . In addition , allopurinol reduces cardiovascular and hospitalization risk in these subjects Objective Central blood pressure ( CBP ) and carotid intima-media thickness ( CIMT ) are surrogate measures of cardiovascular risk . Allopurinol reduces serum uric acid and oxidative stress and improves endothelial function and may therefore reduce CBP and CIMT progression . This study sought to ascertain whether allopurinol reduces CBP , arterial stiffness and CIMT progression in patients with ischaemic stroke or transient ischaemic attack ( TIA ) . Methods We performed a r and omised , double-blind , placebo-controlled study , examining the effect of 1-year treatment with allopurinol ( 300 mg daily ) , on change in CBP , arterial stiffness and CIMT progression at 1 year and change in endothelial function and circulating inflammatory markers at 6 months . Patients aged over 18 years with recent ischaemic stroke or TIA were eligible . Results Eighty participants were recruited , mean age 67.8 years ( SD 9.4 ) . Systolic CBP [ −6.6 mm Hg ( 95 % CI −13.0 to −0.3 ) , p=0.042 ] and augmentation index [ −4.4 % ( 95 % CI −7.9 to −1.0 ) , p=0.013 ] were each lower following allopurinol treatment compared with placebo at 12 months . Progression in mean common CIMT at 1 year was less in allopurinol-treated patients compared with placebo [ between-group difference [ −0.097 mm ( 95 % CI −0.175 to −0.019 ) , p=0.015 ] . No difference was observed for measures of endothelial function . Conclusions Allopurinol lowered CBP and reduced CIMT progression at 1 year compared with placebo in patients with recent ischaemic stroke and TIA . This extends the evidence of sustained beneficial effects of allopurinol to these prognostically significant outcomes and to the stroke population , highlighting the potential for reduction in cardiovascular events with this treatment strategy . Trial registration number IS RCT N11970568 BACKGROUND Reactive oxygen species ( ROS ) have been linked to hypertrophy , remodeling and abnormal excitation-contraction coupling . Previous data demonstrated that an increase in oxidative stress is associated to the pathogenesis of congestive heart failure ( CHF ) . We examined whether inhibition of the superoxide anion ( * O2(-))-generating enzyme xanthine oxidase ( XO ) with oxypurinol may improve cardiac function in patients with CHF . METHODS AND RESULTS A r and omized , placebo-controlled , double-blind study on 60 patients ( 30/group ) with New York Heart Association class II-III CHF , comparing 600-mg/day oxypurinol during 1 month with placebo , added to st and ard therapy . Effects on left ventricular ejection fraction ( LVEF ) , serum uric acid ( SUA ) level , and 6-minute walking test were analyzed . SUA decreased by 16.0 + /- 2.8 mg/L from baseline to Week 4 in the oxypurinol group relative to placebo ( P < .01 , n = 30 per group ) . LVEF showed an increase of 4.7 + /- 2.6 % from baseline to Week 4 in the oxypurinol group relative to placebo that did not reach statistical significance ( P < .08 ) . When patients with LVEF > 40 % at baseline were excluded , a statistically significant increase of 6.8 + /- 2.8 % from baseline to Week 4 was seen in the oxypurinol group relative to placebo ( P < .02 , n = 26 placebo , n = 21 oxypurinol ) . No treatment-related adverse effects or increase in walking capacity were detected . CONCLUSION Inhibition of XO by oxypurinol in patients with CHF decreases SUA and improves LVEF in patients with LVEF < or = 40 % after 1 month of treatment Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes , but whether it has a causal role in insulin resistance remains controversial . Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance . Methods Subjects with asymptomatic hyperuricemia ( n = 73 ) were prospect ively placed on allopurinol ( n = 40 ) or control ( n = 33 ) for 3 months . An additional control group consisted of 48 normouricemic subjects . Serum uric acid , fasting glucose , fasting insulin , HOMA-IR ( homeostatic model assessment of insulin resistance ) , and high-sensitivity C-reactive protein were measured at baseline and at 3 months . Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose , fasting insulin , and HOMA-IR index , as well as a reduction in serum high-sensitivity C-reactive protein . The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline ( n = 8 [ 20 % ] vs n = 30 [ 75 % ] , 3 months vs baseline , P < 0.001 ) . In the hyperuricemic control group , only glucose decreased significantly and , in the normouricemic control , no end point changed . Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia . Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES A multicenter study with r and omized , placebo-controlled , double-blind , parallel , intergroup comparison was carried out to evaluate the dose-response relationship , efficacy , and safety of febuxostat in 202 patients with hyperuricemia ( including patients with gout ) in Japan . METHODS The subjects were treated with febuxostat at fixed maintenance doses ( 20 - 80 mg/d ) or a placebo for 16 weeks . The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated . RESULTS The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8 % in the 80-mg/d dose group , 83.3 % in the 60-mg/d group , 82.9 % in the 40-mg/d group , 46.5 % in the 20-mg/d group , and 2.6 % in the placebo group ( P < 0.001 , Mantel-Haenszel test ) . A statistically significant dose-response relationship was found . The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d . No deaths , events posing a clinical problem , or serious adverse reactions attributable to febuxostat were noted . Similar results were obtained regardless of gout history . CONCLUSIONS Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80 % or more of patients with hyperuricemia ( including gout ) at doses of 40 mg/d or higher BACKGROUND Febuxostat has been reported to have a stronger effect on hyperuricemia than allopurinol . METHODS AND RESULTS Cardiac surgery patients with hyperuricemia ( n=141 ) were r and omized to a febuxostat group or an allopurinol group . The study was single-blind , so the treatment was not known by the investigators . The primary endpoint was serum uric acid ( UA ) level . Secondary endpoints included serum creatinine , urinary albumin , cystatin-C , oxidized low-density lipoprotein ( LDL ) , eicosapentaenoic acid/arachidonic acid ratio , total cholesterol , triglycerides , LDL , high-density lipoprotein , high-sensitivity C-reactive protein , blood pressure , heart rate , pulse wave velocity ( PWV ) , ejection fraction , left ventricular mass index ( LVMI ) , and adverse reactions . UA level was significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward . Serum creatinine , urinary albumin , cystatin-C and oxidized LDL were also significantly lower in the febuxostat group . There were no significant changes in systolic blood pressure , PWV , and LVMI in the allopurinol group , but these parameters all had a significant decrease in the febuxostat group . CONCLUSIONS Febuxostat was effective for high-risk cardiac surgery patients with hyperuricemia because it reduced UA more markedly than allopurinol . Febuxostat also had a renoprotective effect , inhibited oxidative stress , showed anti-atherogenic activity , reduced blood pressure , and decreased PWV and LVMI WHAT IS KNOWN AND OBJECTIVE In Japan , although topiroxostat , a selective xanthine oxidoreductase inhibitor , has been used for the treatment of patients with hyperuricemia including gout , no published r and omized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported . The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout . METHODS We conducted an exploratory , phase 2a , multicentre , r and omized , double-blind , 8-week , placebo-controlled study in Japanese hyperuricemic patients with or without gout . The study arms were placebo and topiroxostat 40 , 60 , 80 or 120 mg/day . The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit . RESULTS AND DISCUSSION One hundred and eighty-seven eligible patients were r and omized and 186 received at least one dose of the study drug . The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day ( P < 0·001 , Jonckheere-Terpstra test ) . The mean per cent change in serum urate level from baseline at the final visit was -30·8 % in the 120-mg group and 1·6 % with placebo , with a between-group difference of -32·4 % ( [ 95 % confidence interval , -38·9 % to -25·9 % ] ; P < 0·001 ) . Incidences of overall adverse events ( AEs ) in the topiroxostat groups were comparable to those in the placebo group ; however , the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group . The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups . WHAT IS NEW AND CONCLUSIONS A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout . Further clinical studies aim ed at evaluating the long-term safety and clinical efficacy are warranted OBJECTIVE To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia , with the objective of increasing the endogenous pool of purines , including the neuro-modulator adenosine . METHOD A double-blind , placebo-controlled , crossover clinical trial of add-on allopurinol ( 300 mg b.i.d . ) for poorly responsive schizophrenia or schizoaffective disorder ( DSM-IV criteria ) was conducted . Thirty-five patients were enrolled , of whom 22 completed the 12 weeks of the study . Eighteen of these patients also completed a P50 evoked potential evaluation . RESULTS Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative , and general scores , particularly for positive symptoms compared with baseline and with placebo phase . Nine patients improved more than 20 % in PANSS total score during allopurinol treatment , whereas none responded in the placebo phase . Responders had a shorter duration of illness than nonresponders . P50 auditory sensory gating failed to improve with allopurinol treatment . CONCLUSIONS Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia , especially for refractory positive symptoms OBJECTIVE To investigate if adjunctive allopurinol reduces symptoms in schizophrenia out patients with persistent symptoms despite adequate pharmacotherapy . METHOD N=59 schizophrenia out patients were r and omly assigned to receive adjunctive allopurinol 300 mg bid or identical-looking placebo for 8 weeks after a 2-week placebo run-in . Symptoms were assessed biweekly . RESULTS A total of n=51 patients completed the trial . Including all n=59 r and omized patients , a total of 4 of 31 in the allopurinol group and 0 of 28 in the placebo group had at least a 20 % reduction in total PANSS score at the final study visit ( chi-square=3.88 , p=.049 ) . Among the n=51 completers , individuals in the allopurinol group rated themselves as more improved than did those in the placebo group ( z=-2.24 , p=.025 ) . The allopurinol medication was well tolerated and there were not any adverse events attributed to the study medication . CONCLUSIONS Allopurinol may be an effective adjunctive medication for some patients with persistent schizophrenia OBJECTIVE To determine the effects of furosemide on serum urate ( SU ) , plasma oxypurinol and urinary urate . METHODS Twenty-three cases with gout receiving furosemide and allopurinol were recruited . Twenty-three controls with gout receiving allopurinol but no diuretics were matched on age , gender , estimated glomerular filtration rate and allopurinol dose . SU , plasma oxypurinol and urinary urate were assessed on a single occasion . The effects of a single dose of furosemide 40 mg were examined in a separate group of 10 patients receiving allopurinol but not diuretic . RESULTS Cases had significantly higher SU and plasma oxypurinol compared with controls despite receiving similar doses of allopurinol . There was no difference in urinary urate excretion . There was a significant increase in area under the curve (AUC)(0 - 24 ) for oxypurinol after administration of furosemide 40 mg . CONCLUSION The interaction between allopurinol and furosemide results in increased SU and plasma oxypurinol . The exact mechanisms remain unclear but complex interactions that result in attenuation of the hypouricaemic effects of oxypurinol are likely . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au , 12609000529246 Background Patients with peripheral arterial disease ( PAD ) are limited by intermittent claudication in the distance they can walk . Allopurinol has been shown in coronary arterial disease to prolong exercise before angina occurs , likely by prevention of oxygen wastage in tissues and reduction of harmful oxidative stress . Methods In this study we evaluated whether allopurinol could prolong the time to development of leg pain in participants with PAD . In a double-blind , r and omized controlled clinical trial participants were r and omized to receive either allopurinol 300 mg twice daily or placebo for 6 months . The primary outcome was change in exercise capacity on treadmill testing at 6 months . Secondary outcomes were 6-minute walking distance , Walking Impairment Question naire , SF-36 question naire , flow-mediated dilatation , and oxidized low-density lipoprotein . Outcome measures were repeated mid study and at the end of study . The mean age of the 50 participants was 68.4 ± 1.2 years with 39 of 50 ( 78 % ) male . Results Five participants withdrew during the study ( 2 active , 3 placebo ) . There was a significant reduction in uric acid levels in those who received active treatment of 52.1 % ( P < 0.001 ) , but no significant change in either the pain-free or the maximum walking distance . Other measures of exercise capacity , blood vessel function , and the participants ' own assessment of their health and walking ability also did not change during the course of the study . Conclusions Although allopurinol has been shown to be of benefit in a number of other diseases , in this study there was no evidence of any improvement after treatment in patients with PAD BACKGROUND Hyperuricemia is a putative risk factor for the progression of chronic kidney disease ( CKD ) . We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD . STUDY DESIGN This was a single-center , double-blind , r and omized , parallel-group , placebo-controlled study . SETTING & PARTICIPANTS Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4 , with asymptomatic hyperuricemia . INTERVENTION The intervention group received febuxostat , 40 mg , once daily for 6 months , while the placebo group received placebo ; both groups were followed up for 6 months . OUTCOMES The primary outcome was the proportion of patients showing a > 10 % decline in estimated glomerular filtration rate ( eGFR ) from baseline in the febuxostat and placebo groups . Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period . RESULTS 45 patients in the febuxostat group and 48 in the placebo group were analyzed . Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 ( SD ) to 34.7±18.1mL/min/1.73m(2 ) at 6 months . With placebo , mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2 ) ( P=0.003 ) . The difference between groups was 6.5 ( 95 % CI , 0.08 - 12.81 ) mL/min/1.73m(2 ) at 6 months ( P=0.05 ) . 17 of 45 ( 38 % ) participants in the febuxostat group had a > 10 % decline in eGFR over baseline compared with 26 of 48 ( 54 % ) from the placebo group ( P<0.004 ) . LIMITATIONS Limitations of this study included small numbers of patients and short follow-up , and ∼10 % of the r and omly assigned population dropped out prior to completion . CONCLUSIONS Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo INTRODUCTION The exact mechanism of chronic nonbacterial prostatitis has not been yet eluci date d and the outcome with the current management is dismal . In this trial , we studied the effect of allopurinol in the treatment of this disease . MATERIAL S AND METHODS In this r and omized double blind controlled trial , a calculated sample size of 56 were grouped into " intervention group " who received allopurinol ( 100 mg tds for 3 months ) with ofloxacin ( 200 mg tds ) for 3 weeks ( n = 29 ) and " control group " who received placebo tablets with ofloxacin ( n = 27 ) . Patients ' scores based on the National Institute of Health Chronic Prostatitis Symptom Score were recorded before therapy and then every month during the study . A four-glass study was performed before intervention and after 3 months . RESULTS The 2 groups were similar regarding outcome variables . In the first month of study , a significant but similar improvement in symptom scores was observed in both groups . Microscopic examination of prostate massage and post-massage sample s were also similar in both groups . No side effects due to allopurinol were observed in patients . CONCLUSION We did not find any advantage for allopurinol in the management of chronic prostatitis versus placebo in patients receiving routine antibacterial treatment BACKGROUND Hyperuricemia is associated with reduced survival among patients with heart failure ( HF ) , but the effect of gout on HF outcomes is unknown . A recent r and omized trial suggested that allopurinol may reduce adverse outcomes among patients with hyperuricemia and HF . Our objective was to determine whether gout and allopurinol use are associated with HF outcomes . METHODS Time-matched , nested case-control analysis of a retrospective cohort of patients with HF who were 66 years or older using health care data bases in Quebec , Canada . The primary outcome measure was a composite measure of HF readmission and all-cause mortality . The secondary outcome measure was all-cause mortality . Rate ratios were calculated using conditional logistic regression and adjusted for known prognostic factors . RESULTS Of the 25,090 patients in this cohort , 14,327 experienced the primary outcome . Both a remote history of gout and an acute episode of gout ( within 60 days of the event date ) were associated with an increased risk of HF readmission or death ( adjusted rate ratio , 1.63 ; 95 % confidence interval , 1.48 - 1.80 ; P<.001 and 2.06 ; 1.39 - 3.06 ; P<.001 , respectively ) . Continuous allopurinol use ( > 30 days of continuous use ) was not associated with the primary outcome among the overall population with HF ( adjusted rate ratio , 1.02 ; 95 % confidence interval , 0.95 - 1.10 ; P=.55 ) but was associated with reduced HF readmissions or death ( 0.69 ; 0.60 - 0.79 ; P<.001 ) and all-cause mortality ( 0.74 ; 0.61 - 0.90 ; P<.001 ) among patients with a history of gout . CONCLUSIONS Patients with HF and a history of gout represent a high-risk population . Among such patients , the use of allopurinol is associated with improved outcomes OBJECTIVES This study sought to ascertain if high-dose allopurinol regresses left ventricular mass ( LVM ) in patients with ischemic heart disease ( IHD ) . BACKGROUND LV hypertrophy ( LVH ) is common in patients with IHD including normotensive patients . Allopurinol , a xanthine oxidase inhibitor , has been shown to reduce LV afterload in IHD and may therefore also regress LVH . METHODS A r and omized , double-blind , placebo-controlled , parallel group study was conducted in 66 patients with IHD and LVH , comparing 600 mg/day allopurinol versus placebo therapy for 9 months . The primary outcome measure was change in LVM , assessed by cardiac magnetic resonance imaging ( CMR ) . Secondary outcome measures were changes in LV volumes by CMR , changes in endothelial function by flow-mediated dilation ( FMD ) , and arterial stiffness by applanation tonometry . RESULTS Compared to placebo , allopurinol significantly reduced LVM ( allopurinol -5.2 ± 5.8 g vs. placebo -1.3 ± 4.48 g ; p = 0.007 ) and LVM index ( LVMI ) ( allopurinol -2.2 ± 2.78 g/m(2 ) vs. placebo -0.53 ± 2.5 g/m(2 ) ; p = 0.023 ) . The absolute mean difference between groups for change in LVM and LVMI was -3.89 g ( 95 % confidence interval : -1.1 to -6.7 ) and -1.67 g/m(2 ) ( 95 % confidence interval : -0.23 to -3.1 ) , respectively . Allopurinol also reduced LV end-systolic volume ( allopurinol -2.81 ± 7.8 mls vs. placebo + 1.3 ± 7.22 mls ; p = 0.047 ) , improved FMD ( allopurinol + 0.82 ± 1.8 % vs. placebo -0.69 ± 2.8 % ; p = 0.017 ) and augmentation index ( allopurinol -2.8 ± 5.1 % vs. placebo + 0.9 ± 7 % ; p = 0.02 ) . CONCLUSIONS High-dose allopurinol regresses LVH , reduces LV end-systolic volume , and improves endothelial function in patients with IHD and LVH . This raises the possibility that allopurinol might reduce future cardiovascular events and mortality in these patients . ( Does a Drug Allopurinol Reduce Heart Muscle Mass and Improve Blood Vessel Function in Patients With Normal Blood Pressure and Stable Angina ? ; IS RCT N73579730 ) OBJECTIVE Free radicals produced by the hypoxanthine-xanthine oxidase reaction in ischemia/reperfusion experiments have been proposed as contributing to myocardial cell necrosis in acute myocardial infa rct ion . In this study , the hypothesis was tested that a commonly observed late phase of necrosis , infa rct extension , could be prevented by allopurinol , an inhibitor of xanthine oxidase . STUDY DESIGN Allopurinol , a xanthine oxidase inhibitor , was used with placebo in a double-blind r and omized therapy study in 140 patients with ischemic heart disease admitted to the authors ' hospital . Eighty-four had acute myocardial infa rct ion and the remaining 56 had unstable angina . Of the 84 patients with infa rct ion , 39 received allopurinol treatment . If xanthine oxidase production of cytotoxic free radical plays a major role in the pathogenesis of infa rct extension , blockade of the reaction with allopurinol should decrease the occurrence of extension . RESULTS Nineteen infa rct extensions were observed ; five ( 11 % ) in the placebo group and 14 ( 36 % ) in the allopurinol . CONCLUSIONS The increased incidence of extension ( P less than 0.007 ) in the treatment group does not support the hypothesis that xanthine oxidase contributes to infa rct extension , which is consistent with recent reports that xanthine oxidase is not a significant component of the human myocardium . These findings indicate that allopurinol may actually be contraindicated in patients with ischemic heart disease OBJECTIVES This study sought to ascertain whether high-dose allopurinol causes regression of left ventricular mass ( LVM ) in patients with type 2 diabetes mellitus ( T2DM ) . BACKGROUND Left ventricular hypertrophy ( LVH ) is common in T2DM and contributes to patients ' high cardiovascular ( CV ) event rate . Oxidative stress ( OS ) has been implicated in LVH development , and allopurinol has been previously shown to reduce vascular OS . We therefore investigated whether allopurinol causes regression of LVH in patients with T2DM . METHODS We conducted a r and omized , double-blind , placebo-controlled study of 66 optimally-treated T2DM patients with echocardiographic evidence of LVH . Allopurinol , 600 mg/day , or placebo was given over the study period of 9 months . The primary outcome was reduction in LVM as calculated by cardiac magnetic resonance imaging at baseline and at 9 months ' follow-up . Secondary endpoints were change in flow-mediated dilation and augmentation index . RESULTS Allopurinol significantly reduced absolute LVM ( -2.65 ± 5.91 g vs. placebo group + 1.21 ± 5.10 g [ p = 0.012 ] ) and LVM indexed to body surface area ( -1.32 ± 2.84 g/m(2 ) vs. placebo group + 0.65 ± 3.07 g/m(2 ) [ p = 0.017 ] ) . No significant changes were seen in either flow-mediated dilation or augmentation index . CONCLUSIONS Allopurinol causes regression of LVM in patients with T2DM and LVH . Regression of LVH has been shown previously to improve CV mortality and morbidity . Therefore , allopurinol therapy may become useful to reduce CV events in T2DM patients with LVH . ( Allopurinol in Patients with Diabetes and LVH ; UKCRN 8766 ) OBJECTIVE Gout affects approximately 1 - 2 % of the American population . Current options for treating hyperuricemia in chronic gout are limited . The purpose of this study was to assess the safety and efficacy of febuxostat , a nonpurine selective inhibitor of xanthine oxidase , in establishing normal serum urate ( sUA ) concentrations in gout patients with hyperuricemia ( > or=8.0 mg/dl ) . METHODS We conducted a phase II , r and omized , double-blind , placebo-controlled trial in 153 patients ( ages 23 - 80 years ) . Subjects received febuxostat ( 40 mg , 80 mg , 120 mg ) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after r and omization . The primary end point was the proportion of subjects with sUA levels < 6.0 mg/dl on day 28 . RESULTS Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level < 6.0 mg/dl at each visit ( P < 0.001 for each comparison ) . The targeted sUA level was attained on day 28 in 0 % of those taking placebo and in 56 % of those taking 40 mg , 76 % taking 80 mg , and 94 % taking 120 mg of febuxostat . The mean sUA reduction from baseline to day 28 was 2 % in the placebo group and 37 % in the 40-mg , 44 % in the 80-mg , and 59 % in the 120-mg febuxostat groups . Gout flares occurred with similar frequency in the placebo ( 37 % ) and 40-mg febuxostat ( 35 % ) groups and with increased frequency in the higher dosage febuxostat groups ( 43 % taking 80 mg ; 55 % taking 120 mg ) . During colchicine prophylaxis , gout flares occurred less frequently ( 8 - 13 % ) . Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups . CONCLUSION Treatment with febuxostat result ed in a significant reduction of sUA levels at all dosages . Febuxostat therapy was safe and well tolerated Acute experiments of uric acid infusion in animals and the clinical observation that in patients with gout there is an increased incidence of renal lesions , suggested that high levels of plasma uric acid may be detrimental to the kidney and cause a decrease in renal function . It is not known , however , whether hyperuricemia , not clinical ly associated with gout , causes kidney damage , nor is it known whether therapeutic reduction of serum uric acid levels slows the rate of the deterioration of renal function in such patients . To establish whether maintenance of normal plasma uric acid concentration in patients with hyperuricemia associated with various diseases has any effect on serial determination of GFR or slows the rate of kidney deterioration , this study was planned OBJECTIVE An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders . Adenosine agonists have been shown to have properties similar to those of dopamine antagonists ; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum , and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors . Allopurinol increases adenosine levels in the brain , and hence is hypothesized to reduce the symptoms of mania . Two r and omized , placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale ( YMRS ) scores for drug compared to placebo , while a more recent , relatively small , add-on study showed negative results . Based on these data , our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and /or antipsychotic agents in manic patients with bipolar disorder . METHODS We performed a large , well-powered , multicenter , six-week , r and omized , placebo-controlled trial of allopurinol added to mood stabilizers and /or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode . RESULTS Both groups showed improvement on the YMRS ( effect size of 1.5 for placebo and 1.6 for allopurinol ) , with no difference observed between groups on YMRS scores ( t = 0.28 , p = 0.78 ) . There was no difference in the proportion of patients who responded to treatment ( defined as showing at least 50 % improvement in YMRS score ) between the two groups ( p = 0.92 ) , or in dropout rates ( p = 0.84 ) . LIMITATIONS None of our patients received lithium . However , the side effects of lithium and its narrow therapeutic index made the use of lithium less common and , therefore , our study results reflect common current clinical practice . In the present study , we used a variety of antipsychotic and /or mood stabilizing treatments , to which we added allopurinol ; one might hypothesize that add-on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers . CONCLUSIONS The findings of this large , well-powered study do not support add-on allopurinol as a treatment for acute mania . This study did not test the efficacy of allopurinol as monotherapy BACKGROUND Adenosine has been proposed to be an endogenous anticonvulsant agent . It inhibits glutamate release from excitatory neurons and neuronal firing . Therefore , adenosine agonists have potential clinical application as antiepileptics . In this double-blind r and omized , placebo-controlled trial , we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy . METHODS Thirty eight patients were r and omly allocated equally to allopurinol+preexisting antiepileptic ( Group A ) or placebo+preexisting antiepileptic ( Group B ) for a 6-month , double-blind , placebo-controlled study . The dose of allopurinol was titrated up to 300 mg/day ( 100 mg TDS ) . The dose of preexisting medications was maintained without change over the trial . The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks . RESULTS Of 38 participants , 32 patients completed the study . There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial . Seizures reduction of > 30 % in 66 % , > 50 % in 55 % , and > 60 % in 44 % of cases in the allopurinol group was achieved after 2 months and persisted during the study . Nevertheless , only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration . In the allopurinol group , two patients had transient rashes , two patients had mild nausea , and two experienced dizziness , but only one patient discontinued the drug due to dizziness . In the placebo group , one patient had rash and one patient had nausea . In addition , no significant hematological or hepatic changes were found during the trial in both groups . CONCLUSIONS The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy . Based on this study , we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy The importance of xanthine oxidase and its products is being increasingly recognized in cardiovascular medicine . Patients who have had a stroke are at high risk of future cardiovascular events and this risk is higher in those with high urate levels . The aim of this pilot study was to see if inhibiting xanthine oxidase altered arterial wave reflection , determined from the augmentation index ( AIx ) . In a double-blind study , 30 patients with high urate ( > or = 0.38 mmol/L ) were r and omized to 300 mg allopurinol or placebo for 8 weeks . AIx measurements were made before and after treatment using the vali date d SphygmoCor pulse waveform analysis system . For patients treated with allopurinol , there was a reduction in AIx from 26.08 + /- 3.31 % to 20.15 + /- 2.23 % compared with an increase in the placebo group from 23.57 + /- 3.13 % to 27.64 + /- 3.44 % ( P = 0.031 , ANOVA ) . The vascular benefits of allopurinol are rapidly emerging . We have demonstrated that allopurinol has beneficial effects on AIx , a vali date d measure of vascular function . A further larger study is warranted to look at whether a therapeutic intervention with allopurinol will impact positively on mortality and morbidity in stroke survivors Background and Objective There is growing evidence of an association between high uric acid ( UA ) levels and cardiovascular disease ( CVD ) . We hypothesized that febuxostat , a xanthine oxidase inhibitor , may be associated with suppressing the renin-angiotensin-aldosterone system ( RAAS ) and improving renal function in hyperurecemic patients with hypertension . Methods We conducted a 6-month prospect i ve study in which we r and omized hypertensive hyperuricemic patients to either a febuxostat group ( n = 30 ) or a control group ( n = 30 ) . The dose of febuxostat was adjusted to maintain the serum UA level at < 6.0 mg/dL. Results In the febuxostat group , the plasma renin activity ( PRA ) , plasma aldosterone concentration ( PAC ) , and serum UA level significantly decreased by 33 % ( p = 0.0012 ) , 14 % ( p = 0.001 ) , and 29 % ( p < 0.0001 ) , respectively . The estimated glomerular filtration rate ( eGFR ) significantly increased by 5.5 % ( p = 0.001 ) . Similar changes were not observed in the control group . Furthermore , a significant correlation was observed between the percent changes in the serum UA levels and the percent changes in the PRA ( r = 0.277 , p = 0.033 ) , PAC ( r = 0.310 , p = 0.016 ) , serum blood urea nitrogen levels ( r = 0.434 , p = 0.0005 ) , serum creatinine levels ( r = 0.413 , p = 0.002 ) , and eGFR ( r = −0.474 , p = 0.0001 ) . Conclusions These results support the hypothesis that febuxostat might not only reduce serum UA levels but also suppress RAAS and improve renal function in hyperuricemic patients with hypertension , possibly leading to prevention of CVD To investigate the value of combined treatment with allopurinol and 5‐aminosalicylic ( 5‐ASA ) based drugs as maintenance treatment for ulcerative colitis ( UC ) BACKGROUND AND OBJECTIVES Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation . Febuxostat , a xanthine oxidoreductase inhibitor , is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout . This work studied whether febuxostat , compared with allopurinol and placebo , would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this 6-month , double-blind , multicenter , r and omized controlled trial , hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm ( as seen by multidetector computed tomography ) received daily febuxostat at 80 mg , allopurinol at 300 mg , or placebo . The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid . Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance . RESULTS Of 99 enrolled participants , 86 participants completed the study . Febuxostat led to significantly greater reduction in 24-hour urinary uric acid ( -58.6 % ) than either allopurinol ( -36.4 % ; P=0.003 ) or placebo ( -12.7 % ; P<0.001 ) . Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo . There was no change in stone size , stone number , or renal function . No new safety concerns were noted for either drug . CONCLUSIONS Febuxostat ( 80 mg ) lowered 24-hour urinary uric acid significantly more than allopurinol ( 300 mg ) in stone formers with higher urinary uric acid excretion after 6 months of treatment . There was no change in stone size or number over the 6-month period OBJECTIVE This study sought to observe the effects of allopurinol on the cardiac function of non-hyperuricaemic patients with chronic heart failure and determine the safety of allopurinol for clinical applications . PATIENTS AND METHODS A group of 125 consecutive cases of non-hyperuricaemic patients with chronic heart failure who were treated at Chongqing Emergency Medical Centre between July 2011 and June 2012 were enrolled and were r and omly divided into allopurinol ( 300 mg/day ) group ( n=62 ) and control group ( n=63 ) . During the six months treatment period , levels of cardiac function , brachial artery endothelial function , inflammatory cytokines , and biochemical markers were routinely examined . RESULTS After three months of allopurinol treatment , patients exhibited an increase in flow-mediated vasodilatation ( FMD ) of brachial artery , whereas , after six months of treatment , the cardiac function classification was improved ; plasma levels of brain natriuretic peptide and tumour necrosis factor-a were decreased ; left ventricular internal diameter was diminished ; and the ejection fraction was increased ( p<0.01 for all the parameters ) in patients . Serum uric acid level was decreased during the treatment period for both groups , with no significant difference between the two groups . Liver and kidney dysfunction was not observed among the study participants , and no significant increase in creatine kinase level was detected for either treatment group . CONCLUSIONS For non-hyperuricaemic patients with chronic heart failure , the addition of six months of allopurinol therapy was safe and effective . Moreover , in these patients , allopurinol treatment not only can significantly ameliorate the left ventricular function and reduce the level of inflammatory factors but could also improve endothelial function OBJECTIVE To compare the urate-lowering efficacy and safety of febuxostat , allopurinol , and placebo in a large group of subjects with hyperuricemia and gout , including persons with impaired renal function . METHODS Subjects ( n = 1,072 ) with hyperuricemia ( serum urate level > or = 8.0 mg/dl ) and gout with normal or impaired ( serum creatinine level > 1.5 to < or = 2.0 mg/dl ) renal function were r and omized to receive once-daily febuxostat ( 80 mg , 120 mg , or 240 mg ) , allopurinol ( 300 or 100 mg , based on renal function ) , or placebo for 28 weeks . RESULTS Significantly ( P < or = 0.05 ) higher percentages of subjects treated with febuxostat 80 mg ( 48 % ) , 120 mg ( 65 % ) , and 240 mg ( 69 % ) attained the primary end point of last 3 monthly serum urate levels < 6.0 mg/dl compared with allopurinol ( 22 % ) and placebo ( 0 % ) . A significantly ( P < 0.05 ) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg ( 4 [ 44 % ] of 9 ) , 120 mg ( 5 [ 45 % ] of 11 ) , and 240 mg ( 3 [ 60 % ] of 5 ) achieved the primary end point compared with those treated with 100 mg of allopurinol ( 0 [ 0 % ] of 10 ) . Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups , although diarrhea and dizziness were more frequent in the febuxostat 240 mg group . The primary reasons for withdrawal were similar across groups except for gout flares , which were more frequent with febuxostat than with allopurinol . CONCLUSION At all doses studied , febuxostat more effectively lowered and maintained serum urate levels < 6.0 mg/dl than did allopurinol ( 300 or 100 mg ) or placebo in subjects with hyperuricemia and gout , including those with mild to moderately impaired renal function Abstract : Allopurinol may have protective effects over ischemic reperfusion injury and reduce infa rct size . In this r and omized study , we aim ed to evaluate the impact of allopurinol in patients with acute ST elevation myocardial infa rct ion ( STEMI ) undergoing thrombolytic therapy . Overall , 140 patients with STEMI were r and omly assigned to receive 400 mg of allopurinol or placebo before treating with streptokinase . Then , study group received 100 mg of allopurinol daily for 28 days and placebo group received placebo for the same period . ST resolution rate in 90 minutes , in-hospital mortality , and major adverse cardiac events ( MACE ) were compared . Compared to placebo group , patients receiving allopurinol had significantly higher rate of ST resolution rate ≥50 % ( 68.8 % vs. 50 % , P = 0.04 ) and lower levels of peak Creatine kinase ( CK ) ( P = 0.003 ) , Creatine Kinase-MB ( CK-MB ) ( P = 0.005 ) , and Cardiac Troponin I ( CTnI ) ( P < 0.001 ) . Also , patients in allopurinol group had significantly lower rate of in-hospital MACE ( P = 0.03 ) , but there was no significant difference between groups regarding in-hospital mortality and cardiac events . In patients admitted with STEMI who are c and i date s of thrombolytic therapy , allopurinol is associated with better 90-minute ST resolution , lower enzymatically determined infa rct size , and in-hospital MACE . More powerful studies are needed to determine the effect on mortality AIMS New preventative strategies for stroke are required . One promising strategy is uric acid reduction and xanthine oxidase inhibition with allopurinol . We sought to investigate whether allopurinol improves cerebrovascular reactivity ( CVR ) following subcortical stroke . METHODS We performed a r and omized , double-blind , controlled study to investigate the effect of a 3-month course of 300 mg allopurinol once daily vs. placebo on CVR in individuals with recent ( within 6 months ) subcortical stroke . Participants were r and omized on a 1:1 basis . CVR was defined as the percentage change in middle cerebral artery flow velocity following an intravenous injection of 15 mg kg(-1 ) of acetazolamide . Our primary end-point was the CVR difference between baseline and 3 months . Secondary end-points included measures of peripheral vascular reactivity and blood markers of inflammation and endothelial activation . RESULTS We enrolled 50 participants ; 45 completed the protocol . Baseline serum urate was 0.35 mmol l(-1 ) ( SD 0.1 ) and 0.34 mmol l(-1 ) ( SD 0.1 ) in the allopurinol and placebo groups , respectively . There were no serious adverse events related to treatment . CVR did not change following treatment with allopurinol [ median CVR change 0.89 % after allopurinol ( n = 20 ) and -0.68 % after placebo ( n = 25 ) ; 95 % confidence interval for estimated difference in medians -13.4 , 25.5 , P = 0.64 ] . Urate was significantly lowered by allopurinol but no change in other secondary end-points was seen . CONCLUSION Xanthine oxidase inhibition with allopurinol has previously been shown to improve cerebrovascular function , but no benefit was seen in this study . It may therefore be that previous encouraging findings will not translate into important clinical benefits OBJECTIVES This study evaluated whether a xanthine oxidase ( XO ) inhibitor , oxypurinol , produces clinical benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy . BACKGROUND Increased XO activity may contribute to heart failure pathophysiology . METHODS Patients ( n = 405 ) were r and omized to oxypurinol ( 600 mg/day ) or placebo . Efficacy at 24 weeks was assessed using a composite end point comprising heart failure morbidity , mortality , and quality of life . RESULTS The percentage of patients characterized as improved , unchanged , or worsened did not differ between those receiving oxypurinol or placebo . Oxypurinol reduced serum uric acid ( SUA ) by approximately 2 mg/dl ( p < 0.001 ) . In a subgroup analysis , patients with elevated SUA ( > 9.5 mg/dl , n = 108 ) responded favorably to oxypurinol ( p = 0.02 for interaction term ) , whereas oxypurinol patients with SUA < 9.5 mg/dl exhibited a trend towards worsening . In addition , SUA reduction to oxypurinol correlated with favorable clinical response . Within the entire oxypurinol patient cohort , those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who worsened ( -2.3 + /- 2.1 mg/dl vs. -1.0 + /- 1.9 mg/dl , p = 0.0006 ) . In placebo patients , lower baseline SUA , but not change in SUA , correlated with improved clinical outcome . CONCLUSIONS Oxypurinol did not produce clinical improvements in unselected patients with moderate-to-severe heart failure . However , post-hoc analysis suggests that benefits occur in patients with elevated SUA in a manner correlating with the degree of SUA reduction . Serum uric acid may serve as a valuable biomarker to target XO inhibition in heart failure . ( Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure ; NCT00063687 ) Fructose and sodium intake have been associated with hypertension and metabolic syndrome . Although various mechanisms are involved , fructose causes hypertension partly through rising intracellular and serum uric acid . To date , there are no studies in adults that have evaluated the impact of low fructose diets and allopurinol on prehypertensive and overweight subjects . The objective of this study was to compare the effect of low fructose diet and allopurinol or placebo on blood pressure ( BP ) and metabolic syndrome components The study was a controlled clinical trial and consisted of two phases ; in the first phase of intervention ( 4 weeks ) , patients were r and omized to either low fructose diet ( 34 patients ) or control diet ( 38 patients ) . In the second phase of intervention ( weeks 4 - 8 ) , the same groups continued with the same diet prescriptions but were further r and omized to receive placebo or allopurinol ( 300 mg/d ) . Clinic and 24-hour ambulatory BP , anthropometric measures , and laboratory data were determined at baseline , weeks 4 and 8 . Seventy-two patients were included in the trial . At the end of the dietary phase , both diet groups significantly reduced their BP , but there were no between-group differences . Compared to placebo , at the end of follow-up , subjects in the allopurinol group had a lower clinic systolic blood pressure and this was significant within- and between-group comparisons . The percentage of dippers was higher in the allopurinol group , and weight was reduced significantly despite the absence of caloric restriction Allopurinol was associated with a significant reduction in clinic BP , an increase in the percentage of dippers , and significant weight loss . Larger studies with longer follow-up are needed to confirm our findings Hyperuricemia may contribute to endothelial dysfunction in CKD . We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia ( ≥7 mg/dl in men and ≥6 mg/dl in women ) r and omized in a double-blinded manner to receive placebo or allopurinol for 12 weeks . R and omization was stratified according to presence or absence of diabetes mellitus . We measured vascular endothelial function by brachial artery flow-mediated dilation . No significant differences existed between groups at baseline ; 61 % of the participants had diabetes mellitus in both groups . The placebo and the allopurinol groups had baseline serum uric acid levels ( SDs ) of 8.7 ( 1.6 ) mg/dl and 8.3 ( 1.4 ) mg/dl , respectively , and baseline flow-mediated dilation values ( SDs ) of 6.0 % ( 5.0 % ) and 4.8 % ( 5.0 % ) , respectively . Compared with placebo , allopurinol lowered serum uric acid significantly but did not improve endothelial function . In participants without diabetes mellitus , allopurinol associated with a trend toward improved flow-mediated dilation ( + 1.4 % [ 3.9 % ] versus -0.7 % [ 4.1 % ] with placebo ) , but this was not statistically significant ( P=0.26 ) . Furthermore , we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress . In conclusion , allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients Abstract Objectives . Endothelial dysfunction is a well known risk factor for atherosclerosis . Uric acid levels are associated with endothelial dysfunction and atherosclerosis even if in physiological range . Xanthine oxidase inhibition with allopurinol decreases uric acid levels and oxidative stress and improves endothelial function . We have investigated the effect of high-dose and long-term allopurinol therapy on endothelial function in diabetic normotensive patients . Methods . This study is a r and omized , single-blind , placebo-controlled trial . Both treatment and placebo groups consisted of 50 patients . In the treatment group , daily oral 900 mg allopurinol was started after r and omization and maintained for 12 weeks . Brachial artery flow-mediated dilatation ( FMD ) and nitrate-induced dilatation ( NID ) were measured at baseline and after the allopurinol therapy to evaluate endothelial function . Results . HbA1c and uric acid levels decreased after allopurinol therapy ( 6.1 ± 2.1 vs 5.5 ± 1.0 % , 5.0 ± 0.8 vs 3.3 ± 0.5 mg/dl , respectively , p = 0.01 ) but no change was observed in the placebo group ( 7.7 ± 1.9 % vs 7.6 ± 2.0 % , 5.3±2.1 vs 5.6 ± 0.8 mg/dl , respectively , p > 0.05 ) . FMD and NID increased significantly in the treatment group ( 5.6 ± 2.1 % vs 8.5 ± 1.2 % , 10 ± 7.4 % vs 14 ± 4.0 % , 10 ± 7.4 % vs 14 ± 4.0 % , respectively , p = 0.01 ) , whereas no change was observed in the placebo group ( 5.8 ± 1.8 % vs 6.1 ± 0.8 % , 12 ± 9.5 vs 10 ± 3.8 % , respectively , p > 0.05 ) . Conclusion . Long-term and high-dose allopurinol therapy significantly improved endothelial function in diabetic normotensive patients . In addition , allopurinol therapy contributes to the lower HbA1c levels |
11,202 | 27,507,055 | Hemorrhagic events associated with ramucirumab are modest and manageable while patients could continue to receive ramucizumab treatment to achieve their maximum clinical benefits | The purpose of this study was to investigate the overall incidence and relative risk ( RR ) of hemorrhagic events in cancer patients treated with ramucirumab . | BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline ) were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company OBJECTIVE Vascular endothelial growth factor ( VEGF ) receptor-mediated signaling contributes to ovarian cancer pathogenesis . Elevated VEGF expression is associated with poor clinical outcomes . We investigated ramucirumab , a fully human anti-VEGFR-2 antibody , in patients with persistent or recurrent epithelial ovarian , fallopian tube , or primary peritoneal carcinoma . Primary endpoints were progression-free survival at 6 months ( PFS-6 ) and confirmed objective response rate ( ORR ) . METHODS Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of < 12 months with measurable disease were eligible . Patients received 8 mg/kg ramucirumab intravenously every 2 weeks . RESULTS Sixty patients were treated ; one patient remained on study as of September 2013 . The median age was 62 years ( range : 27 - 80 ) , and median number of prior regimens was 3 . Forty-five ( 75 % ) patients had platinum refractory/resistant disease . Thirty-nine patients ( 65.0 % ) had serous tumors . PFS-6 was 25.0 % ( n=15/60 , 95 % CI : 14.7 - 37.9 % ) . Best overall response was : partial response 5.0 % ( n=3/60 ) , stable disease 56.7 % ( n=34/60 ) , and progressive disease 33.3 % ( n=20/60 ) . The most common treatment-emergent adverse events possibly related to study drug were headache ( 65.0 % ; 10.0 % Grade ≥ 3 ) , fatigue ( 56.7 % ; 3.3 % Grade ≥ 3 ) , diarrhea ( 28.3 % ; 1.7 % Grade ≥ 3 ) , hypertension ( 25.0 % ; 3.3 % Grade ≥ 3 ) , and nausea ( 20.0 % ; no Grade ≥ 3 ) . Two patients experienced intestinal perforations ( 3.3 % Grade ≥ 3 ) . Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion , including increased VEGF-A , PlGF and decreased sVEGFR-2 . CONCLUSIONS Although antitumor activity was observed , the predetermined efficacy endpoints were not met BACKGROUND Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 . We aim ed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy . METHODS In this multicentre , double-blind , r and omised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen . Patients were r and omly allocated ( 1:1 ) with a central ised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m(2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death . The primary endpoint was overall survival in all patients allocated to treatment . We assessed adverse events according to treatment received . This study is registered with Clinical Trials.gov , number NCT01168973 . FINDINGS Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were r and omly allocated to treatment . Median overall survival was 10·5 months ( IQR 5·1 - 21·2 ) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months ( 4·2 - 18·0 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 0·86 , 95 % CI 0·75 - 0·98 ; p=0·023 ) . Median progression-free survival was 4·5 months ( IQR 2·3 - 8·3 ) for the ramucirumab group compared with 3·0 months ( 1·4 - 6·9 ) for the control group ( 0·76 , 0·68 - 0·86 ; p<0·0001 ) . We noted treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population . The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ramucirumab group vs 246 [ 40 % ] in the control group ) , febrile neutropenia ( 100 [ 16 % ] vs 62 [ 10 % ] ) , fatigue ( 88 [ 14 % ] vs 65 [ 10 % ] ) , leucopenia ( 86 [ 14 % ] vs 77 [ 12 % ] ) , and hypertension ( 35 [ 6 % ] vs 13 [ 2 % ] ) . The numbers of deaths from adverse events ( 31 [ 5 % ] vs 35 [ 6 % ] ) and grade 3 or worse pulmonary haemorrhage ( eight [ 1 % ] vs eight [ 1 % ] ) did not differ between groups . Toxicities were manageable with appropriate dose reductions and supportive care . INTERPRETATION Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC . FUNDING Eli Lilly Purpose : To assess the efficacy and safety of the anti-VEGF receptor-2 ( VEGFR-2 ) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers . Experimental Design : Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity . The primary endpoint was progression-free survival ( PFS ) ; secondary endpoints included objective response rate ( ORR ) and overall survival ( OS ) . Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients . Results : Forty-two patients received ramucirumab . Median PFS was 4.0 months [ 95 % confidence interval ( CI ) , 2.6–5.7 ] , ORR was 9.5 % ( 95 % CI , 2.7–22.6 ; 4/42 patients had a partial response ) , and median OS was 12.0 months ( 95 % CI , 6.1–19.7 ) . For patients with Barcelona Clinic Liver Cancer ( BCLC ) stage C disease , median OS was 4.4 months ( 95 % CI , 0.5–9.0 ) for patients with Child-Pugh B cirrhosis versus 18.0 months ( 95 % CI , 6.1–23.5 ) for patients with Child-Pugh A cirrhosis . Treatment-related grade ≥3 toxicities included hypertension ( 14 % ) , gastrointestinal hemorrhage and infusion-related reactions ( 7 % each ) , and fatigue ( 5 % ) . There was one treatment-related death ( gastrointestinal hemorrhage ) . After treatment with ramucirumab , there was an increase in serum VEGF and placental growth factor ( PlGF ) and a transient decrease in soluble VEGFR-2 . Conclusion : Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile . Exploratory biomarker studies showed changes in circulating VEGF , PlGF , and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents . Clin Cancer Res ; 19(23 ) ; 6614–23 . © 2013 AACR BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems PURPOSE To evaluate the safety , maximum-tolerated dose ( MTD ) , pharmacokinetics ( PKs ) , pharmacodynamics , and preliminary anticancer activity of ramucirumab ( IMC-1121B ) , a fully human immunoglobulin G(1 ) monoclonal antibody targeting the vascular endothelial growth factor receptor (VEGFR)-2 . PATIENTS AND METHODS Patients with advanced solid malignancies were treated once weekly with escalating doses of ramucirumab . Blood was sample d for PK studies throughout treatment . The effects of ramucirumab on circulating vascular endothelial growth factor-A ( VEGF-A ) , soluble VEGFR-1 and VEGFR-2 , tumor perfusion , and vascularity using dynamic contrast-enhanced magnetic resonance imaging were assessed . Results Thirty-seven patients were treated with 2 to 16 mg/kg of ramucirumab . After one patient each developed dose-limiting hypertension and deep venous thrombosis at 16 mg/kg , the next lower dose ( 13 mg/kg ) was considered the MTD . Nausea , vomiting , headache , fatigue , and proteinuria were also noted . Four ( 15 % ) of 27 patients with measurable disease had a partial response ( PR ) , and 11 ( 30 % ) of 37 patients had either a PR or stable disease lasting at least 6 months . PKs were characterized by dose-dependent elimination and nonlinear exposure consistent with saturable clearance . Mean trough concentrations exceeded biologically relevant target levels throughout treatment at all dose levels . Serum VEGF-A increased 1.5 to 3.5 times above pretreatment values and remained in this range throughout treatment at all dose levels . Tumor perfusion and vascularity decreased in 69 % of evaluable patients . CONCLUSION Objective antitumor activity and antiangiogenic effects were observed over a wide range of dose levels , suggesting that ramucirumab may have a favorable therapeutic index in treating malignancies amenable to VEGFR-2 inhibition |
11,203 | 29,566,078 | Adding concurrent chemotherapy to IMRT led to no survival benefit and increased acute toxicity reactions for stage II nasopharyngeal carcinoma | OBJECTIVES To compare clinical outcomes of concurrent chemoradiotherapy ( CCRT ) with those of radiotherapy alone for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy ( IMRT ) era . | BACKGROUND Concurrent chemoradiotherapy ( CCRT ) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma ( NPC ) patients compared with radiotherapy ( RT ) alone , but the effectiveness of the combined therapy for stage II NPC patients is unknown . METHODS Patients with Chinese 1992 stage II NPC were r and omly assigned to receive either RT alone ( n = 114 ) or CCRT ( n = 116 ) . The CCRT patients were given concurrent cisplatin ( 30 mg/m(2 ) on day 1 ) weekly during RT . The primary endpoint was overall survival ( OS ) . Secondary endpoints were progression-free survival ( PFS ) , distant metastasis-free survival , and locoregional relapse-free survival . All patients were analyzed by the intent-to-treat principle . The Cox proportional hazards model was used to calculate hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) and in multivariable analyses to test the independent statistical significance of treatment intervention . Toxic effects and the response to treatment were analyzed using the χ(2 ) test . All statistical tests were two-sided . RESULTS With a median follow-up of 60 months , adding chemotherapy statistically significantly improved the 5-year OS rate ( 94.5 % vs 85.8 % ; HR of death = 0.30 , 95 % CI = 0.12 to 0.76 ; P = .007 ) , PFS ( 87.9 % vs 77.8 % ; HR of progression = 0.45 , 95 % CI = 0.23 to 0.88 ; P = .017 ) , and distant metastasis-free survival ( 94.8 % vs 83.9 % ; HR of distant relapse = 0.27 , 95 % CI = 0.10 to 0.74 ; P = .007 ) ; however , there was no statistically significant difference in the 5-year locoregional relapse-free survival rate ( 93.0 % vs 91.1 % ; HR of locoregional relapse = 0.61 , 95 % CI = 0.25 to 1.51 ; P = .29 ) . Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS , PFS , and distant control in stage II NPC . The CCRT arm experienced statistically significantly more acute toxic effects ( P = .001 ) , although the rate of late toxic effects did not increase statistically significantly . CONCLUSION Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC Objectives : To evaluate the treatment outcome of patients with stage IIB nasopharyngeal carcinoma ( NPC ) after definitive intensity-modulated radiotherapy ( IMRT ) without concurrent chemotherapy . Methods : Between August 2003 and December 2006 , 107 patients with T1N1M0 ( 8 % ) , T2N0M0 ( 13 % ) , or T2N1M0 ( 79 % ) NPC were definitively treated with IMRT . Sixty-one received IMRT only , and 46 patients had various strategies of systemic treatment , consisting of abbreviated neoadjuvant ( 38 patients ) , concurrent ( 8 patients ) , or adjuvant ( 16 patients ) chemotherapy . Radiation doses prescribed to the planning tumor volume of the gross disease , high-risk clinical tumor volume , and low-risk clinical tumor volume were 66 to 70 Gy , 54 to 60 Gy , and 50–54 Gy , respectively . Results : With a median follow-up of 39 months ( range , 7–77 months ) , 6 patients had locoregional relapse : 1 local only , 1 locoregional , and 4 regional only . Five patients had distant failure . Five of 6 total deaths were cancer related . The 3-year estimated local control , regional control , metastasis-free survival , disease-free survival , and overall survival were 96.5 % , 98 % , 94.8 % , 90.7 % , and 95.8 % , respectively . No significant difference in treatment outcome was demonstrated in patients treated with or without chemotherapy of any schedule . Conclusions : IMRT without concurrent chemotherapy provides good outcome for patients with stage IIB NPC with acceptable toxicity . Neoadjuvant chemotherapy did not appear to provide significant additional benefit for this patient subgroup . Further investigation in the prospect i ve setting is warranted to explore the role of systemic agents in the treatment of NPC with limited primary disease and cervical lymphadenopathy when IMRT is used PURPOSE To investigate the feasibility of intensity-modulated radiation therapy ( IMRT ) with or without chemotherapy , and to assess toxicities , failure patterns , and survivals in patients with nasopharyngeal carcinoma ( NPC ) . PATIENTS AND METHODS Radiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any N+ disease and 59.4 Gy given to sub clinical disease , delivered over 33 treatment days . Patients with stage T2b or greater or with N+ disease also received concurrent cisplatin ( 100 mg/m(2 ) ) on days 1 , 22 , and 43 followed by adjuvant cisplatin ( 80 mg/m(2 ) ) on day 1 ; fluorouracil ( 1,000 mg/m(2)/d ) on days 1 through 4 administered every 4 weeks for three cycles . Tumor , clinical status , and acute/late toxicities were assessed . The primary objective was to test the transportability of IMRT to a multi-institutional setting . RESULTS Between February 2003 and November 2005 , 68 patients with stages I through IVB NPC ( of which 93.8 % were WHO types 2 and 3 ) were enrolled . Prescribed IMRT ( target delineation ) was given to 83.8 % , whereas 64.9 % received chemotherapy per protocol . The estimated 2-year local progression-free ( PF ) , regional PF , locoregional PF , and distant metastasis-free rates were 92.6 % , 90.8 % , 89.3 % , and 84.7 % , respectively . The estimated 2-year PF and overall survivals were 72.7 % and 80.2 % , respectively . Acute grade 4 mucositis occurred in 4.4 % , and the worst late grade 3 toxicities were as follows : esophagus , 4.7 % ; mucous membranes , 3.1 % ; and xerostomia , 3.1 % . The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5 % . Only two patients complained of grade 3 xerostomia , and none had grade 4 xerostomia . CONCLUSION It was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90 % LRPF rate reproducing excellent reports from single institutions . Minimal grade 3 and lack of grade 4 xerostomia were encouraging Abstract The objective of this study was to evaluate the necessity of concurrent chemotherapy in T1 - 2N1 nasopharyngeal carcinoma ( NPC ) patients treated with intensity-modulated radiation therapy (IMRT).The retrospective analysis was conducted using the paired comparison method . We matched cases to controls using the greedy matching algorithm with 1:1 control to case ratio . Controls were matched to cases by factors including age , gender , T stage , and duration of RT . The control group included patients received IMRT alone . In another group , concurrent chemotherapy ( DDP 40 mg/m2/w ) was administrated to each paired patient . From Jan 2009 to Dec 2011 , a total of 86 well-balanced T1 - 2N1 ( 2002 UICC staging system ) NPC patients were retrospectively analyzed . Half of them ( 43 patients ) received radical IMRT alone and another 43 received concurrent chemotherapy with IMRT ( CCRT ) . Median follow-up is 37.4 months ( 4.8–66.2 months ) . All patients received a radiation dose of 66Gy/30Fx . In the CCRT group , all patients received a cumulative dose of ≥200 mg/m2 . The differences of 3-year overall survival ( OS ) , 3-year progression-free survival ( PFS ) , 3-year relapse-free survival ( RFS ) , and 3-year metastasis-free survival ( MFS ) between 2 groups were not significant ( P > 0.05 ) . The most frequently increased toxicities related to chemotherapy were mild to moderate leukopenia ( P = 0.003 ) and mild anemia ( P = 0.008).Omission of weekly cisplatin chemotherapy result ed in comparable survival outcomes to CCRT in IMRT population s. More data from future r and omized trials are warranted to further confirm it OBJECTIVES To evaluate the long-term survival and the role of chemotherapy in nasopharyngeal carcinoma ( NPC ) patients in Stage II treated by intensity-modulated radiation therapy ( IMRT ) . METHODS Three hundred and eleven NPC patients in Stage II were review ed . All were treated with IMRT with or without chemotherapy , with 191 , 20 and 100 patients being defined as T1N1M0 , T2N0M0 and T2N1M0 stage , respectively . RESULTS At a median follow-up of 57 months , the 5-year overall survival , disease-specific survival , distant metastasis-free survival , loco-regional relapse-free survival ( LRRFS ) and progression-free survival were 91.1 , 93.5 , 90.6 , 95.9 and 87.6 % , respectively . T2N1 patients had significant poorer survival outcomes than T1N1 patients , with T2N0 patients in between . Further analysis showed that the addition of chemotherapy could only improve LRRFS [ hazard ratio ( HR ) 0.263 , 95 % confidence interval ( CI ) 0.083 - 0.839 , P = 0.024 ] , especially for T1N1 patients ( HR 0.209 , 95 % CI 0.046 - 0.954 , P = 0.043 ) . For those in the T2N1M0 group , chemotherapy , as used in our series , added no benefit to any endpoint . CONCLUSIONS IMRT in NPC patients in Stage II was quite therapeutic ; however , different subgroups have distinct survival outcomes . Distant metastasis was the main failure pattern , especially for those with T2N1 disease , and the chemotherapy currently in use failed to treat sub clinical metastatic foci effectively . Further prospect i ve study is warranted to find out the role and the optimal schedule of chemotherapy in this subgroup of patients To evaluate the long term impact of concurrent chemoradiotherapy ( CCRT ) compared to radiotherapy ( RT ) alone in patients with T2N1M0 nasopharyngeal carcinoma ( NPC ) retrospectively . Three hundred and ninety-two patients with T2N1M0 NPC according to the AJCC 2002 stage classification system were analyzed . Among them , 211 patients were treated with RT alone and the rest of 181 patients were treated with CCRT . A planned dose of 70 Gy was delivered in 2.0 Gy per fraction over 7 weeks to the primary tumor with 6-MV photons or (60)Cobalt γ-ray . The chemotherapy regimen of cisplatin with a dose of 100mg/m(2 ) was delivered for 2 - 3 cycles . With a median follow-up of 66 months ( range 2.4 - 117.1 months ) , the 5-year overall survival ( OS ) and disease-free survival ( DFS ) rates was higher in CCRT group compared to RT alone group , though they failed to reach statistical significance ( 80.2 % vs. 76.6 % , P=0.778 and 70.5 % vs. 64.2 % , P=0.413 , respectively ) . A significant improvement was detected in 5-year relapse-free survival ( RFS ) rate in CCRT group than RT alone group ( 91.5 % vs. 77.3 % , P=0.008 ) . Moreover , chemotherapy was the only independent prognostic factor for the 5-year RFS ( P=0.007 ) . Concurrent chemoradiotherapy appeared to improve the 5-year RFS rate for patients with T2N1M0 NPC . Large prospect i ve , r and omized clinical studies are needed to confirm its therapeutic gain PURPOSE Early-stage nasopharyngeal carcinoma ( NPC ) continues to carry a failure rate of 15 % to 30 % when treated with radiotherapy alone ; the benefit of concomitant radiotherapy and chemotherapy ( CCRT ) in early-stage NPC is unclear . The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT . PATIENTS AND METHODS Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997 , 44 presented with early-stage ( stage I and II ) disease according to the American Joint Committee on Cancer ( AJCC ) 1997 NPC staging system . Twelve of these patients were treated with radiotherapy alone and 32 with CCRT . Each patient 's head and neck area was evaluated by magnetic resonance imaging or computed tomography . Radiotherapy was administered at 2 Gy per fraction per day , Monday through Friday , for 35 fractions for a total dose of 70 Gy . Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy . RESULTS Patients who were treated with radiotherapy alone primarily had stage I disease , whereas none of those who were treated with CCRT had stage I disease ( 11 of 12 patients v none of 32 patients ; P = .001 ) . The locoregional control rate at 3 years for the radiotherapy group was 91.7 % ( median follow-up period , 34 months ) and was 100 % for the CCRT group ( median follow-up period , 44 months ) ( P = .10 ) . The 3-year disease-free survival rate in the radiotherapy group was 91.7 % and was 96.9 % in the CCRT group ( P = .66 ) . CONCLUSION Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT . Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival , compared with stage I patients treated with radiotherapy alone . A prospect i ve r and omized trial is underway to confirm the role of CCRT in stage II NPC |
11,204 | 18,978,801 | We found that simple febrile seizures do not carry a risk of death , but there is a very small risk of death after complex febrile seizures ( CFSs ) , particularly febrile status epilepticus .
There is no evidence that SUDEP ( sudden unexpected death in epilepsy ) occurs in association with febrile seizures .
There is no evidence of any risk of hippocampal or mesial temporal sclerosis ( HS/MTS ) in association with simple febrile seizures . | Approaches to the treatment and investigation of febrile seizures have changed since the main reference studies on outcomes were conducted in the 1960s and 1970s .
We have , therefore , conducted a systematic review of literature from the past 15 years to see whether outcomes have also changed . | BACKGROUND Several disorders have been attributed to measles-mumps-rubella ( MMR ) vaccination during the past decade . The aim of this prospect i ve follow-up study was to identify serious adverse events causally related to MMR vaccination . METHODS When the MMR vaccination program was launched in Finl and in 1982 , a countrywide surveillance system was set up to detect serious adverse events associated with MMR . To obtain detailed case histories vaccinees ' clinical charts were review ed . Serum sample s were analyzed to trace concurrent infections . SETTING All hospitals and health centers in Finl and from 1982 through 1996 . RESULTS Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions cl aim ed to have been caused by MMR vaccination . In all , 77 neurologic , 73 allergic and 22 miscellaneous reactions and 1 death were reported , febrile seizure being the most common event . However , 45 % of these events proved to be probably caused or contributed by some other factor , giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses . CONCLUSIONS Causality between immunization and a subsequent untoward event can not be estimated solely on the basis of a temporal relation . Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases Background : Febrile seizures affect 2 to 4 % of children , and 2 to 10 % develop subsequent unprovoked seizures . Secondary analyses of two large cohorts identified neurodevelopmental abnormalities , complex febrile seizures , and a family history of epilepsy as predictors of unprovoked seizures . We present an analysis of children prospect ively followed from their first febrile seizure to reassess these three factors , examine factors of equivocal importance , and assess the importance of some new factors that we identified as predictors of recurrent febrile seizures . Methods : Children ( N = 428 ) were prospect ively identified for a first febrile seizure through pediatric emergency departments of four hospitals . Information was collected from medical records and interviews with parents . Children were followed for 2 years or more . Results : Unprovoked seizures occurred in 26 ( 6 % ) . Neurodevelopmental abnormalities , complex febrile seizures , and a family history of epilepsy were associated with an increased risk of unprovoked seizures . Recurrent febrile seizures and brief duration of fever before the initial febrile seizure were also risk factors . A family history of febrile seizures , temperature and age at the initial febrile seizure , sex , and race were not associated with unprovoked seizures . Conclusions : We confirmed the increased risk associated with traditionally accepted predictors of epilepsy following febrile seizures . Also , the risk clearly increased with recurrent febrile seizures . In general , predictors of subsequent unprovoked seizures differ from predictors of recurrent febrile seizures . One notable exception , brief duration of fever before the initial febrile seizure , predicts both types of outcome and may be a marker for an increased susceptibility to seizures . NEUROLOGY 1996;47 : 562 - Visual inspection and volumetric analysis of MRIs allow mesial temporal sclerosis ( MTS ) to be reliably identified in patients with temporal lobe epilepsy . The presence of unilateral MTS ipsilateral to the side of habitual seizure onset is an indicator for the prognosis of good outcome after temporal lobe resection . There is evidence to suggest that widespread temporal lobe pathology , leading to atrophy , may be associated with MTS and such abnormal tissue may play an important role in epileptogenesis . We have analysed quantitatively the volumes of the mesial and lateral temporal lobe substructures in MRIs from 62 patients with intractable mesial temporal lobe epilepsy and in 20 normal controls . We found significant atrophy in these structures in patients , ranging from 8.3 to 18.4 % compared with controls . The degree of atrophy in the extrahippocampal structures correlated with the degree of hippocampal atrophy , suggesting that a common process may be responsible . There was no correlation between the degree of atrophy in the extrahippocampal structures and the duration of epilepsy , a history of febrile convulsions or of generalized seizures . These findings suggest that there may be widespread pathological abnormalities in the temporal lobe associated with MTS . The importance of extrahippocampal atrophy to surgical outcome and whether it occurs in temporal lobe epilepsy not associated with MTS remain to be investigated A cohort of 92 children with an initial febrile convulsion ( FC ) , prospect ively identified in a community-based study 1985 - 1987 , was compared with a cohort of 185 age- and sex-matched referents from the same study area . The median time of follow-up was 6.7 years ( range : 5.7 - 7.7 ) and the median age at follow-up was 8.3 years ( range 6.5 - 14 ) . The cases had their first FC at a median age of 18 months ( range 5 - 67 months ) , their second FC at 24 months ( 11 - 108 months ) and their third FC at 26 months ( 13 - 92 months ) . FC recurred in 42 % of the FC cohort , and 3.8 % of the children in the referent cohort experienced FC . Single or recurrent afebrile seizures occurred in 4.3 % and epilepsy in 3.3 % of the FC cohort , while no afebrile seizures occurred in the referent cohort . The risk of having a sibling with FC was three times ( 95 % confidence interval 1.3 - 6.2 ) higher in the FC cohort , while there was no difference between the cohorts in the risk of siblings developing afebrile seizures . There was no difference between the cohorts in the utilization of health services during the follow-up period . Two children in the FC cohort went to a school for the mentally retarded . There was no aetiological relationship between the FC and the mental retardation in these cases . All other children attended normal schools and none needed remedial instruction Abstract Objective : To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures . Design : Prospect i ve r and omised study . Setting : Paediatric emergency department in a general hospital . Subjects : 47 children aged six months to five years with prolonged febrile seizure ( at least 10 minutes ) during a 12 month period . Interventions : Intranasal midazolam ( 0.2 mg/kg ) and intravenous diazepam ( 0.3 mg/kg ) . Main outcome measures : Time from arrival at hospital to starting treatment and cessation of seizures . Results : Intranasal midazolam and intravenous diazepam were equally effective . Overall , 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam . The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group ( 3.5 ( SD 1.8 ) minutes , 95 % confidence interval 3.3 to 3.7 ) than the diazepam group ( 5.5 ( 2.0 ) , 5.3 to 5.7 ) . The mean time to control of seizures was significantly sooner ( 6.1 ( 3.6 ) , 6.3 to 6.7 ) in the midazolam group than the diazepam group ( 8.0 ( 0.5 ) , 7.9 to 8.3 ) . No significant side effects were observed in either group . Conclusion : Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam , although midazolam was as safe and effective as diazepam . The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam . The intranasal route can possibly be used not only in medical centres but in general practice and , with appropriate instructions , by families of children with recurrent febrile seizures at home In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospect i ve study in two groups of children ; Group A : 45 children ( 25 female , 20 male ) , receiving oral prophylaxis with diazepam , and Group B : 65 children ( 35 female , 30 male ) who did not receive any oral prophylaxis . All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years . Among the patients of Group A , recurrent febrile seizures ( FS ) occurred in five of the 45 children ( 11.1 % ) . Among the 65 children of Group B , 20 ( 30.7 % ) went on to have one or more additional episodes . In conclusion , our study demonstrates that oral diazepam , given only when fever is present , is an effective means of reducing the risk of recurrences of FS Febrile status epilepticus ( SE ) represents the extreme end of the complex febrile seizure spectrum . If there are significant sequelae to febrile seizures , they should be more common in this group . We have prospect ively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx , New York , and Richmond , Virginia . They were compared with 244 children who presented with their first febrile seizure ( not SE ) in a prospect i ve study done in the Bronx . The mean age of the children with febrile SE was 1.92 years , and of the comparison group , 1.85 years . Duration of SE was 30 - 59 min in 103 ( 58 % ) , 60 - 119 min in 43 ( 24 % ) , and > or = 120 min in 34 ( 18 % ) . Focal features were present in 64 ( 35 % ) of cases . There were no deaths and no cases of new cognitive or motor h and icap . Children with febrile SE were more likely to be neurologically abnormal ( 20 % vs. 5 % ; p < 0.001 ) , to have a history of neonatal seizures ( 3 % vs. 0 ; p = 0.006 ) and a family history of epilepsy ( 11 % vs. 5 % ; p = 0.05 ) and less likely to have a family history of febrile seizures ( 15 % vs. 27 % ; p = 0.01 ) than were children in the comparison group . The short-term morbidity and mortality of febrile SE are low . There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures . Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis Summary : Purpose : A prospect i ve population ‐based case‐control study was performed to ascertain whether febrile convulsion ( FC ) in early childhood is associated with neurocognitive attention deficits in school age We report a 12-year follow-up study of children with febrile convulsions ( FCs ) . The National General Practice Study of Epilepsy ( NGPSE ) is a large prospect i ve community-based cohort study of 1,195 patients of all ages from first presentation with an identified seizure . Two hundred and twenty children with a first febrile convulsion were identified from the above study between 1984 and 1987 . Children were prospect ively followed up to ascertain subsequent seizures , neurological problems and treatment . Two hundred and seven patients were followed for a minimum of 8.4 years ( median 11.2 years ) . In the FC cohort , 6 % of the children developed subsequent epilepsy , which compares with a population risk of about 1.4 % . Ten percent had neurological sequelae . Eleven percent of the children had received medication to prevent recurrence of FC , and in one third of these cases , this was for simple FCs . Using a time-dependent covariate Cox proportional hazards model , the number of FCs was associated with an increased risk of epilepsy ( hazard ratio 2.48 ; 95 % confidence limits , CL 1.68 , 3.65 ) up to a limit of 4 . A statistically significant association between occurrence of complex FC and subsequent epilepsy was not found , but a review of other studies quantified the odds ratio for epilepsy after a complex first FC as 3.4 ( 95 % CL 2.1 , 5.4 ) . Epilepsy is a significant if infrequent sequel to FCs . Factors associated with subsequent epilepsy are the number of FCs or a complex first FC . Overtreatment of this condition continues Interictal diffusion imaging studies in patients with medial temporal lobe epilepsy ( MTLE ) accompanied by hippocampal sclerosis ( HS ) have shown an increased diffusivity in the epileptogenic hippocampus . In this study , we wanted to explore the whole brain in order to determine if MTLE could have an impact on the organization and the architecture of a large cerebral network and to identify clinical factors that could mediate diffusion abnormalities . Diffusion tensor imaging ( DTI ) and statistical parametric mapping of the entire brain were performed in 35 well-defined MTLE patients and in 36 healthy volunteers . SPM analyses identified three abnormal areas : an increased diffusivity was detected in the epileptic hippocampus and the ipsilateral temporal structures associated with a decreased anisotropy along the temporal lobe , a decreased diffusivity was found in the contralateral non-sclerotic hippocampus , the amygdala , and the temporal pole , and finally , a decreased anisotropy was noted ipsilaterally in posterior extratemporal regions . Duration of epilepsy , age at onset , and the frequency of generalized tonic-clonic seizures or partial complex seizures did not correlate with the presence of diffusion abnormalities . Region of interest analysis in the hippocampus/parahippocampus demonstrated a correlation between lower ipsilateral diffusivity values and occurrence of epigastric aura and between higher anisotropy values in both hemispheres and history of febrile seizures . In conclusion , this study showed that diffusion abnormalities are not restricted to the pathologic hippocampus and involve a larger network . This pattern may indirectly reflect the epileptogenic network and may be interpreted as a cause or a consequence of epilepsy BACKGROUND There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy . Some of the existing studies may be biased because of patient selection and limitations in determining predisposition . OBJECTIVE To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy . PATIENTS AND METHODS We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up . Risk factors for epilepsy were determined prospect ively on at least 3 occasions before anterior temporal lobectomy . Risk factors investigated were a history of febrile convulsions , family history of epilepsy , significant head trauma , history of meningitis , history of encephalitis , or significant perinatal insult . Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings ( hippocampus and lesion ) . Outcome was determined using Engel 's classification . For statistical analysis we used successive logistic regression analysis , chi(2 ) test , Fisher exact test , and t test . RESULTS Of the 102 patients , 13 had no identified risk factor for epilepsy , 49 had 1 identified risk factor , and 40 had more than 1 . Frequencies were 39 febrile convulsions ( 15 complex febrile convulsions ) , 29 head trauma , 22 with lesions seen on magnetic resonance imaging , 12 history of meningitis , 2 history of encephalitis , 19 family history of epilepsy , and 4 perinatal insult . Seventy-one ( 70 % ) were classified as Engel 's class I , with 56 patients continuously free of seizures at follow-up . Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor ( P = .27 ) . No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy , but the presence of head trauma , alone or in combination , was correlated with continued seizures following anterior temporal lobectomy ( P = .03 ; odds ratio , 2.6 ) . Better outcomes were not seen in those with head trauma before the age of 5 years ( P = .57 ) . These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis . Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others ( P = .82 ) . CONCLUSIONS Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy . No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures . This information may be used in preoperative counseling of patients Controversy exists as to whether hippocampal sclerosis ( HS ) is a preexisting cause or a consequence of seizures . We investigated 122 consecutive patients who underwent anterior temporal lobectomy for intractable epilepsy between 1989 and 1992 . MRI scans were normal apart from evidence of HS in 5 cases . The degree of HS was grade d from 0 to 4 . There was a significant inverse correlation between age of seizure onset and grade of HS ( P < 0.0001 ) , and a positive correlation between duration of epilepsy and grade of HS ( P < 0.001 ) . Using a dichotomous grouping of HS ( HPSC - for grade s 0 and 1 [ no/mild HS ] , and HPSC + for grade s 3 and 4 [ moderate/marked HS ] ) , there was a positive correlation between HPSC + and a history of childhood febrile seizures ( CFS ) ( P = 0.003 ) , earlier age of onset of epilepsy ( P < 0.001 ) and longer duration of epilepsy ( P < 0.001 ) . There was no correlation with history of particularly prolonged individual seizures . Partial correlations after controlling for age at onset of epilepsy showed that there was no longer a significant relationship between HPSC + and duration of epilepsy . After controlling for duration of epilepsy , the relationship between HPSC + and age of onset remained significant ( P < 0.001 ) . The correlation between HPSC + and CFS , controlling for age at onset , was not significant . A series of logistic regression analyses showed age at onset to be the only predictor of HPSC + . It is concluded that this is supportive evidence for preexisting HS being a cause of temporal lobe epilepsy and not a consequence of seizures Purpose : A history of febrile convulsions ( FC ) is often obtained in patients presenting for surgical treatment of temporal lobe epilepsy ( TLE ) , but it is not clear that preferential temporal localization of epilepsy is associated with antecedent FC . Methods : We prospect ively inquired about FC and their characteristics in all patients presenting to an epilepsy clinic through a patient question naire and interview . We studied the incidence of antecedent childhood febrile convulsions in relation to epilepsy diagnosis . Results : FC were reported by 133 of 1005 study patients ( 13.2 % ) . TLE was more likely to be preceded by FC ( 78/310 , 25.2 % ) than extratemporal epilepsy (ETE)(12/216 , 5.6 % ) ( p < 0.000001 ) or generalized epilepsy (GE)(16/146 , 11.0 % ) ( p < 0.001 ) . Patients with GE were more likely than patients with TLE to have had simple FC ( p < 0.00005 ) . Prolonged duration was the most common FC complex feature in TLE patients . Conclusions : We demonstrated a preferential association of FC with temporal lobe foci and a weaker association between FC and GE . FC does not appear to be a clear risk factor for ETE PURPOSE The success of epilepsy surgery in temporal lobe epilepsy reaches a 64 % rate of seizure freedom , based on a r and omized control trial . Observational studies from epilepsy centers worldwide indicate seizure freedom rates up to 93 % when the etiology is unilateral hippocampal sclerosis . Several risk factors are attributed to the recurrence of seizures following the surgical procedure . Nonetheless , whether race influences the outcome of temporal lobe surgery is unknown . The purpose of this study was to evaluate if race plays a role in outcome following surgery . METHODS Data were obtained from the discharge data base of the University of Alabama at Birmingham video/EEG monitoring unit , between 1998 and 2003 , as well as the clinical charts . Seizure recurrence was evaluated 1 year following surgery . The sample consisted of all patients with a primary diagnosis of mesial temporal sclerosis ( MTS ) who underwent anterior temporal lobectomy . Multiple logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for MTS . Two sets of logistic regression models were estimated to generate odds ratios ( ORs ) for seizure recurrence after an anterior temporal lobectomy for African-Americans or other possible ethnic/racial group present relative to non-Hispanic Caucasians . The first model incorporated only ethnicity as the independent variable and generated unadjusted ORs for seizure recurrence following the surgical procedure . The second set included the independent variables : duration of epilepsy , history of febrile seizures , lateralization of epileptogenic focus , h and edness , and age . RESULTS Seventy patients underwent surgical treatment and all of them had pathologic confirmation of MTS . Follow-up information for six was not available . Analysis of the remaining 64 patients revealed that African-Americans were more likely than non-Hispanic Caucasians to have seizure recurrence after surgery ( OR=2.1 , 95 % CI=0.6 - 8.0 ) . After potential confounders ( duration of epilepsy , history of febrile seizures , lateralization of epileptogenic focus , h and edness , and age ) were controlled , this finding did not change ( OR=1.7 , 95 % CI=0.3 - 10.7 ) . CONCLUSION Our data suggest that race may be an important factor related to seizure outcome following temporal lobectomy BACKGROUND Phenobarbital , once widely prescribed to prevent febrile seizures , is now in disfavor because of its side effects and lack of efficacy . Diazepam , administered only during episodes of fever , may be a safe , effective agent to prevent the recurrence of febrile seizures . METHODS We conducted a r and omized , double-blind , placebo-controlled trial among 406 children ( mean age , 24 months ) who had at least one febrile seizure . Diazepam ( 0.33 mg per kilogram of body weight ) or placebo was administered orally every eight hours during all febrile illnesses . RESULTS During a mean follow-up of 1.9 years ( a period during which 90 percent of febrile seizures recur ) , our intention-to-treat analysis showed a reduction of 44 percent in the risk of febrile seizures per person-year with diazepam ( relative risk = 0.56 ; 95 percent confidence interval , 0.38 to 0.81 ; P = 0.002 ) . A survival analysis of the length of time to the first recurrent febrile seizure did not show a significant difference between the treatment groups ( P = 0.064 by the log-rank test ) , but after adjustment for covariates , diazepam was found to have a benefit ( P = 0.027 by Cox regression analysis ) . An analysis restricted to children who had seizures while actually receiving the study medication ( 7 in the diazepam group and 29 in the placebo group ) showed an 82 percent reduction in the risk of febrile seizures with diazepam ( relative risk = 0.18 ; 95 percent confidence interval , 0.09 to 0.37 ; P < 0.001 ) . Of the 153 children who took at least one dose of diazepam , 39 percent had ataxia , lethargy , or irritability or at least one other moderate side effect that was reversed after a reduction in the dose . There were no severe side effects . CONCLUSIONS Oral diazepam , given only when fever is present , is safe and reduces the risk of recurrent febrile seizures In order to identify the brain lesions of symptomatic/cryptogenic partial epilepsies ( S/CPEs ) in infants and children , magnetic resonance imaging ( MRI ) studies , thorough encephalographic ( EEGic ) studies , and detailed clinical and neurologic evaluations were obtained in 300 infants and children who were diagnosed to have S/CPEs with onset before the age of 13 years during the past 7 years . The overall detection rate of brain lesions by MRI was 41.7 % ( 125/300 ) . Congenital malformations ( 18 cases ) , vascular malformations ( 9 cases ) , neurocutaneous syndromes ( 13 cases ) , and space-taking lesions ( 20 cases ) constitute a large percentage of SPEs in infants and children . A variety of insults such as infection , ischemia , hemorrhage , trauma and metabolic disorders can result in destructive parenchymal loss lesions including porencephaly , focal atrophy , hemiatrophy , and diffuse brain atrophy ( 20 cases ) . Major etiologic factors leading to infa rct ion , encephalomalacia , leukomalacia , included trauma , hvpoxicischemic encephalopathy ( HIE ) , systemic lupus erythematosus ( SLE ) , encephalitis , vasculitis , venous thrombosis , vasculopathies , and heart problems ( 22 cases ) . Mesial temporal sclerosis ( MTS ) could be evidence d in around 20 % ( 18/95 ) of cases with temporal lobe epilepsy ( TLE ) , which was strongly associated with past histories of febrile seizures and encephalitis complicated by status epileptics . However , cases with porencephaly , global atrophy or delayed myelination of unilateral temporal lobe on MRI were more related to HIE . With the advent of neuroimaging techniques , particularly MRI , a wide variety of underlying pathology can be detected as a cause of symptomatic partial epilepsies in pediatric patients . The occurrence of S/CPE indicates the presence of localized brain dysfunction , and many of the causes are potentially treatable . An orderly and thorough clinical and laboratory investigations , as well as neuroimaging studies should be made to diagnose and treat any underlying conditions OBJECT The syndrome of medial temporal lobe epilepsy ( MTLE ) may occur in patients in whom magnetic resonance ( MR ) images demonstrate normal findings . In these patients , there is no evidence of hippocampal sclerosis on neuroimaging , and histopathological examination of the resected hippocampus does not reveal significant neuron loss . In this paper the authors describe the distinct clinical features of this MTLE subtype , referred to as paradoxical temporal lobe epilepsy ( PTLE ) . METHODS The authors selected 12 consecutive patients with preoperative findings consistent with MTLE in whom MR imaging did not demonstrate any hippocampal abnormality . Onset of hippocampal seizure was confirmed by long-term intracranial monitoring . There were six female and six male patients with a mean age of 32 + /- 11 years , ( mean + /- st and ard deviation [ SD ] ) at presentation . These patients ' seizure histories , available hippocampal volumetric measurements , and hippocampal cell densities in different subfields were review ed . Sharp electrode recordings from dentate granule cells that had been maintained in hippocampal slices provided a measure of excitation and inhibition in the tissue . We compared these data with those of a cohort of 50 r and omly selected patients who underwent anteromedial temporal resection for medial temporal sclerosis ( MTS ) during the same time period ( 1987 - 1999 ) . The duration s of follow up ( means + /- SDs ) for the PTLE and MTS groups were 51 + /- 59 months and 88 + /- 44 months , respectively . A history of febrile seizure was present less frequently in the PTLE group ( 8 % ) than in the MTS group ( 34 % ) . Other risk factors for epilepsy such as trauma , meningoencephalitis , or perinatal injuries were present more frequently in the PTLE group ( 50 % ) than in the MTS cohort ( 36 % ) . In patients in the PTLE group the first seizure occurred later in life ( mean age at seizure onset 14 years in the PTLE group compared with 9 years in the MTS group , p = 0.09 ) . Ten patients ( 83 % ) in the PTLE cohort and 23 patients ( 46 % ) in the MTLE cohort had secondary generalization of their seizures . Among patients with PTLE , volumetric measurements ( five patients ) and r and omized blinded visual inspection ( seven patients ) of the bilateral hippocampi revealed no atrophy and no increased T2 signal change on preoperative MR images . All patients with PTLE underwent anteromedial temporal resection ( amygdalohippocampectomy , in five patients on the left side and in seven on the right side ) . Electrophysiological studies of hippocampal slices demonstrated that dentate granule cells from patients with PTLE were significantly less excitable than those from patients with MTS . The mean pyramidal cell loss in the CAI subfield in patients in the PTLE group was 20 % ( range 0 - 59 % ) and that in patients in the MTS group was 75 % ( range 41 - 90 % ) ( p < 0.001 ) . Maximal neuron loss ( mean loss 38 % ) occurred in the CA4 region in six patients with PTLE ( end folium sclerosis ) . At the last follow-up examination , six patients ( 50 % ) in the PTLE group were seizure free compared with 38 patients ( 76 % ) in the MTS group . CONCLUSIONS Clinical PTLE is a distinct syndrome with clinical features and surgical outcomes different from-those of MTS A cohort of 289 children with febrile convulsions who had been r and omised in early childhood to either intermittent prophylaxis ( diazepam at fever ) or no prophylaxis ( diazepam at seizures ) was followed up 12 years later . The study focused on the occurrence of epilepsy and on neurological , motor , intellectual , cognitive , and scholastic achievements in the cohort . At follow up the two groups were of almost identical age ( 14.0 v 14.1 years ) , body weight ( 58.2 v 57.2 kg ) , height ( 168.2 v 167.7 cm ) , and head circumference ( 55.9 v 56.2 cm ) . The occurrence of epilepsy ( 0.7 % v 0.8 % ) , neurological examination , fine and gross motor development on the Stott motor test , intellectual performance on the Wechsler intelligence scale for children verbal IQ ( 105 v 105 ) , performance IQ ( 114 v 111 ) , and full scale IQ ( 110 v 108 ) , cognitive abilities on a neuropsychological test battery , including short and long term , auditory and visual memory , visuomotor tempo , computer reaction time , reading test , and scholastic achievement were also very similar . Children with simple and complex febrile convulsions had the same benign outcome . The long term prognosis in terms of subsequent epilepsy , neurological , motor , intellectual , cognitive , and scholastic ability was not influenced by the type of treatment applied in early childhood . Preventing new febrile convulsions appears no better in the long run than abbreviating them Temporal lobe epilepsy ( TLE ) is frequently associated with hippocampal sclerosis ( HS ) and a history of febrile convulsions ( HFC ) . The authors investigated 292 patients with TLE due to HS . Left HS occurred more frequently ( 57 % ) than right HS ( 43 % , p = 0.01 ) . Forty-seven percent of the patients had HFC . In patients with right HS , HFC occurred in 59.6 % , whereas in patients with left HS , HFC was present in 37.5 % , showing a highly significant lateralization difference We evaluated whether mesial temporal lobe epilepsy ( MTE ) and neocortical temporal lobe epilepsy ( NTE ) can be distinguished on electro clinical grounds . One hundred and twenty-two consecutive MTE ( n = 86 ) and NTE ( n = 36 ) patients were included in this prospect i ve study . All patients underwent prolonged EEG-video monitoring and high resolution magnetic-resonance imaging ( MRI ) . MTE was defined as epilepsy with purely mesial temporal lesion in the absence of extramesial temporal pathology , based on pre-operative MRI or post-operative histology . NTE was defined as neocortical temporal MRI lesions , depth recorded neocortical temporal seizure onset and lack of mesial temporal lesions on MRI or histology . One thous and two hundred and fourty-nine epileptic seizures were analyzed . Congenital malformation ( NTE 19 % versus MTE 3 % , P < 0.01 ) , nonspecific auras ( NTE 25 % versus MTE 8 % , P < 0.001 ) and early clonic activity following automatisms ( NTE 22 % versus MTE 8 % , P < 0.03 ) were more frequent in NTE . In contrast , a history of febrile seizures ( MTE 29 % versus NTE 3 % , P < 0,001 ) , abdominal auras ( MTE 62 % versus NTE 33 % , P < 0.005 ) and contralateral h and dystonia ( MTE 43 % versus NTE 22 % , P < 0.03 ) were more often documented in MTE . Interictal epileptiform discharges in MTE occurred predominantly ( > 67 % ) over the ipsilateral mesial temporal regions ( MTE 65 % versus NTE 33 % , P < 0.001 ) . No MTE patient had lateral neocortical temporal spike predominance ( NTE 22 % , P < 0.001 ) . Multiple logistic regression revealed that a history of febrile seizures , abdominal auras , contralateral dystonic posturing and predominance of ipsilateral mesial temporal spikes point to MTE , with an accuracy of 73 % ( PPV 81 % , NPV 70 % ) . Analyzing clinical and EEG features , particularly the distribution of interictal epileptiform discharges , helps to differentiate between MTE and NTE After their first febrile seizure , 180 children were prospect ively monitored to provide data for a quantitative and qualitative analysis of the factors affecting the risk of recurrence of febrile seizures and to evaluate the influence of recurrences on the outcome . Of these children , 153 had subsequent febrile episodes and were included in the risk-factor analysis . The outcome was evaluated after a 2-year follow-up in 156 children . Each febrile episode increased the risk of recurrence by 18 % . Each degree of increase in temperature ( Celsius ) during subsequent infections almost doubled the risk of recurrence . Age , sex , the type of initial seizure , the temperature during the initial seizure , or a family history of febrile seizures or epilepsy did not influence the recurrence rate significantly . The results indicate that procedures that minimize the probability of febrile infections would decrease the risk of recurrences of febrile seizures Objective : To analyze clinical , electrophysiologic , and neuroradiologic characteristics of a group of patients with nonlesional intractable temporal lobe epilepsy ( TLE ) and rare or absent interictal epileptiform abnormalities ( IEA ) . Methods : Between 1990 and 2000 , 31 patients ( 11 men ; mean ± SD age 34.3 ± 11.7 years ) with nonlesional intractable TLE were consecutively selected on the basis of the absence or paucity of IEA ( < 1/h ) on serial scalp EEG recording ; these were defined as “ oligospikers . ” The clinical and laboratory characteristics of oligospikers were compared with those of a group of 27 age-matched control subjects ( 10 men ; mean ± SD age 38.5 ± 11 years ) , r and omly selected from a pool of patients with nonlesional TLE with frequent IEA . Results : Oligospikers showed a later age at seizure onset ( mean ± SD 19.1 ± 14.4 versus 10.2 ± 7.4 years ; p = 0.004 ) , lower monthly frequency of complex partial seizures ( median 6 versus 12 ; p = 0.035 ) , lower incidence of secondarily generalized tonic-clonic seizures ( 10 versus 81 % ; p < 0.001 ) , and no status epilepticus ( 0 versus 22 % ) than control subjects . Also , hippocampal atrophy ( HA ) was less commonly found in oligospikers ( 55 versus 96 % ; p = 0.001 ) . However , there were no differences between the two groups in the frequency of family history of epilepsy , risk factors , febrile convulsions , and type of medication . Twenty-three ( 74 % ) oligospikers and 25 ( 93 % ) control patients underwent either a selective amygdalohippocampectomy or corticoamygdalohippocampectomy . Excellent surgical outcome ( Engel ’s Class Ia ) was found in 14 of 23 ( 61 % ) oligospikers and 17 of 25 ( 67 % ) control patients . Conclusions : This study identified a subgroup of patients with nonlesional intractable TLE with no or few IEA . Oligospikers have a later age at seizure onset , less frequent and less severe seizures , besides a lower incidence of HA . The similarity of etiologic factors compared with patients with frequent IEA suggests that the rarity of spikes could reflect a disease not really distinct but less severe , even though still intractable and incapacitating enough to consider surgery . In spite of the absence or paucity of IEA , oligospikers have excellent surgical outcome Patients with epilepsy may be subject to an increased risk of premature death from the underlying cause , or from the epilepsy itself . The extent and nature of this risk has been insufficiently investigated . St and ard mortality ratios ( SMRs ) of patients with newly diagnosed epilepsy were determined in a prospect i ve national population -based study . 1091 patients with newly diagnosed or suspected epilepsy were ascertained who were attending one of 275 UK general practice s from 1984 - 1987 . 1091 patients were classified after 6 months as definite epilepsy ( 564 ) , possible epilepsy ( 228 ) , febrile seizures ( 220 ) , or not epilepsy ( 79 ) . Over a median follow up of 6.9 years the SMR for patients with definite or possible epilepsy was 2.5 ( 95 % CI 2.1 - 2.9 ) , and 3.0 ( 2.5 - 3.7 ) for definite epilepsy . The SMR was highest during the first year after diagnosis 5.1 ( 3.8 - 6.5 ) , declined to 2.5 ( 1.5 - 3.9 ) at 3 years , and 1.3 ( 0.7 - 2.0 ) at 5 years . The commonest causes of death were pneumonia ( SMR 7.2 ) , cancer ( 3.5 ) , and stroke ( 3.7 ) . The SMR for patients with idiopathic epilepsy was 1.6 ( 1.0 - 2.4 ) , remote symptomatic epilepsy 4.3 ( 3.3 - 5.5 ) , and acute symptomatic epilepsy 2.9 ( 1.7 - 4.5 ) . Mortality in patients with newly-diagnosed epilepsy was high , mainly due to the underlying cause . The SMR for idiopathic epilepsy was also raised , suggesting that epilepsy per se may carry a small risk of death PURPOSE To study the relationship of complex febrile seizures ( CFS ) in the evolution of mesial temporal sclerosis . METHODS We studied five children 22 - 68 ( mean 44 ) months old with MRI volumetry 2 days-46 months after their first CFS , and compared total hippocampal volumes and right to left hippocampal volume ratios to those of 11 controls , 15 - 83 ( mean 55 ) months old , who had MRI for complaints which turned out to be neurologically insignificant . RESULTS In control children , total hippocampal volumes increased linearly with age , while right to left hippocampal volume ratios tended to decrease with age . In children with CFS total hippocampal volumes tended to be smaller than in controls . Right to left ratios were greater than 1 in all five children with CFS compared to seven of 11 controls . Hippocampal asymmetry was noted in only one child , with the right to left volume ratio exceeding two st and ard deviations from the control mean . The MRI of this child also demonstrated a subarachnoid cyst in the left fronto central region , ipsilateral to the smaller hippocampus . Visual inspection of the remaining patients revealed no definite structural cortical abnormalities . None of the children developed subsequent afebrile seizures during the brief follow-up period . CONCLUSIONS Hippocampal volumetry in controls revealed a linear increase in total hippocampal volumes and a statistically nonsignificant trend toward reduced right larger than left hippocampal ratios between 17 and 83 months old . The tendency for smaller total hippocampal volumes and larger right to left hippocampal volume ratios in children with CFS compared to controls could suggest a developmental abnormality , injury during CFS , or be age-related . The significant hippocampal asymmetry in a single child with CFS suggests that age may not be a factor in every case . Further studies are needed to collect control data in young children as well as prospect ively follow children with CFS with serial imaging to better underst and the relationship between CFS and the evolution of hippocampal atrophy The predictive value of magnetic resonance imaging ( MRI ) was assessed by a prospect i ve study of 34 patients selected for surgical treatment of temporal lobe epilepsy . The MRIs were interpreted using st and ardized visual diagnostic criteria and the imaging findings were correlated with the surgical outcome . Lateralized MRI abnormalities were found in 25 ( 74 % ) of 34 patients . Significant associations were found between either the presence of a restricted foreign-tissue lesion or hippocampal atrophy and an excellent surgical outcome . An abnormal MRI had an 82 % predictive value and a normal MRI had a 56 % predictive value for surgical success . A history of febrile convulsions and the presence of hippocampal atrophy best predicted outcome ( predictive value , 86 % ) . These results suggest that specific MRI findings in c and i date s for temporal lobe epilepsy surgery are predictive of surgical outcome . The information provided by MRI may be of value for counseling patients prior to surgical intervention |
11,205 | 23,223,753 | Variability in quality of care between setting s can easily be overshadowed by variability in data quality .
However , the use of DHDD by physicians to evaluate their own medical practice may be useful .
But only if physicians are willing to critically interpret the meaning of the information for their medical practice assessment | OBJECTIVES We performed a systematic review to investigate the quality of diagnostic hospital discharge data ( DHDD ) in order to gain insight in the usefulness of these data for medical practice assessment .
We investigated the methods used to evaluate data quality , factors that determine data quality and its consequences for medical practice assessment . | Background : The aim was to analyse the magnitude , direction and predictors of change in the main hospital discharge diagnosis ( HDD ) after a clinical expert review , among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases . Methods : A total of 602 patients with a suspicion diagnosis of pancreas cancer ( PC ) , cancer of the extrahepatic biliary system ( CEBS ) or benign biliopancreatic pathologies ( BPP ) were prospect ively recruited at five general hospitals . A structured form was used to collect information from medical records . A panel of experts revised all diagnostic information and established the main clinico-pathological diagnosis ( CPD ) by consensus . Results : Of the 204 cases with a HDD of PC , 176 ( 86 % ) were deemed to have a CPD of PC , eight of CEBS , twelve a neoplasm of different origin , four BPP and four syndromic diagnoses . Thus , 28 cases ( 14 % ) were false positives . Of the 129 patients with a HDD of CEBS , 15 ( 12 % ) were false positives . Nine of the 396 cases with a HDD of non-PC ( 2 % ) had a CPD of PC ( false negatives ) , whilst 14 of 471 patients with a HDD of non-CEBS ( 3 % ) were deemed to have CEBS . Overall , sensitivity and specificity of HDD for PC were , respectively , 95 and 93 % , and for CEBS , 89 and 97 % . Cytohistological confirmation and laparotomy were independent predictors of diagnostic change . Conclusions : Validity of the HDD was high , but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results , and highlights the need to review all HDDs . Alternatively , only patients at high risk of misdiagnosis could be review ed : primarily , those lacking a cytohistological diagnosis or a laparotomy . No exclusions appear warranted solely on the basis of age , gender or tumour spread Clinical data repositories represent a potential gold mine of information and knowledge . Rapid access to such information can help bridge the gap between clinical care and research , support clinical and executive decision making , and improve the quality of care . A clinical data base can be used in four ways : to display information about an individual patient ( results reporting ) ; to find data on a patient with similarities to one being seen ( case finding ) ; to describe a group of patients with at least one attribute in common ( cohort description ) ; and to analyze data patterns in terms of trends or relationships ( predictive modeling ) . It seems unlikely that many important clinical questions will be subject to r and omized clinical trials because of the ethics , logistics , and expense that would be involved . Evolving statistical and epidemiological methods allow us to approach these clinical data repositories with the purpose of building predictive models , but a clear underst and ing of the limitations of routinely collected clinical data and the inherent biases is necessary . The largest barrier to using routinely collected clinical data is not the limitations of the data themselves , but rather the lack of a data paradigm for the decision-maker . We present some of the problems and pitfalls in obtaining and using routinely collected data , based upon the use of ClinQuery at Boston 's Beth Israel Hospital and the re sources and traditions at the Mayo Clinic Information on coronary heart disease ( CHD ) obtained from the Finnish Hospital Discharge and Cause-of-Death Registers was compared with that collected in the Helsinki Heart Study ( HHS ) during an 8.5-year follow-up . The purpose of the comparison was two-fold , firstly , to study the accuracy of registration of CHD and secondly , to find out what diagnostic codes to use for CHD in register-based follow-up studies . The HHS cases were used as the ' golden st and ard ' and the CHD deaths and definite nonfatal acute myocardial infa rct ions ( AMIs ) ( all diagnoses ) were taken from the registers to establish the sensitivity of the Hospital Discharge and Cause-of-Death Registers combined . The sensitivity was 0.84 during the period 1980 - 86 and 0.87 during 1987 - 90 , with the positive predictive values 0.94 and 0.92 respectively . The treatment effects seen in the HHS were compared with the effects that would have emerged , if register-based information only had been used with different definitions of CHD . Of the register-based calculations , the one with the definition ' all CHD deaths and hospitalizations with the ICD-8 code 410 ' came closest to the HHS result , with a 32 % reduction ( P=0.028 one-sided ) of CHD incidence , while the original HHS result was a 34 % reduction ( P=0.008 one sided ) . However , when comparing Kaplan-Meier plots of cumulative hazards of CHD , the plot with a wider definition of CHD ( ICD-8 and ICD-9 codes 410 - 414 ) came closest to the HHS experience , especially if revascularizations were included in the latter . Definite AMI as a single definition of CHD might thus not be sufficient when study ing CHD risk , instead , at least two parallel definitions of CHD should be used OBJECTIVE : To assess the validity of obstetric complications , including the Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) Core Measure on perineal lacerations , in the California Patient Discharge Data Set . METHODS : We r and omly sample d 1,611 deliveries from 52 of the 267 hospitals that performed more than 678 eligible deliveries in California in 1992–1993 . We compared hospital-reported complications against our recoding of the same records . RESULTS : Third- and fourth-degree perineal lacerations were reported accurately , with estimated sensitivities exceeding 90 % and positive predictive values exceeding 65 % ( weighted to account for the stratified sampling design ) or 85 % ( unweighted ) . Based on in-depth review of discrepant cases , we estimate the actual positive predictive value at over 90 % . Most coding discrepancies were between no injury and first degree , or between first and second degree . Most postpartum complications , including urinary tract and wound infections , endometritis , anesthesia complications , and postpartum hemorrhage were reported with less than 70 % sensitivity , but at least 80 % positive predictive value . Composite measures from Health Grade s and Solucient , which include these complication codes , also suffer from high false-negative rates . CONCLUSION : Third- and fourth-degree perineal lacerations are accurately reported on hospital discharge abstract s , confirming the validity of related quality indicators sponsored by the Agency for Healthcare Research and Quality and JCAHO . Administrative data seem less useful for monitoring other in-hospital postpartum complications . LEVEL OF EVIDENCE : In order to measure the coverage and accuracy of the Hospital In-patient Enquiry Scheme data in a large acute hospital in Dublin , 793 patient charts were selected r and omly from all the discharges in 1990 . The capture rate was 56 % . Whether a diagnosis was captured for the Hospital In-patient Enquiry Scheme depended partly upon geographical factors within the hospital and partly upon the nature of the diagnosis . " Non-capture " was not r and om and was particularly likely to occur where the case was complex , e.g. oncology , HIV infection . The coding accuracy of primary diagnoses was 59 % and the completeness of recording of secondary diagnoses was 56 % . Both were significantly associated with the presence in the hospital chart of discharge summaries and with the clarity and source of written diagnoses . The factors that affected accuracy were not the same as those affecting the capture rate BACKGROUND Concept-based Indexing is purported to provide more granular data representation for clinical records.1,2 This implies that a detailed clinical terminology should be able to provide improved access to clinical records . To date there is no data to show that a clinical reference terminology is superior to a precoordinated terminology in its ability to provide access to the clinical record . Today , ICD9-CM is the most commonly used method of retrieving clinical records . OBJECTIVE In this study , we compare the sensitivity , specificity , positive likelihood ratio , positive predictive value and accuracy of SNOMED-RT vs. ICD9-CM in retrieving ten diagnoses from a r and om sample of 2,022 episodes of care . METHOD We r and omly selected 1,014 episodes of care from the inpatient setting and 1,008 episodes of care from the outpatient setting . Each record had associated with it , the free text final diagnoses from the Master Sheet Index at the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the episode of care . The free text diagnoses were coded by two expert indexers ( disagreements were addressed by a Staff Clinician ) as to whether queries regarding one of 5 common or 5 uncommon diagnoses should return this encounter . The free text entries were automatically coded using the Mayo Vocabulary Processor . Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM and using these entry points , a retrieval set was generated from the underlying corpus of records . Each retrieval set was compared with the Gold St and ard created by the expert indexers . RESULTS SNOMED-RT produced significantly greater specificity in its retrieval sets ( 99.8 % vs. 98.3 % , p<0.001 McNemar Test ) . The positive likelihood ratios were significantly better for SNOMED-RT retrieval sets ( 264.9 vs. 33.8 , p<0.001 McNemar Test ) . The positive predictive value of a SNOMED-RT retrieval was also significantly better than ICD9-CM ( 92.9 % vs. 62.4 % , p<0.001 McNemar Test ) . The accuracy defined as 1 ( the total error rate ( FP+FN ) / Total # episodes queried ( 20,220 ) ) was significantly greater for SNOMED-RT ( 98.2 % vs. 96.8 % , p=0.002 McNemar Test ) . Interestingly , the sensitivity of the SNOMED-RT generated retrieval set was not significantly different from ICD9-CM , but there was a trend toward significance ( 60.4 % vs. 57.6 % , p=0.067 McNemar Test ) . However , if we examine only the outpatient practice SNOMED-RT produced a more sensitive retrieval set than ICD9-CM ( 54.8 % vs. 46.4 % , p=0.002 McNemar Test ) . CONCLUSIONS Our data clearly shows that information regarding both common and rare disorders is more accurately identified with automated SNOMED-RT indexing using the Mayo Vocabulary Processor than it is with traditional h and picked constellations of codes using ICD9-CM . SNOMED-RT provided more sensitive retrievals of outpatient episodes of care than ICD9-CM The accuracy of the discharge diagnoses recorded in hospital medical records , and the accuracy of their ICD codes , were retrospectively examined in 174 r and omly chosen hospital patients . There was a 29 % error rate in the recorded ICD codes when compared at a three digit level to the results obtained by retrospectively review ing the records , establishing diagnoses and coding them . The error rate increased when medical records coders , rather than medically trained personnel , undertook the task of establishing the discharge diagnoses How well can hospital discharge abstract s be used to estimate patient health status ? This paper compares information on comorbidity obtained from hospital discharge abstract s for patients undergoing prostatectomy or cholecystectomy at a Winnipeg teaching hospital with clinical data on preoperative medical conditions prospect ively collected during an Anesthesia Follow-up study . The diagnostic information on cardiovascular disease , respiratory disease , and metabolic disorders showed considerable agreement , ranging from 65 to over 90 % correspondence across the two data sets . Certain conditions noted by the anesthesiologist were often absent from the cl aims data ; cardiovascular disease was recorded in the clinical data but absent from the cl aims for 31 % of prostatectomy and 17 % of cholecystectomy cases . Such patients were less likely to have been assigned a high score on the ASA Physical Status measure or to have high-risk diagnoses on the hospital file . Similar findings result ed from comparing the two sources in their ability to predict such adverse outcomes as mortality and readmission to hospital : the anesthesia file generally included less serious comorbidity AIMS To investigate the accuracy of admission and discharge coding of traumatic brain injury ( TBI ) in a New Zeal and hospital . METHOD Prospect i ve study of all patients over fifteen years of age admitted to Hutt Hospital over a six-month period with an actual or potential diagnosis suggesting TBI . RESULTS During the six month period of study , 65 patients with the diagnosis of TBI were admitted to Hutt Hospital . Of these , 21 ( 32.3 % ) met the criteria for diagnosis of TBI ( ' Definite TBI ' ) . A further eighteen patients , not admitted with a diagnosis of TBI , met the TBI criteria . Only 14/39 ( 35.9 % ) of ' Definite TBI ' cases were identified at both admission and discharge . Discharge diagnosis of TBI identified correctly 26/39 ( 66.7 % ) of definite cases , with 34/60 ( 56.7 % ) cases with a discharge diagnosis of TBI not meeting our criteria for the diagnosis of TBI . Six out of 39 ' Definite TBI ' cases ( 15.4 % ) were not identified by either admission or discharge diagnosis . Thirty of the 65 patients ( 46.2 % ) admitted to hospital with the diagnosis of TBI showed clinical evidence of having taken alcohol , although only 12 had blood alcohol concentration measured . CONCLUSIONS The admission and discharge diagnoses of TBI were not accurate when compared to a st and ard definition of TBI . For hospital discharge data to have any value , agreement on an operational diagnosis of TBI needs to be made , which should include measurement of the blood alcohol concentration . A suggestion for a diagnostic strategy is presented , along with ICD-10-AM codes that could be used to improve the current situation As an initial phase of the Endophthalmitis Population Study of Western Australia ( EPSWA ) , this paper reports the results from an intensive comparative validation of all possible surgery-related endophthalmitis cases identified for the period from 1980 to June 1999 from the Hospital Morbidity Data System ( HMDS ) of the WA Record Linkage Project with external sources . The external sources were the microbiology and anaesthetic data bases from Royal Perth Hospital ( where most of the cases of endophthalmitis were treated ) and surgeon logbooks of two vitreoretinal surgeons treating endophthalmitis in Perth over the study period . As it was discovered that a large proportion of all cases coded with endophthalmitis did not have any ocular surgery , the validation also included a sample from these cases . The purpose of validating these cases was to ensure that our count of postoperative endophthalmitis had not excluded any cases whose surgery might not have been recorded in the HMDS data base . It was also intended to provide an estimate of all miscoded endophthalmitis cases as a first step towards future improvement of coding accuracy . Since we suspected that phaco-emulsification was under-coded , we also examined a sample of cataract procedures . Of all surgery-related endophthalmitis cases coded in the HMDS , only 50.9 % ( 274 of 538 ) were found to be valid cases . External sources identified 83 cases of endophthalmitis , 49 did not have endophthalmitis codes but were in the HMDS file with an associated code . Of the remaining externally identified cases , 13 were missing altogether from the HMDS file , 7 of which were correctly coded in the notes while the other 6 were coded with associated codes , and 21 were diagnosed after the date the HMDS file was extracted . The validation of a r and om sample of the non-surgery-related cases coded with endophthalmitis suggested that the vast majority of them were miscoded ( 88 % , 139 of 158 sample d from 1474 cases ) . The systematic coding errors reported in this paper may be attributed to both the clinical and the coding departments of the hospital . In any case , coding inaccuracy itself is a serious concern for data quality of any linked data base systems and for epidemiological research ers using such data . The increased use of aggregated data in epidemiological research further underscores the importance of coding accuracy and thus data validation . The use of external sources for case identification and case validation are two ways of ensuring data completeness/ quality and validity of results The purpose of this study is to assess whether postoperative complications can be ascertained using administrative data . We r and omly sample d 991 adults who underwent elective open diskectomies at 30 nonfederal acute care hospitals in California . Postoperative complications were specified by review ing medical literature and by consulting clinical experts . We compared hospital-reported ICD-9-CM data and independently recoded ICD-9-CM data with complications abstract ed by clinicians using detailed criteria . Recoded ICD-9-CM data were more likely than hospital-reported ICD-9-CM data to capture true complications , when they occurred , but they also mislabeled more patients who never experienced clinical ly significant complications . This finding was most evident for mild or ambiguous complications , such as atelectasis , posthemorrhagic anemia , and hypotension . Overall , recoded ICD-9-CM data captured 47 % and 56 % of all mild and severe complications , respectively , whereas hospital reported ICD-9-CM data captured only 37 % and 44 % , respectively , of all mild and severe complications . These findings raise questions about the validity of using administrative data to ascertain postoperative complications , even if coders are carefully hired , trained , and supervised . ICD-9-CM complication codes are more promising as a tool to help providers identify their own adverse outcomes than as a tool for comparing performance OBJECTIVE To determine the accuracy of diagnoses and procedure codes in medical records for hip fracture patients . DESIGN A validation sample of hip fracture medical records was used to compare the facesheet data with progress notes , operative reports , and discharge summaries for patients in a prospect i ve study of functional recovery . SETTING Eight Baltimore hospitals with the highest volume of older hip fracture patients . PATIENTS Study subjects were 343 community-dwelling patients , 65 years of age and older , admitted to one of eight Baltimore hospitals between January 1990 and June 1991 with a diagnosis of hip fracture . MAIN OUTCOME MEASURES Facesheet diagnosis codes were compared with admitting notes , discharge summary , and /or progress notes . The abstract ed surgical procedure was compared with postoperative radiographs . RESULTS Excess coding of diagnoses on the hospital facesheet was evident in 12 % of charts . In 17 % of charts , a complication identified in the chart was not coded on the facesheet . More complications with low severity were omitted . Agreement between the abstract or 's procedure review and radiograph readings for arthroplasty was 84 % . In 15 % of patients , the abstract or coded total arthroplasty when hemiarthroplasty was done . CONCLUSIONS Discrepancy between the hospital facesheet and the medical record and between the abstract ed surgical procedure and radiographs was found for hip fracture patients . This may make findings from health outcomes research relying on administrative data bases uncertain and reimbursement inaccurate Background . Several quality assessment systems use administrative data to identify postoperative complications , with uncertain validity . Objectives . To determine how accurately postoperative complications are reported in administrative data , whether accuracy varies systematic ally across hospitals , and whether serious complications are more consistently reported . Design . Retrospective cohort . Subjects . Nine hundred ninety-one r and omly sample d adults who underwent elective lumbar diskectomies at 30 nonfederal acute care hospitals in California in 1990 to 1991 . Hospitals with especially low or high risk-adjusted complication rates , and patients who experienced complications , were over sample d. Measures . Postoperative complications were specified by review ing medical literature and consulting clinical experts ; each complication was mapped to ICD-9-CM . Hospital-reported complications were compared with our independent recoding of the same records . Results . The weighted sensitivity , specificity , and positive and negative predictive values for reported complications were 35 % , 98 % , 82 % , and 84 % , respectively . The weighted sensitivity was 30 % for serious , 40 % for minor , and 10 % for question able complications . It varied from 21 % among hospitals with fewer complications than expected to 45 % among hospitals with more complications than expected . Only reoperation , bacteremia/sepsis , postoperative infection , and deep vein thrombosis were reported with at least 60 % sensitivity . Half of the difference in risk-adjusted complication rates between low and high outlier hospitals was attributable to reporting variation . Conclusions . ICD-9-CM complications were underreported among diskectomy patients , especially at hospitals with low risk-adjusted complication rates . The validity of using coded complications to compare provider performance is question able , even with careful efforts to identify serious events , although these results must be confirmed using more recent data While the impact of maternal morbidities and intrapartum procedures is a common topic in perinatal outcomes research , the accuracy of the reporting of these variables in the large administrative data bases ( birth certificates , hospital discharges ) often utilised for such research is largely unknown . We conducted this study to compare maternal diagnoses and procedures listed on birth certificates , hospital discharge data , and birth certificate and hospital discharge data combined , with those documented in a stratified r and om sample of hospital medical records of 4541 women delivering liveborn infants in Washington State in 2000 . We found that birth certificate and hospital discharge data combined had substantially higher true positive fractions ( TPF , proportion of women with a positive medical record assessment who were positive using the administrative data bases ) than did birth certificate data alone for labour induction ( 86 % vs. 52 % ) , cephalopelvic disproportion ( 83 % vs. 35 % ) , abruptio placentae ( 85 % vs. 68 % ) , and forceps-assisted delivery ( 89 % vs. 55 % ) . For procedures available only in hospital discharge data , TPFs were generally high : episiotomy ( 85 % ) and third and fourth degree vaginal lacerations ( 91 % ) . Except for repeat caesarean section without labour ( TPF , 81 % ) , delivery procedures available only in birth certificate data had low TPFs , including augmentation ( 34 % ) , repeat caesarean section with labour ( 61 % ) , and vaginal birth after caesarean section ( 62 % ) . Our data suggest that research ers conducting perinatal epidemiological studies should not rely solely on birth certificate data to detect maternal diagnoses and intrapartum procedures accurately OBJECTIVE To assess the accuracy of information in an administrative data base ( Canadian Institute for Health Information ; CIHI ) compared with the hospital record for patients undergoing knee replacement ( KR ) . METHODS A stratified r and om sample of 185 KR recipients from 5 Ontario hospitals were chosen . Their hospital records and corresponding CIHI files were compared to assess percent complete agreement , false negative ( FN ) and false positive ( FP ) rates for demographic data , procedures , and diagnoses . RESULTS Of 185 records , 175 ( 95 % ) were review ed . Percent complete agreement was greater than 94 % for each of patient demographics and procedures ( mean FN rates : 0 % ; mean FP rates : 0 - 5 % ) . For comorbidities and complications , although mean percent complete agreement was high , and FP rates were low , mean FN rates were 63 % for specific comorbid conditions and 70 % for organ systems . CONCLUSIONS High FN rates have been found in documentation of comorbidities and in-hospital complications for CIHI data compared with the hospital record . Under-coding of comorbidities and in-hospital complications has potential implication s for research ers using administrative data bases OBJECTIVES This study examined the reliability of Department of Veterans Affairs ' health information data bases concerning patient demographics , use of care , and diagnoses . METHODS The Department of Veterans Affairs ' Patient Treatment files for Main , Bed-section ( PTF ) and Outpatient Care ( OCF ) were compared with medical charts and administrative records ( MR ) for a r and om national sample of 1,356 outpatient visits and 414 inpatient discharges to Department of Veterans Affairs ' facilities between July 1 and September 30 , 1995 . Records were uniformly abstract ed by a focus group of utilization review nurses and medical record coders blinded to administrative file entries . RESULTS Reliability was adequate for demographics ( kappa approximately 0.92 ) , length of stay ( agreement=98 % ) , and selected diagnoses ( kappa ranged 0.39 to 1.0 ) . Reliability was generally inadequate to identify the treating bedsection or clinic ( kappa approximately 0.5 ) . Compared with medical charts , Patient Treatment Files/Outpatient Care Files reported an additional diagnosis per discharge and 0.8 clinic stops per outpatient visit , result ing in higher estimates of disease prevalence ( + 39 % heart disease , + 19 % diabetes ) and outpatient costs ( + 36 % per unique outpatient per quarter ) . CONCLUSIONS In the absence of pilot work validating key data elements , investigators are advised to construct health and utilization data from multiple sources . Further validation studies of administrative files should focus on the relation between process of data capture and data validity Insurance cl aims data are being used increasingly to study clinical outcomes and quality of care [ 1 - 4 ] . Each year , hospital-specific mortality rates , adjusted by clinical ly modified International Classification of Diseases ( ICD-9-CM ) codes from Medicare bills , are released by the Health Care Financing Administration ( HCFA ) [ 1 - 3 ] . Using ICD-9-CM data to adjust for illness severity , threefold differences for surgeon-specific mortality in Philadelphia were found by Williams and colleagues [ 4 ] . Many of the Patient Outcomes Research Teams ( PORTs ) , supported by the Agency for Health Care Policy Research , are using ICD-9-CM coded Medicare discharge abstract s to examine the process of medical care , including physician- and hospital-specific performance [ 5 - 7 ] . The potential advantages of using insurance cl aims data sets for clinical research have been described in many previous publications [ 8 ] . They include 1 ) large sample s of geographically dispersed patients ; 2 ) longitudinal records ; 3 ) data already collected and available ; and 4 ) defined sampling frames . The question remains : Are data collected to obtain insurance reimbursement a valid proxy for data collected for clinical care and research purpose s ? Such validity is essential to identify clinical ly relevant population s and to adjust for illness severity and differences in outcomes [ 9 ] . Six re abstract ing studies have attempted to answer this question with respect to analysis of patients discharged after acute myocardial infa rct ion [ 10 - 15 ] . These studies selected patients with the ICD-9-CM code 410 , the code for acute myocardial infa rct ion . By examining medical records , they found that clinical criteria for an acute myocardial infa rct ion were met in 43 % to 87 % of records where the code was used at discharge . Errors result ed when the physician listed the acute myocardial infa rct ion incorrectly , when a myocardial infa rct ion occurred in a previous admission , or when myocardial infa rct ion was ruled out ( if it was the admitting diagnosis ) . A substantial limitation of five of these studies was that they selected patients based on cl aims data . Thus , the groups selected for review were only those patients with an ICD-9-CM code for myocardial infa rct ion . Using this design , it was only possible to obtain estimates of disagreement in one direction ; patients who had a condition coded in the clinical data set , but not in the cl aims data set , could not be examined . A second limitation of the previous studies is that their comparison gold st and ard was based on retrospective review of information recorded in the discharge summary or medical chart . Medical record data are limited by the unstructured way in which they are collected . Inaccuracies in these sources can not be identified in such a study , and it is possible that in some disagreements with ICD-9-CM codes , the medical record is incorrect . Our study examined the suitability of billing data compared with clinical data ( prospect ively collected for cardiology research and patient care ) for use in clinical outcomes research . The descriptors for coronary artery disease that we examined were those listed as important determinants of prognosis by an expert panel from the American College of Cardiology [ 16 ] . Methods Insurance Cl aims Data The administrative or insurance cl aims information comprised all discharge abstract s from Duke University Medical Center between July 1985 and May 1990 containing any procedure code for coronary arteriography . All discharged patients , regardless of insurance status or age , were routinely classified by ICD-9-CM codes recorded by trained medical record technicians based on the attending physician 's listed discharge diagnoses , the discharge summary , and selected information from the progress notes and from the test result sections of the hospital chart [ 17 ] . These records contained up to 30 diagnostic codes and 9 procedure codes . After the technician had assembled the ICD-9-CM codes , the discharge abstract and the chart were returned to the attending physician for final approval by signature ; ICD-9-CM codes were not generated for patients having outpatient cardiac catheterization unless they were subsequently admitted for further evaluation or treatment . The records for the subgroup of Medicare patients in this study were sent by Duke Hospital to the North Carolina Medicare intermediary and , thus , reflect the Duke Hospital data contained in the Health Care Financing Administration data sets . Clinical Data base Data The clinical information consisted of important diagnostic and prognostic information about coronary artery disease routinely collected on st and ardized data forms by the cardiology fellow doing the cardiac catheterization for suspected ischemic heart disease . Information collected included details from the patient history , physical examination , laboratory studies , and cardiac catheterization , as previously described [ 18 ] . Each new fellow entering the catheterization laboratory was given a 3-hour training session on variable definitions and use of the data forms and was given an operations manual covering these details . In addition , all data were review ed for accuracy by the attending angiographer associated with the case ; additional consistency , range check , and other quality control measures were done during the data entry process by trained research technicians . This information was stored in the Duke Data bank for Cardiovascular Disease , a completely separate and independent system from the hospital administrative records described above . Records Matching and Variable Definitions Records from the administrative and clinical files were matched by unique , patient hospital identification numbers and hospitalization date s. Only the first matching clinical record for each patient was included in the analysis . Twelve clinical variables were mapped to ICD-9-CM codes according to an algorithm developed by the Patient Outcomes Research Team for chronic ischemic heart disease ( Table 1 ) ( Romano PS , Roos LL . Unpublished observations ) . The variables studied were selected if they met two criteria : 1 ) They were considered to be determinants of prognosis for coronary artery disease according to an expert panel from the American College of Cardiology ; 2 ) they could be mapped to diagnoses contained in the ICD-9-CM coding system [ 16 , 17 ] . The definitions of the clinical ly identified conditions appear in the Appendix . Table 1 . International Classification of Diseases-9-CM and Clinical Detail Map Appendix . Glossary of Terms Data Analysis Based on the clinical condition and the ICD-9-CM map described above , two-by-two tables were constructed to assess the agreement between the data sources . For the cl aims data , a condition was considered to be absent if it was not coded . For the clinical data , patients with missing data were excluded from the analysis for the specific missing condition . Kappa statistics were generated for each condition to measure agreement while controlling for chance agreement [ 19 ] . Confidence intervals and test statistics for proportions were calculated by the normal approximation . For the diagnoses of acute myocardial infa rct ion , congestive heart failure , angina , and unstable angina , we review ed a r and om sample of 15 clinical -positive and cl aims -negative charts as well as 15 cl aims -positive and clinical -negative charts for each diagnosis to illustrate the major reasons for disagreement . In addition to the comparisons made in the overall data sets , subsets defined by age , fiscal year , and sex were compared to determine if the coding accuracy varied according to these factors . Results The study group consisted of 12 937 consecutive patients having inpatient cardiac catheterization between July 1985 and May 1990 . Although each record represented the first cardiac catheterization in the cl aims records , from the perspective of the clinical records , 89 % involved the first catheterization , 8 % involved the second catheterization , and the remaining 3 % involved the third or subsequent catheterization . The patients had a mean age of 58.8 years , 34 % were women , and the racial composition was 88 % white , 10 % black , and 2 % other . At cardiac catheterization , the mean left ventricular ejection fraction was 52 % . The distribution of the number of diseased major epicardial vessels ( zero , one , two , or three ) was 23 % , 26 % , 23 % , and 28 % , respectively . Overall , the study group characteristics were similar to those of other large angiographic registries except for the greater proportion of women and the higher mean age [ 20 , 21 ] . Measures of Agreement Specific measures of agreement between clinical data base and ICD-9-CM variables are listed in Table 2 in descending order of value ( the agreement rate adjusted for chance agreement ) . Kappas ranged from 0.83 for diabetes mellitus to 0.09 for unstable angina . Of the 12 conditions , only 3 ( diabetes , acute myocardial infa rct ion , and hypertension ) were identified by the cl aims data more than 50 % of the time that they were identified by the clinical data . Table 2 . Comparison of Agreement by Condition Ranked by Kappa Value In the clinical data set , two conditions were grade d according to severity , congestive heart failure , and mitral regurgitation . With increasing severity levels , the cl aims data were more likely to identify the presence of these conditions . Cl aims data identified 31 % of clinical ly identified congestive heart failure that was New York Heart Association class I and II and identified 45 % of class III and IV heart failure ( P < 0.0001 ) [ 22 ] . Similarly , cl aims data identified 40 % of grade s I and II mitral regurgitation and identified 69 % of grade s III and IV mitral regurgitation ( P < 0.0001 ) . When all diagnoses were considered together , the overall agreement of ICD-9-CM codes with clinical data was 0.75 ( 99 % CI , 0.75 to 0.76 ) . The proportion of conditions in the clinical data set identified by cl aims data was 0.39 ( 99 % CI , 0.38 to 0.39 ) ( Table 3 ) . Stratified by The quality of medical records data for patients who were hospitalized with community-acquired pneumonia was assessed by comparing medical records data with data obtained in a prospect i ve study of pneumonia for the period April 1 , 1984 , to December 31 , 1984 . One hundred five patients fulfilled the case definition of pneumonia for entry into the prospect i ve study . One hundred twenty-seven patients were identified by medical records data . Seventy-three of the patients appeared in both studies . The positive predictive accuracy of the medical records data was 57 % . When the etiologic diagnoses for the 73 patients identified by both studies were compared , there was agreement only 52.6 % of the time . Streptococcus pneumoniae was overdiagnosed , and Mycoplasma , specific viral causes , and Haemophilus influenzae were not recorded by the medical records data . The quality of medical records data regarding pneumonia can be improved by changing the current ICD-9-CM coding system for pneumonia and by providing instruction and an algorithm for abstract ors to follow in assigning a diagnosis of pneumonia OBJECTIVE The goal of this study was to assess the validity of the International Classification of Disease , 10th Version ( ICD-10 ) administrative hospital discharge data and to determine whether there were improvements in the validity of coding for clinical conditions compared with ICD-9 Clinical Modification ( ICD-9-CM ) data . METHODS We review ed 4,008 r and omly selected charts for patients admitted from January 1 to June 30 , 2003 at four teaching hospitals in Alberta , Canada to determine the presence or absence of 32 clinical conditions and to assess the agreement between ICD-10 data and chart data . We then re-coded the same charts using ICD-9-CM and determined the agreement between the ICD-9-CM data and chart data for recording those same conditions . The accuracy of ICD-10 data relative to chart data was compared with the accuracy of ICD-9-CM data relative to chart data . RESULTS Sensitivity values ranged from 9.3 to 83.1 percent for ICD-9-CM and from 12.7 to 80.8 percent for ICD-10 data . Positive predictive values ranged from 23.1 to 100 percent for ICD-9-CM and from 32.0 to 100 percent for ICD-10 data . Specificity and negative predictive values were consistently high for both ICD-9-CM and ICD-10 data bases . Of the 32 conditions assessed , ICD-10 data had significantly higher sensitivity for one condition and lower sensitivity for seven conditions relative to ICD-9-CM data . The two data bases had similar sensitivity values for the remaining 24 conditions . CONCLUSIONS The validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions was generally similar though validity differed between coding versions for some conditions . The implementation of ICD-10 coding has not significantly improved the quality of administrative data relative to ICD-9-CM . Future assessment s like this one are needed because the validity of ICD-10 data may get better as coders gain experience with the new coding system The aim of this study was to assess the data quality of postoperative infections in a hospital discharge registry in the Emilia-Romagna region of Italy . Data from a prospect i ve regional study of postoperative infections in 6158 patients from 31 of the 36 public hospitals of the region were compared with data from the regional hospital discharge registry , using different classes of ICD-9-CM codes . The sensitivity of the hospital discharge data base for postoperative surgical infections was 10 % when ICD-9-CM codes directly indicative of postoperative infectious complications were used . When non-specific codes of postoperative complications , not necessarily of infectious origin , were added , the sensitivity reached 21 % . At present , the hospital discharge registry is not suited for surveillance of hospital-acquired infection BACKGROUND The Department of Veterans Affairs ( DVA ) National Surgical Quality Improvement Program ( NSQIP ) employs trained nurse data collectors to prospect ively gather preoperative patient characteristics and 30-day postoperative outcomes for most major operations in 123 DVA hospitals to provide risk-adjusted outcomes to centers as quality indicators . It has been suggested that routine hospital discharge abstract s contain the same information and would provide accurate and complete data at much lower cost . STUDY DESIGN With preoperative risks and 30-day outcomes recorded by trained data collectors as criteria st and ards , ICD-9-CM hospital discharge diagnosis codes in the Patient Treatment File ( PTF ) were tested for sensitivity and positive predictive value . ICD-9-CM codes for 61 preoperative patient characteristics and 21 postoperative adverse events were identified . RESULTS Moderately good ICD-9-CM matches of descriptions were found for 37 NSQIP preoperative patient characteristics ( 61 % ) ; good data were available from other automated sources for another 15 ( 25 % ) . ICD-9-CM coding was available for only 13 ( 45 % ) of the top 29 predictor variables . In only three ( 23 % ) was sensitivity and in only four ( 31 % ) was positive predictive value greater than 0.500 . There were ICD-9-CM matches for all 21 NSQIP postoperative adverse events ; multiple matches were appropriate for most . Postoperative occurrence was implied in only 41 % ; same breadth of clinical description in only 23 % . In only four ( 7 % ) was sensitivity and only two ( 4 % ) was positive predictive value greater than 0.500 . CONCLUSION Sensitivity and positive predictive value of administrative data in comparison to NSQIP data were poor . We can not recommend substitution of administrative data for NSQIP data methods OBJECTIVES To compare the correspondence of discharges and diagnoses between medical records and an administrative data base in diabetic patients with foot ulcers and to calculate inpatient costs from the different sources . DESIGN Discharge data from 117 prospect ively followed patients were compared with information from the Swedish Inpatient Registry during the same treatment period for each patient . Non corresponding discharges were retrospectively review ed in patient records . Costs of inpatient care were calculated from clinical sources and from data selected in three different ways from the data base . Information in medical records was assumed to represent the ' Gold St and ard ' . SETTING In-hospital treatment , multidisciplinary foot-care team . SUBJECTS A total of 117 diabetic patients with deep foot infections . MAIN OUTCOME MEASURES Degree of data base completeness and inpatient costs . RESULTS The degree of completeness of discharges in the data base was 98 % , but 8.6 % of discharges had no code for diabetes and 13 % were registered without any foot related diagnosis code . Less than 20 % of discharges were found with selection based on primary diagnosis 250.G only . Total inpatient costs varied from 2.7 to 13.3 million SEK ( Swedish Kronor ) depending on selected diagnosis codes . Approximately 84 % of all foot ulcer discharges could be found in the data base if codes with both diabetes mellitus and foot ulcer diagnoses were selected . CONCLUSIONS Inpatient costs for foot complications can not be accurately estimated from the Inpatient Registry when based on primary diagnosis exclusively . Fairly good estimates at a low data acquisition cost can be made with a combination of foot related diagnoses together with codes for diabetes OBJECTIVE The purpose of this study was to determine the accuracy of live-birth certificates and hospital discharge data that reported of pre-existing maternal medical conditions and complications of pregnancy . STUDY DESIGN We conducted a population -based validation study in 19 non-federal short-stay hospitals in Washington state with a stratified r and om sample of 4541 women who had live births between January 1 , 2000 , and December 31 , 2000 . True- and false-positive fractions were calculated . RESULTS Birth certificate and hospital discharge data combined had substantially higher true-positive fractions than did birth certificate data alone for cardiac disease ( 54 % vs 29 % ) , acute or chronic lung disease ( 24 % vs 10 % ) , gestational diabetes mellitus ( 93 % vs 64 % ) , established diabetes mellitus ( 97 % vs 52 % ) , active genital herpes ( 77 % vs 38 % ) , chronic hypertension ( 70 % vs 47 % ) , pregnancy-induced hypertension ( 74 % vs 49 % ) , renal disease ( 13 % vs 2 % ) , and placenta previa ( 70 % vs 33 % ) . For the 2 medical risk factors that are available only on birth certificates , true-positive fractions were 37 % for established genital herpes and 68 % for being seropositive for hepatitis B surface antigen . CONCLUSION In Washington , most medical conditions and complications of pregnancy that affect mothers are substantially underreported on birth certificates , but hospital discharge data are accurate in the reporting of gestational and established diabetes mellitus and placenta previa . Together , birth certificate and hospital discharge data are much superior to birth certificates alone in the reporting of gestational diabetes mellitus , active genital herpes , and chronic hypertension OBJECTIVE Diagnostic data are essential for the assessment of medical practice : they are needed for retrieval of clinical cases and describing co-morbidity and complications . In most Western countries , diagnosis registration in hospital information systems is based mainly on completing forms after patient discharge . As this registration plays no role in patient care , data quality is usually unsatisfactory . To improve data quality , we re design ed the process of diagnosis registration at a paediatric department , and now paediatricians provide diagnoses with codes in a separate registration heading of the discharge letter . We compared the quality of this discharge letter-linked diagnosis registration with the quality of the previous form based registration . DESIGN Retrospective study with blinded before and after measurement . Re- abstract ed diagnosis descriptions of the text of discharge letters were taken as gold st and ard . SETTING A paediatric department in an academic medical centre . STUDY PARTICIPANTS From each registration period , 60 admissions were selected r and omly . Mean age of the patients was 4.5 ( SD + /- 5.5 ) and 5.2 ( SD + /- 5.2 ) years for the old and new situation respectively . Mean length of stay was 8.8 ( SD + /- 11.0 ) and 7.2 ( SD + /- 12.4 ) days . INTERVENTION Discharge letter-linked diagnosis registration . MAIN OUTCOME MEASURES Completeness and accuracy , both at three-digit level of ICD-9-CM . RESULTS Completeness of form-based diagnosis registration was 51 % ( 95 % CI , 44 - 58 % ) and of discharge letter-linked diagnosis registration 54 % ( 95 % CI , 47 - 60 % ) . Accuracy was 65 % ( 95 % CI , 58 - 72 % ) and 67 % ( 95 % CI , 60 - 74 % ) respectively . CONCLUSIONS The discharge letter-linked diagnosis registration does not provide a better basis for assessment of medical practice than the form based diagnosis registration conjugate vaccines induce T cell dependency and thereby prime for a secondary immune response , immunised infants may be protected against H influenzae type b irrespective of the concentration of circulating antibodies . In our study five infants had natural rises in their antibody concentrations in the absence of clinical disease . These and other results 4 suggest that infants are primed by immunisation for a mature for age response to either the organism or cross reactive antigen . In an open controlled prospect i ve trial in the Oxford region we have shown the vaccine to be highly protective . ' Nationwide postmarketing surveillance ( in collaboration with the British Paediatric Surveillance Unit ) is examining the long term efficacy of the conjugate vaccine given to children at 2 , 3 , and 4 months without a booster dose in their second year . We thank Dr R T Mayon-White and Dr J A Macfarlane for their helpful comments on both the study 's design and the manuscript , Dr J S Kroll for editorial advice , the families who agreed to participate in the study , and Mrs Carole Barr for typing the manuscript . Haemophilus influenzae type b disease in Wales . Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule . Rees DG , et al. Haemophilus influenaze type b conjugate vaccine trial in Oxford : implication s for the UK . et al. Safety and immunologic response to Haemophilus influenzae type b oligosaccharide-CRM 197 conjugate vaccine in 1-to-6 month old infants . of Haemophilus influenzae type B conjugate vaccine in Oxford region . To allow de central isation of coding the Central Middlesex Hospital NHS Trust has purchased a hospital wide information technology system . We conducted a study to evaluate completeness and accuracy of clinical coding in the paediatric department before and after its installation . Material s and methods , and results Medical records of children admitted to the paediatric ward between 1 September and 31 October 1990 and 1991 were review ed , respectively six months before and six months after coding was de central ised and responsibility transferred to medical staff . Diagnoses independent of that registered in hospital records were allocated by CY for 1990 and HD for 1991 . Twenty from each year were checked by both of us ; in these cases attributed codes agreed . Diagnoses were then compared with those allocated by coding clerks ( 1990 ) or those entered by medical staff on the computer ( 1991 ) BACKGROUND The aim of the study was to assess the reproducibility of clinical coding in two National Health Service hospitals within North West Thames region . METHODS A retrospective audit was carried out , of clinical coding in hospital episode statistics , involving comparison of the codes assigned by local staff with those assigned by members of an external team unaware of the locally assigned codes . Where local and external coders disagreed , the records were review ed for a third time by a further independent coder . The subjects were a r and om sample of 1607 non-maternity , non-psychiatric admissions occurring between 1991 and 1993 , stratified for year and type of disease ( asthma , diabetes , appendicitis , fractured femur and ' general'--a r and om selection of any diagnoses ) . The main outcome measures were the levels of exact agreement between local and external teams over codes for main diagnosis and procedure , and the level of approximate agreement ( over the first three characters of the ICD-9 code for diagnosis and the letter and first two digits of the OPCS-4 code for procedure ) . For disagreements , the outcome measure was the level of agreement between the ' third ' coder and the local and external coders . RESULTS For the main diagnosis in the ' general ' group at hospital A , internal and external coders agreed exactly in 43 per cent of the admissions examined and agreed ' approximately ' in 55 per cent ( kappa = 0.54 ) . For hospital B the corresponding figures were 60 per cent and 72 per cent ( kappa = 0.72 ) . Approximate agreement was higher for the specific diseases considered , particularly for asthma ( A : 86 per cent ; B : 91 per cent ) and fractured femur ( A : 84 per cent ; B : 89 per cent ) . For the main procedure at hospital A , there was exact agreement for 58 per cent and approximate agreement for 70 per cent ( kappa = 0.66 ) . For hospital B , the corresponding figures were 76 per cent and 83 per cent ( kappa = 0.80 ) . In cases of disagreement over the first three digits of the ICD-9 code for main diagnosis , the third coder disagreed with both local and external coders in 53 per cent at hospital A and 38 per cent at hospital B. Agreement was slightly better for discharges in 1992 - 1993 than in 1991 - 1992 . CONCLUSIONS The full clinical codes in NHS hospital episode statistics ( HES ) data should be treated with caution . The first three characters of ICD-9 codes for diagnoses and the OPCS-4 codes for procedures were more reliable . For some specific conditions such as asthma and fractured femur , reliability of the first three characters is much higher ( for example , 86 per cent and 91 per cent for asthma in the two hospitals ) , but for the full codes can be worse . Secondary diagnoses or comorbidities may be significantly undercoded . A higher level of agreement in 1992 - 1993 than in 1991 - 1992 suggests that coding may be improving The objective of this study was to assess whether administrative ( cl aims ) data bases can be used to assess clinical variables and predict outcome . Although administrative data bases are useful for assessing re source utilization , their utility for assessing clinical information is less certain . Prospect ively gathered clinical data bases , however , are expensive and not widely available . The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular data base at Emory University . The cl aims data base was compared with the clinical data base for 11 variables . Outcome models were developed with multivariate methods . A total of 11,883 patients who underwent catheterization ( 5,255 underwent percutaneous transluminal coronary angioplasty [ PTCA ] and 3,794 underwent coronary artery bypass surgery [ CABG ] ) between 1991 and 1995 were included . For some variables , the cl aims data base correlated well ( diabetes , sensitivity 87 % , specificity 99 % ) , whereas for others the cl aims data base was less accurate ( peripheral vascular disease , sensitivity 20 % , specificity 99 % ) . Uncertain coding in the cl aims data base , which can result in the same code being used for co-morbid states and severity of disease , as well as complications , limited the ability of cl aims to predict outcome . Clinical data bases may also be limited by lack of objectivity and missing data . The utility of cl aims data bases to assess severity of disease and co-morbid states is limited , and outcome modeling and risk assessment from cl aims data bases may be inappropriate and spurious . Developing better data st and ards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment |
11,206 | 21,824,385 | Conclusion The majority of CCDSSs demonstrated improvements in process of care , but patient outcomes were less likely to be evaluated and far less likely to show positive results | Background Acute medical care often dem and s timely , accurate decisions in complex situations .
Computerized clinical decision support systems ( CCDSSs ) have many features that could help .
However , as for any medical intervention , cl aims that CCDSSs improve care processes and patient outcomes need to be rigorously assessed .
The objective of this review was to systematic ally review the effects of CCDSSs on process of care and patient outcomes for acute medical care . | 200 adult respiratory distress syndrome patients were included in a prospect i ve multicenter r and omized trial to determine the efficacy of computerized decision support . The study was done in 10 medical centers across the United States . There was no significant difference in survival between the two treatment groups ( mean 2 = 0.49 p = 0.49 ) or in ICU length of stay between the two treatment groups when controlling for survival ( F(1df ) = 0.88 , p = 0.37 . ) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group ( F(1df ) = 4.1 , p = 0.04 ) as well as significantly lower incidence and severity of overdistension lung injury ( F(1df ) = 45.2 , p < 0.001 ) . We rejected the null hypothesis . Efficacy was best for the protocol group . Protocol s were used for 32,055 hours ( 15 staff person years , 3.7 patient years or 1335 patient days ) . Protocol s were active 96 % of the time . 38,546 instructions were generated . 94 % were followed . This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical setting s and significantly improve patient morbidity We developed a computer-stored medical record system containing a limited set of the total clinical data base -- primarily diagnostic studies and treatments . This system responds to its own content according to physician-authored reminder rules . To determine the effect of the reminder messages generated by 1490 rules on physician behavior , we r and omly assigned practitioners in a general medicine clinic to study or control groups . The computer found indications for six different actions per patient in 12 467 patients during a 2-year study : 61 study group residents who received computer reminders responded to 49 % of these indications ; 54 control group residents , to only 29 % ( p less than 0.0001 ) . Preventive care ( occult blood testing , mammographic screening , weight reduction diets , influenza and pneumococcal vaccines ) was affected . The intentions of the study group to use a given action for an indication predicted their response to the indications ( p less than 0.03 , r2 = 0.33 ) . The intentions of the control residents did not 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 OBJECTIVE To compare effects on premature infants ' weight gain of a computer-generated and a nurse-determined incubator humidity strategy . An optimal humidity protocol is thought to reduce time to regain birthweight . DESIGN Prospect i ve r and omized controlled design . SETTING Level IIIC neonatal intensive care unit in the Netherl and s. PARTICIPANTS Infants of 24 to 30 weeks gestational age with a birthweight less than 1,500 g. INTERVENTION Two incubator humidity strategies were studied : computer-generated and nurse-determined humidity . MAIN OUTCOME MEASURE Time needed to regain birthweight . RESULTS One hundred thirty six infants were enrolled : 65 were exposed to the computer-generated strategy and 71 to the nurse-determined strategy . Demographic characteristics were well balanced between groups , with birthweight 981 + /- 245 versus 991 + /- 213 g , mean gestational age 27.7 + /- 1.7 versus 27.7 + /- 1.6 weeks . Main outcome did not significantly differ between strategies : survival analysis showed an equal number of days needed to regain birthweight ( median 9 days , with 95 % CIs 8 - 10 and 7 - 11 for infants exposed to the computer-generated and nurse-determined humidity strategy , respectively ) . CONCLUSION Computer-generated strategy does not reduce the time needed to regain birthweight Guided dosing within a computerized provider order entry ( CPOE ) system is an effective method of individualizing therapy for patients . Physicians ' responses to guided dosing decision support have not been extensively studied . As part of a r and omized trial evaluating efficacy of dosing advice on reducing falls in the elderly , CPOE prompts to physicians for 88 drugs included tailored messages and guided dose lists with recommended initial doses and frequencies . The study captured all prescribing activity electronically . The primary outcome was the ratio between prescribed dose and recommended dose . Over 9 months , 778 providers entered 9111 study -related medication orders on 2981 patients . Physicians using guided orders chose recommended doses more often than controls(28.6 % vs. 24.1 % , p<0.001 ) . Selected doses were significantly lower in the intervention group ( median ratio of actual to recommended 2.5 , interquartile range [ 1.0,4.0 ] ) than the control group ( median 3.0 interquartile range [ 1.5,5.0 ] , p<0.001 ) . While physicians selected the recommended dose less than a third of the time , guided geriatric dosing modestly improved compliance with guidelines Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice 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 OBJECTIVE To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations . DESIGN R and omized , controlled , evaluator-blinded trial . SETTING University-affiliated hospital . PATIENTS Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin , unless they were receiving therapeutic antibiotics at the time of surgery . INTERVENTION R and omization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics ( reminder group , n = 137 ) or control ( n = 136 ) . After another 30 minutes , the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered . RESULTS Intraoperative redosing was significantly more frequent in the reminder group ( 93 of 137 ; 68 % ) than in the control group ( 55 of 136 ; 40 % ) ( adjusted odds ratio , 3.31 ; 95 % confidence interval , 1.97 to 5.56 ; P < .0001 ) . The impact of the reminder was even greater when compared with the 6 months preceding the study period ( 129 of 480 ; 27 % ; P < .001 ) , suggesting some spillover effect on the control group . Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing . The rate of surgical-site infection in the reminder group ( 5 of 137 ; 4 % ) was similar to that in the control group ( 8 of 136 ; 6 % ; P = .42 ) , but significantly lower than that in the pre- study period ( 48 of 480 ; 10 % ; P = .02 ) . CONCLUSION The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis OBJECTIVES To evaluate the effectiveness of computer-assisted decision support in reducing potentially inappropriate prescribing to older adults . DESIGN R and omized , controlled trial . SETTING An academic emergency department ( ED ) in Indianapolis , Indiana , where computerized physician order entry was used to write all medication prescriptions . PARTICIPANTS Sixty-three emergency physicians were r and omized to the intervention ( 32 physicians ) or control ( 31 physicians ) group . INTERVENTION Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies . MEASUREMENTS The primary outcome was the proportion of ED visits by seniors that result ed in one or more prescriptions for an inappropriate medication . The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians ' reasons for rejecting the decision support . RESULTS The average age of the patients was 74 , two-thirds were female , and just over half were African American . Decision support was provided 114 times to intervention physicians , who accepted 49 ( 43 % ) of the recommendations . Intervention physicians prescribed one or more inappropriate medications during 2.6 % of ED visits by seniors , compared with 3.9 % of visits managed by control physicians ( P=.02 ; odds ratio=0.55 , 95 % confidence interval=0.34 - 0.89 ) . The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4 % to 3.4 % . The most common reason for rejecting decision support was that the patient had no prior problems with the medication . CONCLUSION Computerized physician order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors . This approach might be used in other efforts to improve ED care . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00297869 BACKGROUND Although they are effective in outpatient setting s , computerized reminders have not been proved to increase preventive care in inpatient setting s. METHODS We conducted a r and omized , controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for in patients . During an 18-month study period , a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service ( for a total of 10,065 hospitalizations ) , generating preventive care reminders as appropriate . Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for in patients . RESULTS The reminder system identified 3416 patients ( 53.6 percent ) as eligible for preventive measures that had not been ordered by the admitting physician . For patients with at least one indication , computerized reminders result ed in higher adjusted ordering rates for pneumococcal vaccination ( 35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group , P<0.001 ) , influenza vaccination ( 51.4 percent vs. 1.0 percent , P < 0.001 ) , prophylactic heparin ( 32.2 percent vs. 18.9 percent , P<0.001 ) , and prophylactic aspirin at discharge ( 36.4 percent vs. 27.6 percent , P<0.001 ) . CONCLUSIONS A majority of hospitalized patients in this study were eligible for preventive measures , and computerized reminders significantly increased the rate of delivery of such therapies Objectives : Having shown previously that an electronic prescription writer and decision support system improved pediatric prescribing behavior for otitis media in an academic clinic setting , we assessed whether point-of-care delivery of evidence could demonstrate similar effects for a wide range of other common pediatric conditions . Design : Cluster r and omized controlled trial . Setting : A teaching clinic/ clinical practice site and a primary care pediatric clinic serving a rural and semi-urban patient mix . Participants : A total of 36 providers at the teaching clinic/ practice site and eight providers at the private primary pediatric clinic . Intervention : An evidence -based message system that presented real-time evidence to providers based on prescribing practice s for acute otitis media , allergic rhinitis , sinusitis , constipation , pharyngitis , croup , urticaria , and bronchiolitis . Outcome measures : The proportion of prescriptions dispensed in accordance with evidence . Results : The proportion of prescriptions dispensed in accordance with evidence improved four percentage points , from 38 % at baseline to 42 % following the intervention . The control group improved by one percentage point , from 39 % at baseline to 40 % at trial 's conclusion . The adjusted difference between the intervention and control groups was 8 % ( 95 % confidence interval 1 % , 15 % ) . Intervention effectiveness did not decrease with time . Conclusion : For common pediatric outpatient conditions , a point-of-care evidence -based prescription writer and decision support system was associated with significant improvements in prescribing practice 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 OBJECTIVE To assess the effect of a computerized decision support system ( CDSS ) on the accuracy of patient temperature recording at the bed side . DESIGN This is a r and omized , controlled trial comparing nurses assigned to an intervention group that received CDSS whenever they attempted to store a low temperature ( < /= 96.4 degrees F ) or a control group that received no CDSS . MEASUREMENTS The computer recorded temperatures that would trigger reminders equally in both control and intervention groups . It also logged the reactions of nurses who received reminders and whether they retook the patient 's temperature or chose to store the original low value . RESULTS We analyzed the temperature data over a 10-month period tracking a total of 44339 temperatures taken by the control group and 45823 temperatures taken by the intervention group . We showed a 51 % relative reduction in the number of erroneous low temperatures stored by the intervention versus the control group . CONCLUSION CDSS are effective with nursing personnel in improving the accuracy of temperature capture at the bedside 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 BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment OBJECTIVE To assess compliance with a clinical decision support system ( CDSS ) for diagnostic management of children with fever without apparent source and to study the effects of application of the CDSS on time spent in the emergency department ( ED ) and number of laboratory tests . DESIGN The CDSS was used by ED nursing staff to register children presenting with fever . The CDSS identified children that met inclusion criteria ( 1 - 36 months and fever without apparent source ( FWS ) ) and provided patient-specific diagnostic management advice . Children at high risk for serious bacterial infection were r and omized for the ' intervention ' ( n = 74 ) or the ' control ' ( n = 90 ) group . In the intervention group , the CDSS provided the advice to immediately order laboratory tests and in the control group the ED physician first assessed the children and then decided on ordering laboratory tests . RESULTS Compliance with registration of febrile children was 50 % ( 683/1,399 ) . Adherence to the advice to order laboratory tests was 82 % ( 61/74 ) . Children in the intervention group had a median ( 25(th)-75(th ) percentile ) length of stay at the ED of 138 ( 104 - 181 ) minutes . The median length of stay at the ED in the control group was 123 ( 83 - 179 ) minutes . Laboratory tests were significantly more frequently ordered in the intervention group ( 82 % ) than in the control group ( 44 % , p < 0.001 , chi(2 ) test ) . CONCLUSION Implementation of a CDSS for diagnostic management of young children with fever without apparent source was successful regarding compliance and adherence to CDSS recommendations , but had unexpected effects on patient outcome in terms of ED length of stay and number of laboratory tests . The use of the current CDSS was discontinued OBJECTIVE To evaluate the effect of an automatic alerting system on the time until treatment is ordered for patients with critical laboratory results . DESIGN Prospect i ve r and omized controlled trial . INTERVENTION A computer system to detect critical conditions and automatically notify the responsible physician via the hospital 's paging system . PATIENTS Medical and surgical in patients at a large academic medical center . One two-month study period for each service . MAIN OUTCOMES Interval from when a critical result was available for review until an appropriate treatment was ordered . Secondary outcomes were the time until the critical condition resolved and the frequency of adverse events . METHODS The alerting system looked for 12 conditions involving laboratory results and medications . For intervention patients , the covering physician was automatically notified about the presence of the results . For control patients , no automatic notification was made . Chart review was performed to determine the outcomes . RESULTS After exclusions , 192 alerting situations ( 94 interventions , 98 controls ) were analyzed . The intervention group had a 38 percent shorter median time interval ( 1.0 hours vs. 1.6 hours , P = 0.003 ; mean , 4.1 vs. 4.6 hours , P = 0.003 ) until an appropriate treatment was ordered . The time until the alerting condition resolved was less in the intervention group ( median , 8.4 hours vs. 8.9 hours , P = 0.11 ; mean , 14.4 hours vs. 20.2 hours , P = 0.11 ) , although these results did not achieve statistical significance . The impact of the intervention was more pronounced for alerts that did not meet the laboratory 's critical reporting criteria . There was no significant difference between the two groups in the number of adverse events . CONCLUSION An automatic alerting system reduced the time until an appropriate treatment was ordered for patients who had critical laboratory results . Information technologies that facilitate the transmission of important patient data can potentially improve the quality of care OBJECTIVE to compare the ability of computer-aided diagnosis and contrast radiography for the diagnosis of acute mechanical small bowel obstruction . DESIGN Prospect i ve r and omised trial . SETTING Kaunas University of Medicine , Lithuania . SUBJECTS 80 patients with small bowel obstruction with no clinical evidence of strangulation who were r and omised into two groups ( n = 40 in each ) to be investigated by computer-aided diagnosis and contrast radiography . INTENVENTIONS : 37 patients required operation ( 46 % ) . MAIN OUTCOME MEASURES specificity , sensitivity , false positive and negative predictive values of the 2 methods ; time necessary to make the diagnosis ; and morbidity and mortality . RESULTS The specificity , sensitivity , positive and negative predictive values in the diagnosis of complete acute small bowel obstruction for the computer-aided group were 100 % , 87.5 % , 100 % and 92.3 % , and for the contrast radiography group 100 % , 76.9 % , 100 % and 90 % , respectively . The mean time period for making the diagnosis was 1 hour in the computer-aided group and 16 hours in the radiography group ( p < 0.001 ) . The overall mortality was 3 % and morbidity 9 % . CONCLUSION Computer-aided diagnosis had no significant advantage over contrast radiography in the accuracy of diagnosis of the character of small bowel obstruction . However , significantly less time was needed to make the diagnosis in the computer-aided group BACKGROUND Overuse of blood products is common , but prior efforts to improve transfusion decisions have met with limited success . STUDY DESIGN AND METHODS This study examines transfusion practice s before and after a conventional educational intervention followed by a r and omized controlled trial of a decision support ( DS ) intervention with computerized physician order entry ( CPOE ) for red blood cell , platelet , and fresh-frozen plasma orders . The study was conducted in an academic medical center between April 2003 and June 2004 . Orders originating from units not using CPOE with DS ( e.g. , the emergency department ) were excluded . Junior housestaff were r and omly assigned into a control group and an intervention group who received DS for transfusion orders . Transfusion orders were initially classified according to guideline rules as DS-agree or DS-disagree . Chart review s assessed inappropriateness for all DS-disagree orders and a sample of DS-agree orders . The total of inappropriate transfusion orders included chart review confirmed DS-disagree orders and DS-agree orders reclassified as inappropriate . RESULTS The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and r and omly assigned junior housestaff were 72.6 percent ( 2154/2967 ) and 71.9 percent ( 1259/1752 ) and improved after conventional education to 63.8 percent ( 1699/2663 ; p < 0.0001 ) and 63.3 percent ( 1263/1996 ; p < 0.0001 ) , respectively . The percentage of inappropriate orders in the DS intervention group continued to improve ( 59.6 % , 804/1350 ; p < 0.0001 ) . Physicians accepted 14 percent ( 133/939 ) of new DS-recommended orders , especially recommendations to increase transfusion doses ( 73 % ) . CONCLUSIONS Education and computerized DS both decreased the percentage of inappropriate transfusions , although the residual amount of inappropriate transfusions remained high OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits BACKGROUND Applied prospect ively to patients with peripheral arterial disease , individualized decision analysis has the potential to improve the surgeon 's ability to optimize patient outcome . METHODS A prospect i ve , r and omized trial comparing Markov surgical decision analysis to st and ard decision-making was performed in 206 patients with symptomatic lower extremity arterial disease . Utility assessment and quality of life were determined from individual patients prior to treatment . Vascular surgeons provided estimates of probability of treatment outcome , intended and actual treatment plans , and assessment of comfort with the decision ( PDPI ) . Treatment plans and PDPI evaluations were repeated after each surgeon was made aware of model predictions for half of the patients in a r and omized manner . RESULTS Optimal treatments predicted by decision analysis differed significantly from the surgeon 's initial plan and consisted of bypass for 30 versus 29 % , respectively , angioplasty for 28 versus 11 % , amputation for 31 versus 6 % , and medical management for 34 versus 54 % ( agreement 50 % , kappa 0.28 ) . Surgeon awareness of the decision model results did not alter the verbalized final plan , but did trend toward less frequent use of bypass . Patients for whom the model agreed with the surgeon 's initial plan were less likely to undergo bypass ( 13 versus 30 % , P < 0.01 ) . Greater surgeon comfort was present when the initial plan and model agreed ( PDPI score 47.5 versus 45.6 , P < 0.005 ) . CONCLUSIONS Individualized application of a decision model to patients with peripheral arterial disease suggests that arterial bypass is frequently recommended even when it may not maximize patient expected utility 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 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 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 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 & NA ; Dystocia , or slow labor , is the leading cause of first‐time cesarean sections . Current diagnostic guidelines for dystocia are vague , and there is no clear postoperative confirmatory evidence to assess the correctness of this diagnosis . For several decades , various professional organizations have indicated that cesarean rates could be lowered safely and have recommended levels that are far below national averages . The three major factors , of roughly equal importance , associated with cesarean for slow labor are the baby 's weight , the mother 's height , and the threshold at which the physician believes it is reasonable to intervene . The last is the only modifiable factor , and quality programs are a major part of changing medical behavior . By using two study design s , the effect of a mathematical method for evaluating labor progress on the rate of cesarean section was measured . In the prospect i ve r and omized clinical trial , the relative risk of cesarean in the experimental group was unchanged at 1.04 . In the pretest‐posttest analysis , the rates fell from 19.54 % to 17.04 % at 6 months and 16.62 % at 12 months 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 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 BACKGROUND Hospitalizations are an opportunity to provide preventive care . OBJECTIVE To determine if computer reminders , which we have shown to be effective in our ambulatory care setting , increasing the provision of inpatient preventive care . METHODS R and omized , controlled trial on the general medicine inpatient service of an urban , university-affiliated public hospital . Study subjects were 78 house staff rotating on the 6 general medicine services . The intervention was reminders to physicians printed on daily rounds reports about preventive care for which their patients were eligible , and suggested orders for preventive care provided through the physicians ' workstations . The preventive care guidelines were derived from the US Preventive Care Task Force recommendations . Compliance with preventive care guidelines and house staff attitudes toward providing preventive care to hospitalized patients were the main outcome measures . RESULTS No significant differences were seen between intervention and control physicians in compliance with preventive care guidelines in the aggregate or when individual preventive care actions individual preventive care actions were analyzed . This was true even though most physicians endorsed providing most kinds of preventive care for hospitalized patients . CONCLUSIONS Despite past success in increasing preventive care in the outpatient setting , we were unable , using a moderately intensive intervention , to increase the provision of preventive care during hospitalizations . The physicians providing care during the hospitalization were not the patients ' primary care physicians , which proved to be an important barrier . More intensive interventions , or more direct linkages between inpatient and outpatient care providers , may be required to overcome this resistance 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 Daily documentation and maintenance of medical record quality is a crucial issue in orthopaedic surgery . The purpose of the present study was to determine whether the introduction of a h and held computer could improve both the quantitative and qualitative aspects of medical records . METHODS A series of consecutive patients who were admitted for the first time to a thirty-six-bed orthopaedic ward of an academic teaching hospital for a planned operation or any other treatment of an acute injury or chronic condition were r and omized to daily documentation of their clinical charts on a h and held computer or on conventional paper forms . The electronic documentation consisted of a specially design ed software package on a h and held computer for bedside use with structured decision trees for examination , obtaining a history , and coding . In the control arm , chart notes were compiled on st and ard paper forms and were subsequently entered into the hospital 's information system . The number of documented ICD ( International Classification of Diseases ) diagnoses was the primary end point for sample size calculations . All patient charts were reread by an expert panel consisting of two surgeons and the surgical quality assurance manager . These experts assigned quality ratings to the different documentation systems by scrutinizing the extent and accuracy of the patient histories and the physical findings as assessed by daily chart notes . RESULTS Eighty patients were r and omized to one of the two documentation arms , and seventy-eight ( forty-seven men and thirty-one women ) of them were eligible for final analysis . Documentation with the h and held computer increased the median number of diagnoses per patients from four to nine ( p < 0.0001 ) , but it produced some overcoding for false or redundant items . Documentation quality ratings improved significantly with the introduction of the h and held device ( p < 0.01 ) with respect to the correct assessment of a patient 's progress and translation into ICD diagnoses . Various learning curve effects were observed with different operators . Study physicians assigned slightly better practicability ratings to the h and held device . CONCLUSIONS The preliminary data from this study suggest that h and held computers may improve the quality of hospital charts in orthopaedic surgery . LEVEL OF EVIDENCE Therapeutic study , Level I-1a ( r and omized controlled trial [ significant difference ] ) . See Instructions to Authors for a complete description of levels of evidence Context Decision making about thrombolysis in acute myocardial infa rct ion ( AMI ) can be difficult . The Thrombolytic Predictive Instrument ( TPI ) estimates the risk for death and hemorrhage with and without thrombolysis . Its effect on patient care is unknown . Contribution This r and omized trial of the TPI in emergency departments showed that printing TPI predictions on the admission electrocardiogram increased the frequency of reperfusion for inferior AMI but not anterior AMI . The effect of the TPI was greatest for women and for patients who required off-site consultation . Implication s The TPI is a tool to assure all patients the same st and ard of care . The Editors Emergent coronary reperfusion for acute myocardial infa rct ion ( AMI ) can be lifesaving for appropriate patients who are promptly recognized and treated ( 1 - 4 ) . However , in the emergency department setting , this prompt recognition can be difficult , especially for less-obvious c and i date s and when physician decision makers are not all on site . To assist in treatment decisions , the Thrombolytic Predictive Instrument ( TPI ) , incorporated into conventional computerized electrocardiography , prints on the electrocardiogram ( ECG ) text header its predictions of key outcomes of thrombolytic therapy : 30-day mortality , 1-year mortality , cardiac arrest , hemorrhagic stroke , and bleeding requiring transfusion ( 5 , 6 ) . Over the past decade , as a result of intensive efforts by physician leaders , the U.S. National Institutes of Health National Heart Attack Alert Program , organizations interested in quality of medical care , the pharmaceutical industry , and others ( 3 , 7 - 16 ) , more patients with AMI have received thrombolytic therapy and have received it sooner ( 17 ) . However , further improvement is needed ( 17 - 20 ) , especially for patients with AMI other than anterior AMI ( the category of AMI for which thrombolytic therapy was first recognized as effective [ 1 , 2 ] ) and for women ( who have received reperfusion therapy at lower rates than men [ 18 , 20 ] ) . Also needed are ways to support prompt , accurate decisions about reperfusion therapy in hospitals and in prehospital emergency medical service ( EMS ) setting s where consultation with off-site physicians may be required . The need for prompt recognition of potential benefit also applies to acute reperfusion by primary percutaneous transluminal coronary angioplasty ( PTCA ) , which may be equivalent to thrombolytic therapy or even preferable for some patients with AMI ( 21 - 25 ) . Thus , any method of increasing use of thrombolytic therapy should not interfere with the alternative use of PTCA , when indicated . To test whether the TPI addresses these needs , we did a r and omized , controlled , clinical effectiveness trial in the emergency departments of 28 diverse hospitals . We sought to determine whether the TPI would help physicians 1 ) identify patients needing thrombolytic therapy who would not otherwise have been identified ; 2 ) use thrombolytic therapy sooner ; 3 ) identify more c and i date s for overall coronary reperfusion , including medical thrombolysis or primary PTCA ; and 4 ) expedite decisions about reperfusion when physician decision makers are not all on site . Methods Study Sites Our study was done in 28 U.S. hospitals , including public , private , community , and tertiary care hospitals in urban , suburban , and rural areas : Bess Kaiser Medical Center ( Portl and , Oregon ) , Boston City Hospital ( Boston , Massachusetts ) , Box Butte General Hospital ( Alliance , Nebraska ) , Carney Hospital ( Dorchester , Massachusetts ) , Cedars-Sinai Medical Center ( Los Angeles , California ) , Chadron Community Hospital ( Chadron , Nebraska ) , Cooley Dickinson Hospital ( Northampton , Massachusetts ) , Decatur County Hospital ( Oberlin , Kansas ) , Franklin Medical Center ( Greenfield , Massachusetts ) , Huntington Hospital ( Huntington , New York ) , Lincoln Community Hospital ( Hugo , Colorado ) , Mary Lane Hospital ( Ware , Massachusetts ) , Memorial Health Center ( Sidney , Nebraska ) , Memorial Hospital ( Craig , Colorado ) , New Engl and Medical Center ( Boston , Massachusetts ) , Noble Hospital ( Westfield , Massachusetts ) , North Shore University HospitalGlen Cove ( Glen Cove , New York ) , Plains Medical Center ( Limon , Colorado ) , Presbyterian/St . Luke 's Medical Center ( Denver , Colorado ) , Regional West Medical Center ( Scottsbluff , Nebraska ) , Rhode Isl and Hospital ( Providence , Rhode Isl and ) , Silverheels Health Center ( Fairplay , Colorado ) , Southeast Colorado Hospital ( Springfield , Colorado ) , Sunnyside Medical Center ( Clackamas , Oregon ) , Swedish Hospital ( Engelwood , Colorado ) , Timberline Medical Center ( Granby , Colorado ) , University Hospital ( Boston , Massachusetts ) , and University HospitalStony Brook ( Stony Brook , New York ) . Patients and Intervention We included all consenting patients 35 years of age and older who 1 ) presented with AMI to any study hospital during the 22-month period beginning 24 April 1995 and 2 ) had , on presentation to the emergency department , detection of ST-segment elevation characteristic of AMI on an ECG . At study hospitals , software that generated the TPI predictions was installed on conventional computerized electrocardiographs ( Hewlett-Packard , Palo Alto , California ) so that ST-segment elevation characteristic of AMI was automatically detected . When this elevation was detected , the patient was automatically r and omly assigned to the control or the TPI group . R and omization did not delay obtaining an ECG or treatment . ( In accordance with Institutional Review Board approval [ given that usual ECGs and ECGs with TPI predictions both represent st and ard care and that it is necessary not to disrupt initial emergency care ] , we obtained written informed consent as soon as was practical after the initial ECG . ) For patients in the TPI group , the electrocardiograph automatically prompted the user to enter patient information needed to make the TPI predictions : age , sex , history of hypertension , history of diabetes , blood pressure , and time since onset of ischemic symptoms . The remaining variables , based on measurement of ECG waveforms , were automatically acquired by the electrocardiograph . Then the ECG was printed with the TPI predictions on its header . If any variables for the calculations were missing , predictions were not calculated and an alert listing the missing variables was printed . Entry of missing data , if available , was allowed . Predictions were not generated for patients older than 75 years of age ( 5 , 26 , 27 ) . For controls , the ECG was automatically printed with the header text customarily used in that emergency department . Data Collection and Analysis At presentation and during hospitalization , we collected sociodemographic information ; data on clinical features , ECGs , and all cardiac biomarker test results ( at minimum , serial creatine kinase MB tests ) at presentation and follow-up ; the triaging physician 's training level and specialty and whether he or she was emergency departmentbased ; whether on- or off-site ( telephone ) consultations were used in making the reperfusion treatment decision ; whether the patient received thrombolytic therapy and , if so , the time from onset of chest pain to receipt of therapy ; and whether the patient received primary PTCA . The TPI software allowed real-time acquisition of the clinical variables required for the TPI calculations and automatic acquisition of Q-wave , ST-segment , and T-wave measurements . Follow-up data needed to assign confirmed true diagnoses were collected from arrival at the emergency department through the 30-day follow-up visit . The overall 30-day follow-up rate was 100 % . Site physicians , blinded to study group assignments , used World Health Organization criteria ( 28 ) to assign confirmed diagnoses on the basis of presentation , clinical course , initial and follow-up ECGs , and biomarker tests . An AMI was classified as anterior if the patient had at least two contiguous ECG anterior leads with ST-segment elevation , regardless of whether this was accompanied by elevation elsewhere . Any AMI with no significant anterior ST-segment elevation was classified as inferior . Emergency department care was classified by whether consultation with an off-site physician was used in making the treatment decision . Hospital size , hospital type , presence of on-site emergency department staff , and physician type were used as potentially explanatory variables . Statistical Analysis Baseline comparisons of patient characteristics between the control and TPI groups were done by using t-tests for continuous variables and chi-square tests for categorical variables . Because of skewed distributions of times from symptom onset , median times from symptom onset to initial ECG were compared between groups by using the Wilcoxon rank-sum test . Chi-square tests for 2 2 tables were used to compare crude differences between groups in rates of use of thrombolytic therapy ; use of thrombolytic therapy within 1 hour of r and omization ; and overall use of reperfusion , including PTCA . The predictive discrimination of the TPI 's mortality predictions was measured by using the area under the receiver-operating characteristic ( ROC ) curve , estimated by the c statistic from the logistic regression model predicting the outcome with the predicted values as the sole independent variable . Relative risks and P values were derived from the 2 2 tables and chi-square tests . Analyses by AMI location and patient sex were also adjusted for hospital type ( urban teaching hospital , teaching-affiliated hospital , or community or rural hospital ) by using the CochranMantelHaenszel test . Hospital groupings were made before analyses were done and reflect similar characteristics and expected reperfusion rates . Commonality of the relative risk across hospital type was tested by using the BreslowDay chi-square statistic . We used SAS , version 8 ( SAS , Inc. , Cary , North Carolina ) for all analyses . Role of the Funding Source Neither the funding source nor the manufacturers of equipment or software had any role in the Many approaches to controlling costs under managed care rely on the ability to prospect ively identify the type or level of service a patient requires at the time of presentation . Although computers may effectively predict these factors , the impact of such a computer system is greatly dependent on its integration into the admission process . Three factors that influence the effectiveness of predictive screening using a computer were identified . They are detection , intervention and compliance . The effect of these factors was then measured in a prospect i ve r and omized trial evaluating the effectiveness of computerized preadmission screening for predicting the appropriateness of inpatient care . This paper examines the three factors and their impact on the effectiveness of the system . A mathematical model that relates the factors to the overall effectiveness of computerized preadmission screening is proposed and considered in a more general context 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 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 |
11,207 | 20,664,825 | Hard stabilization appliances , when adjusted properly , have good evidence of modest efficacy in the treatment of TMJD pain compared to non-occluding appliances and no treatment .
Other types of appliances , including soft stabilization appliances , anterior positioning appliances , and anterior bite appliances , have some RCT evidence of efficacy in reducing TMJD pain . | AIMS To conduct a systematic review with meta- analysis of r and omized controlled trials ( RCTs ) that have assessed the efficacy of intraoral orthopedic appliances to reduce pain in patients with temporom and ibular disorders affecting muscle and joint ( TMJD ) compared to subjects receiving placebo control , no treatment , or other treatments . | The aim of the present study was to compare the effect of transcutaneous electric nerve stimulation ( TENS ) with the flat occlusal splint in the treatment of temporom and ibular joint ( TMJ ) disk displacement without reduction . Thirty-one patients were included and r and omly selected to be treated 6 weeks with either TENS ( 90 Hz , 30 min , three times/day ) or with a flat occlusal splint ( 24 h/day . Those selected for the TENS group had one electrode placed over the painful TMJ and another electrode over the anterior temporal muscle . The splint group used a conventional flat occlusal splint with cuspid guidance . Both treatment groups visited the clinic once a week . Symptoms and signs were registered before and after treatment . The intensity of pain was recorded with a visual analogue scale ( VAS ) and with an electronic pocket-sized recorder ( Pain-Track ) carried 1 week before and also the last week of treatment for continuous registration of pain . Measured with the VAS , half of the patients treated with splints became pain-free or their TMJ pain improved at least 50 % both at rest and with jaw function compared with only 6 % in the TENS-treated group . With regard to strictly chewing pain , the VAS-registered pain improved in two-thirds of the splint group , compared with 50 % of the TENS group . With the Pain-Track device it was found that in most individuals pain was aggrevated at mealtimes . The conclusion was that flat occlusal splints in several respects are better than TENS in the treatment of symptoms associated with TMJ disk displacement without reduction BACKGROUND The authors compared the efficacy of bilateral balanced and canine guidance ( occlusal ) splints in the treatment of temporom and ibular joint ( TMJ ) pain in subjects who experienced joint clicking with a nonoccluding splint in a double-blind , controlled r and omized clinical trial . METHODS The authors r and omly assigned 57 people with signs of disk displacement and TMJ pain into three groups according to the type of splint : bilateral balanced , canine guidance and nonoccluding . The authors followed the groups for six months using analysis of a visual analog scale ( VAS ) , palpation of the TMJ and masticatory muscles , m and ibular movements and joint sounds . They used repeated analysis of variance and a chi(2 ) test to test the hypothesis . RESULTS The type of guidance used did not influence the pain reduction , yet both occlusal splints were superior to the nonoccluding splint , on the basis of the VAS . Despite similar outcomes in relation to opening , left lateral and protrusive movements , TMJ and muscle pain on palpation , subjects who used the occlusal splints had improved clinical outcomes . The frequency of joint noises decreased over time , with no significant differences among groups . Subjects in the groups using the occlusal splints reported more comfort . CONCLUSION The type of lateral guidance did not influence the subjects ' improvement . All of the subjects had a general improvement on the VAS , though subjects in the occlusal splint groups had better results that did subjects in the nonoccluding splint group AIMS To compare the short-term efficacy of treatment with a stabilization appliance compared with that of a non-occlusal , control appliance in patients with temporom and ibular disorders ( TMD ) of mainly myogenous origin . METHODS A r and omized , controlled trial was performed with 60 patients suffering from myofascial pain . Patients were r and omly assigned to a treatment or a control group . The treatment group was treated by means of a stabilization appliance and the control group by means of a non-occlusal appliance . Symptoms and signs were registered before and after 10 weeks of treatment . RESULTS Improvement of overall subjective symptoms was reported in both groups , but significantly more often in the treatment group than in the control group ( P = .000 ) . The prevalence of daily or constant pain showed a significant reduction in the treatment group ( P = .028 ) compared with the control group . There was a significant decrease in the number of tender masticatory muscles in the treatment group ( P = .018 ) compared with the control group . CONCLUSION The results of this short-term evaluation suggest that the stabilization appliance is more effective in alleviating symptoms and signs in patients with TMD of mainly myogenous origin than a control , non-occlusal appliance . The stabilization appliance can therefore be recommended for the therapy of these patients PURPOSE We performed a comparative evaluation of different types of splint therapy for anterior disc displacement without reduction ( ADDWR ) of the temporom and ibular joint . PATIENTS AND METHODS Seventy-four patients agreed to participate ( 65 females and 9 males ) . All patients were examined using a clinical temporom and ibular joint disorder examination protocol , including muscle palpation , m and ibular range-of-motion measurement , and joint sound detection . Additionally , the patients marked their pain ( during chewing , m and ibular movements , and rest position ) and limitation levels on a visual analog scale . Bilateral magnetic resonance images were acquired , confirming ADDWR in at least one joint . After clinical examination and imaging , r and omized splint therapy was provided : 38 patients received a centric splint , while 36 received a distraction splint . After 1 , 3 , and 6 months of therapy , outcome was evaluated using the Wilcoxon signed rank test for matched pairs . Success after 6 months was defined as improvement in active mouth opening of greater than 20 % and pain reduction ( on chewing ) of at least 50 % . Success was statistically verified using logistic regression test . RESULTS The improvements in mouth opening were significant in both groups . The improvements in pain on chewing , pain during other functions , pain at rest , functional limitation on chewing , and other functions were also comparable in both groups . However , the logistic regression test suggested that patients using centric splints were treated more successfully than the others ( confidence interval , 1.014 to 8.741 , odds ratio = 2.785 ) . CONCLUSIONS Centric splints seem to be more effective than distraction splints . Therefore , before the surgical treatment of ADDWR , centric splints should be used instead of distraction splints In order to evaluate and compare the effects of biofeedback and occlusal splint therapy on m and ibular dysfunction , 30 patients were r and omly divided into two treatment groups . The patients were women aged 20 - -40 years without any obvious organic reasons for their symptoms . There were no significant differences between the two groups before the start of treatment in respect of signs and symptoms of m and ibular dysfunction . One group used full coverage splints at night for 6 weeks . The other group received biofeedback training up to six times , 30 min per session . One month after completion of the therapy the patients were re-examined . Both groups showed a significant reduction in symptoms , both subjectively and clinical ly . No significant differences between the groups were found . The two treatments were thus equally effective in the short-term perspective in patients with signs and symptoms of m and ibular dysfunction Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were r and omly assigned to three treatment groups : ( I ) onlays to maintain disk repositioning , ( II ) flat occlusal splint , or ( III ) untreated controls . Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle . The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly . The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion . Clinical examinations were performed before and after 6 months of treatment . The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment . The signs and symptoms in the flat occlusal splint group were no different from those in the control group . It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays . The symptoms , however , returned when the onlays were removed after 6 months ; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients The aim of this study was to investigate if the difference in treatment outcome between patients provided with a stabilisation appliance and a control appliance was due to the treatment and /or other factors in patients with temporom and ibular disorders ( TMD ) of arthrogeneous origin . Sixty patients were assigned to two equally sized groups : a treatment group , treated with a stabilisation appliance , and a control group given a control appliance . Thirteen possible background variables for the treatment outcome were correlated to changes in severity of temporom and ibular joint ( TMJ ) pain on a verbal scale in the two patient groups . The logistic regression analyses revealed that , after correcting for the background variables , stabilisation appliance treatment was a strong explanatory factor for a positive treatment outcome , with a significance of P = 0.0013 compared to patients belonging to the control group . Background variables of significant importance for the treatment outcome were male sex ( positive ) ( P = 0.0268 ) , and severe or very severe TMJ pain ( negative ) ( P = 0.0034 ) . These findings indicate that not only the treatment with a stabilisation appliance but also sex and the intensity of the TMJ pain before treatment might influence the treatment outcome in patients with TMD of arthrogeneous origin The aim of the investigation was to compare the effect on signs and symptoms of temporom and ibular disorders ( TMD ) of two different interocclusal appliances . Thirty patients with signs and symptoms of TMD received either a stabilisation splint or a new kind of splint based on the concept of nociceptive trigeminal inhibition ( NTI ) . A clinical examination was performed and subjective symptoms were registered before start of treatment and after 3 and 6 months . All participants were offered to change to the other type of splint at the 3-month follow-up in case of no improvement or impairment of their symptoms . One subject in each group was lost early during the investigation . The mean time for taking impressions , to make inter-occlusal recording and to adjust the stabilisation splints was 17 minutes . The mean time to fit and adjust the NTI splints was 27 minutes . At the 3-month follow-up , 4 patients that had received NTI splints accepted the offer to change to stabilisation splints due to no improvement or impairment of their symptoms . These treatments were judged as failures . No one in the stabilisation splint group utilised the offer to change treatment . At the 6-month follow-up , 7 of the remaining 10 subjects with NTI splints reported some ( n = 1 ) or significant ( n = 6 ) improvement , 2 reported no change and one reported impairment . All 14 who had been treated with a stabilisation splint reported some ( n = 2 ) or significant ( n = 12 ) improvement . For all variables registered , the results were in favour for the stabilisation splint . One subject treated with a NTI splint exhibited an impaired occlusion at the 6-month follow-up One hundred and ten patients , 23 males and 87 females , participated in a comparative study of the effect of acupuncture and occlusal splint therapy . All the patients exhibited signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than six months . The participants were r and omly assigned to three groups ; acupuncture treatment , occlusal splint therapy or control . The patients were evaluated before and immediately after treatment/control time . Ten different subjective and /or clinical assessment variables were used in the evaluation of the treatment effects . Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged . In this short-term study , acupuncture gave better subjective results ( p < 0.001 ) than the occlusal splint therapy In a r and omized trial the effects of occlusal appliance and relaxation therapy , each combined with brief information , were compared with brief information only , in adolescents with temporom and ibular disorder ( TMD ) pain . One-hundred- and -twenty-two adolescents ( 93 F and 29 M aged 12 - 18 years ) were r and omly assigned to one of the following 3 groups : brief information + occlusal appliance ( BI + OA ) , brief information + relaxation therapy ( BI + RT ) , or brief information ( BI ) . Included were subjects reporting pain once a week or more often , in addition to receiving a diagnosis of TMD according to the Research Diagnostic Criteria ( RDC/TMD ) . They were evaluated before and after treatment and at a 6-month follow-up by means of self-reports and clinical assessment . The result revealed a significantly higher reduction in frequency of pain , in pain intensity ( visual analog scale [ VAS ] ) , and in a composite pain index ( intensity x frequency ) for patients treated with BI + OA compared with those treated with BI alone . In the BI + OA group , 60 % of the patients attained a clinical ly significant improvement ( at least 50 % or more ) on the pain index , a significantly higher proportion compared to that obtained in the other 2 treatment groups . Analgesic consumption was also significantly more reduced in the BI + OA group compared to the BI group . However , no significant differences were found between the treatment groups in jaw opening or in muscle and TMJ tenderness scores . Occlusal appliance was found to be superior to both relaxation therapy and brief information regarding pain reduction and can therefore be recommended when treating adolescents with TMD pain Stabilization appliances are commonly used in the treatment of temporom and ibular disorders ( TMD ) , although the treatment effects are not fully understood . This study evaluated the short-term efficacy of a stabilization appliance in patients with TMD of arthrogeneous origin , using a r and omized , controlled , and double-blind design . Sixty patients were assigned to two equally sized groups : a treatment group given a stabilization appliance and a control group given a control appliance . Improvement of overall subjective symptoms was reported in both groups but significantly more often in the treatment group than in the control group ( P = 0.006 ) . Frequency of daily or constant pain showed a significant reduction in the treatment group ( P = 0.02 ) compared with the control group . The results of this short-term evaluation showed that both the stabilization appliance and the control appliance had an effect on temporom and ibular joint ( TMJ ) pain . It is improbable that the difference observed between the groups is due to chance alone In the present study , we examined clinical and laser-evoked potentials ( LEP ) features in two groups of chronic tension-type headache ( CTTH ) patients treated with two different approaches : intra-oral appliance of prosthesis , aim ing to reduce muscular tenderness , and 10 mg daily amitriptyline . Eighteen patients suffering from CTTH ( IHS , 2004 ) participated in the study . We performed a basal evaluation of clinical features and LEPs in all patients ( T0 ) vs. 12 age- and sex-matched controls ; successively , patients were r and omly assigned to a two-month treatment by amitriptyline or intra-oral device appliance . The later LEPs , especially the P2 component , were significantly increased in amplitude in the CTTH group . Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency . Total Tenderness Score was significantly reduced in the group treated by the prosthesis . The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment . The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit , favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain . Both the interventions at the peripheral and central levels may interrupt this reverberating circuit , improving the outcome of headache From a total of 1344 consecutive patients referred to a TMD clinic , twenty-six patients fulfilled the strict inclusion criteria s of TMD of mainly muscular origin . Half of the patients were assigned to receive treatment with an interocclusal appliance , the treatment being performed by a dentist . The other half was instructed to perform individualized therapeutic jaw exercises , and this treatment was managed by a dental assistant . The treatment result was evaluated after six months . The two treatments had a positive and equal effect upon both signs and symptoms of TMD . A further follow-up by question naire one to four years after the final clinical examination showed a lasting treatment result in most patients . Many patients , however , continued to perform jaw exercises and /or to wear their appliances . This indicates that these two treatments are mostly symptomatic and not causal . The conclusion of the present investigation is that therapeutic jaw exercises , managed by a dentist or a dental assistant , is a cost effective treatment with a prognosis comparable to a treatment with an interocclusal appliance and can thus be recommended as the first therapy of choice in patients with TMD of mainly muscular origin Objective : To examine whether the anterior repositioning splint is suitable treatment for temporom and ibular joint disc displacement with reduction and to determine the most appropriate pattern of usage . Design : Prospect i ve r and om control clinical trial . Setting : Dental school clinic unit . Subjects : Three groups of patients were treated , wearing the splint either during the day or at night or all the time . Results : 69 % of patients could be classed as improvers , by subjective and objective assessment s , at final review ( 3 months after treatment with an anterior repositioning splint ) . 88 % of patients who wore the splint for 24 hours per day improved over the 3-month period ; this improvement was statistically significant when compared with the other two groups . Conclusions : An anterior repositioning splint is an appropriate method of treatment for disc displacement with reduction . Patients should wear the splint 24 hours a AIMS To evaluate the long-term effectiveness of a brief skills training program for the management of chronic facial muscle pain . This program of physical self-regulation ( PSR ) involved primarily training in breathing , postural relaxation , and proprioceptive re-education . METHODS Physical self-regulation training was presented by a dentist during two 50-minute sessions spaced at 3-week intervals and was compared to a st and ard dental care ( SDC ) program that included a flat-plane intraoral appliance and self-care instructions provided by a dentist . Participants ( n = 44 ) were initially evaluated by a dentist experienced in the diagnosis and management of orofacial pain and were determined to have myofascial pain ( Type 1a and 1b diagnoses per the Research Diagnostic Criteria ) prior to r and om assignment to either the PSR or SDC conditions . Posttreatment evaluations 6 weeks and 26 weeks after treatment had begun were conducted by a dentist who was not aware of which treatment the participants received . RESULTS Initial results indicated that pain severity and life interference from pain were reduced in both groups ( P < 0.001 ) , while perception of control was increased ( P < 0.001 ) , as was incisal opening without pain ( P < 0.05 ) . At the 26-week follow-up , the PSR group reported less pain ( P < 0.04 ) and greater incisal opening , both with ( P < 0.04 ) and without ( P < 0.01 ) pain , than the SDC group . There were also significant decreases ( P < 0.05 ) in affective distress , somatization , obsessive-compulsive symptoms , tender point sensitivity , awareness of tooth contact , and sleep dysfunction for both groups over time . CONCLUSION The findings support the use of PSR for the short- and long-term management of muscle pain in the facial region . These results are discussed in terms of the potential mechanisms by which self-regulation treatment strategies are effective for the management of these pain disorders Fifty-five patients ( 46 women and 9 men ) with craniom and ibular disorders and a history of pain of at least 6 months ' duration participated in this trial . The patients were r and omly assigned to three groups : one group to receive acupuncture ; one group to receive occlusal splint therapy ; and one group to act as controls . Pressure pain threshold , clinical dysfunction score , and visual analog scale measures were used to evaluate patients before , immediately after , and 6 months after treatment . A moderate , but statistically significant , correlation was found between pressure pain threshold and the number of tender spots in the masticatory muscles ( tau = -.43 ; P < .001 ) , degree of tenderness in the masticatory muscles ( tau = -.43 ; P < .001 ) , clinical dysfunction score ( tau = .32 ; P < .001 ) , and the visual analog scale ( tau = -.25 ; P < .01 ) . The short-term results showed a statistically significant improvement in all evaluations for both treatment groups . No significant differences were found in the control group . The improvements result ed in significant differences between the control and each treatment group immediately after treatment . At the 6-month follow-up , no significant differences in pressure pain threshold or clinical dysfunction score were found in the two treatment groups compared with the short-term results Orthopedic m and ibular repositioning and flat plane occlusal splint therapy were compared in the treatment of 20 patients with internal TMJ derangement with reduction . The following conclusions can be drawn . M and ibular repositioning treatment produces significant subjective and objective improvement in the dysfunction of patients with internal joint derangements with reduction . Flat plane occlusal splint treatment produces no significant change in the dysfunction level of patients with internal joint derangements with reduction . M and ibular repositioning treatment may eliminate the reciprocal click of internal joint derangement with reduction . To realize improvement in dysfunction of internal joint derangement , it appears that the reciprocal click must be eliminated . M and ibular repositioning treatment produces a significant improvement in muscle pain associated with internal joint derangement A prospect i ve r and omized study was carried out to compare the therapeutic success of two different types of splint in patients with painful anterior disc displacement of the temporom and ibular joint . The patients in Group I ( n = 20 ) received stabilization splint therapy and the patients in Group II ( n = 20 ) pivot splint therapy . Clinical investigation of the craniom and ibular system was performed before and 1 , 2 and 3 months after therapy and this was accompanied by subjective evaluation by the patients of their symptoms , using a vali date d question naire with visual analogue scales ( VAS ) . There was a significant increase in maximum jaw opening and a significant reduction in subjective pain in both groups during the course of therapy ( Wilcoxon test , P < 0.05 ) . Active jaw opening increased by a mean of 8.05 mm in the group of patients treated with a stabilization splint ( Group I ) . The comparable figure with pivot splint therapy ( Group II ) was 8.26 mm . The VAS scale value in Group I was reduced by 30.54 units and in Group II by 39.36 scale units . However , neither of these differences between the groups was statistically significant ( Mann-WhitneyU-test , P > 0.05 ) . It can be concluded that both types of splint provided effective therapy in patients with anterior disc displacement Objective . To compare splint therapy in temporom and ibular disorder ( TMD ) patients using two splint design s. Material and methods . In a double-blind r and omized parallel trial , 40 consenting patients were selected from the dental faculty pool of TMD patients . Two splint design s were produced : an ordinary stabilization ( Michigan type ) and a NTI ( Nociceptiv trigeminal inhibition ) . The differences in splint design were not described to the patients . All patients were treated by one operator . A separate , blinded , examiner assessed joint and muscle tenderness by palpation and jaw opening prior to splint therapy , and after 2 and 6 weeks ' and 3 months ' splint use during night-time . The patients reported headache and TMD-related pain on a visual analog scale before and after splint use , and were asked to describe the comfort of the splint and invited to comment . Results . Thirty-eight patients with mainly myogenic problems were observed over 3 months . A reduction of muscle tenderness upon palpation and self-reported TMD-related pain and headache and an improved jaw opening was seen in both splint groups ( p<0.05 ; paired t-test and Wilcoxon signed-ranks tests ) . There were no changes for TM joint tenderness upon palpation . No differences were noted between the two splint design s after 3 months for the chosen criteria of treatment efficacy ( p>0.05 ; Mann-Whitney U-test ) . Conclusion . No differences in treatment efficacy were noted between the Michigan and the NTI splint types when compared over 3 months AIMS To investigate the efficacy of the anterior repositioning splint and the canine-protected splint in relieving the signs and symptoms of anterior disc displacement with reduction , and to evaluate the effects of both splints on disc position using a st and ardized magnetic resonance imaging measurement technique . MATERIAL AND METHODS A sample of 18 adult subjects was studied . The joint disorder was dually diagnosed via pretreatment clinical examination and magnetic resonance imaging . The sample was r and omly divided into two groups . In the first group , each subject received an anterior repositioning splint ; in the second group , each subject received a canine-protected splint . The treatment lasted 3 months . A st and ardized magnetic resonance imaging 10-step procedure was developed . Posttreatment clinical examinations and magnetic resonance imagings were done . Pretreatment and posttreatment records were statistically compared . RESULTS AND CONCLUSIONS Both types of splints were effective in eliminating pain and clicking . All magnetic resonance imaging measurements showed that the canine-protected splint was superior to the anterior repositioning splint , as it allowed the articular disc to resume its normal length and shape while moving in a posterior direction toward recapture . Disc recapture was demonstrated via magnetic resonance imaging in 25 % of the subjects from the anterior repositioning splint group , in 40 % of the subjects from the canine-protected splint group , and in 33.3 % of the subjects from both groups . Thus , noninvasive treatment techniques ( such as occlusal splint therapy ) might be the treatment of choice for anterior disc displacement with reduction Eighty patients , of whom 22 were men and 58 women , participated in a 1-year follow-up study . All participants in the study showed signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than 6 months at treatment start . The patients were r and omly assigned to either acupuncture or occlusal splint therapy . Those patients who did not respond to either of the treatment modes were offered various additional therapies . The result showed that 57 % of the patients who received acupuncture and 68 % of the patients treated with occlusal splint therapy benefited subjectively ( p < 0.01 ) and clinical ly ( p < 0.001 ) from the treatment over a 12-month period . No statistically significant difference was found between the two groups as to the assessment variables . Those patients who received various additional therapies after acupuncture and /or occlusal splint therapy responded favorably to additional treatment in only a few instances . The study showed that acupuncture gave positive results similar to those of occlusal splint therapy in patients with primarily myogenic CMD symptoms over a 1-year follow-up period Objective : To examine whether the stabilisation splint is a suitable treatment for pain dysfunction syndrome and to determine the most appropriate pattern of usage . Design : Prospect i ve r and om control clinical trial . Setting : Dental school clinic unit . Subjects : 70 patients diagnosed with pain dysfunction syndrome were treated with a stabilisation splint for 3 months . Group 1 ( 23 patients ) wore the splint 24 hours/day . Group 2 ( 19 patients ) wore the splint only during the day . Group 3 ( 28 patients ) wore the splint only at night . Results : There was no statistically significant advantage to any pattern of splint usage ; all groups showed a marked improvement by subjective and objective assessment . Conclusions : Patients being treated for pain dysfunction syndrome by a stabilisation splint need wear the splint only at Forty-eight dysfunctional patients ( i.e. , high levels of pain , interference , and affective distress and low levels of perceived control ) with temporom and ibular disorders ( TMDs ) were r and omly assigned either to a treatment consisting of an intraoral appliance ( IA ) and stress management with biofeedback ( SM ) plus nondirective , supportive counseling ( SC ) -- IA + SM + SC -- or to a customized treatment that included cognitive therapy ( CT ) with the IA and SM -- IA + SM + CT . Both treatment groups reported statistically significant reductions on a set of physical , psychosocial , and behavioral measures posttreatment and at a 6-month follow-up . However , the intervention that included CT demonstrated significantly greater reductions in pain , depression , and medication use . Only the groups receiving the treatment that included the CT demonstrated continued improvements to the follow-up on pain associated with muscle palpation , self-reported pain severity , depression , and use of medications . These results support the efficacy of the tailored treatment for dysfunctional TMD BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application Fifty-five of 100 chronic headache patients , referred consecutively to a neurologist , exhibited craniom and ibular pain during examination of the stomatognathic system . This suggests a possible relationship between the headaches and the condition of the masticatory muscles . The patients were r and omly divided into two groups . One group was treated by a neurologist and the other by a dentist . More of the patients treated by the dentist reported a decreased intensity of the headache ( P less than 0.025 ) or a reduction in medication ( P less than 0.05 ) . Changes in headache frequency were also reported more often in the craniom and ibular disorder treatment group ( P less than 0.025 ) PURPOSE The purpose s of this study were to compare changes in the condyle-fossa relationship in patients with temporom and ibular disorders of arthrogenous origin treated with either a stabilization or a control appliance in a double-blind controlled study , and to compare the changes in the condyle-fossa relationship with the short-term treatment effect in the two treatment groups . The radiographic appearance of the temporom and ibular joint was also studied . MATERIAL S AND METHODS Fifty-eight patients with temporom and ibular disorders of arthrogenous origin were assigned to two equally sized groups : a treatment group given a stabilization appliance ; and a control group , given a control appliance . The study covered 10 weeks . The treatment outcome regarding changes in severity of temporom and ibular joint pain on a verbal scale was compared to changes in the condyle-fossa relationship in horizontally corrected oblique lateral transcranial radiographs taken with and without the appliance . Condyle-fossa relationship and structural bone changes were observed before treatment in corrected lateral tomograms . RESULTS The group treated with a stabilization appliance showed a changed condylar position significantly more often ( P = 0.004 ) than the control group . Of the patients reporting a successful treatment outcome , significantly more ( P = 0.006 ) showed a changed condyle position in the group treated with a stabilization appliance than in the group treated with a control appliance . CONCLUSION In patients with temporom and ibular disorders of arthrogenous origin , the short-term occlusal appliance therapy result ing in a changed condylar position gave relief of symptoms more often than if the condylar position was unchanged Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes Twenty patients with m and ibular dysfunction , all women , aged 17 - 41 years , were r and omized for treatment with either a bite plate with a frontal plateau or a full-coverage stabilization splint . The occlusal appliances were used at night for 6 weeks to compare clinical and electromyographic effects ( EMGs ) . Integrated EMGs were recorded bilaterally from the anterior and posterior parts of the temporal muscle and the masseter muscle in the rest position and during gentle and maximal biting before and after treatment without the appliances in situ . Initially recorded EMG activity in the temporal muscle was correlated to signs of dysfunction in the rest position . Compared with previously investigated healthy subjects , the patients had lower EMG activity in the anterior part of the temporal muscle and in the masseter muscle during maximal biting . Use of occlusal appliances at night for 6 weeks did not change the EMG activity in the rest position or during maximal biting . The clinical signs improved , significantly in the splint group . The subjective symptoms improved in both groups , significantly more in the splint group This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature . Twenty-one females meeting specific criteria were r and omly assigned to one of three treatment conditions : a dental splint and physiotherapy program ; a relaxation program utilizing progressive muscle relaxation , biofeedback , and stress management techniques ; or a minimal treatment program involving transcutaneous electrical nerve stimulation . Improvement was assessed through a dental examination , self-monitoring of pain , and an assessment of EMG activity during resting and task conditions . Significant changes were obtained in response to all treatment programs . The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain . The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw A flat occlusal splint has been extensively used in the treatment of patients with temporom and ibular joint disk displacement without reduction , but no studies with untreated controls have assessed its effect . We r and omly assigned 51 patients with temporom and ibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial . Pain symptoms disappeared in about one third of the patients in each group . Another third of the patients in the control group improved . Sixteen percent of the patients in the control group and 40 % of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study . Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group . A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction . The use of a flat occlusal splint in this patient group should therefore be reconsidered BACKGROUND The research literature reaches inconsistent conclusions about the efficacy of oral splints for treating myofascial face pain . This investigation hypothesizes that their effectiveness varies as a function of the presence or absence of widespread pain . METHODS In a r and omized , controlled clinical trial , 63 women with myofascial face pain were assigned to use of either an active , maxillary , flat-plane , hard acrylic splint or a palatal splint that did not interfere with occlusion . Participants also were classified according to the presence or absence of widespread pain throughout the body . After six weeks , groups were compared regarding pain on palpation , self-reported pain and functional outcome . RESULTS Overall , the findings showed a modest tendency for subjects receiving the active vs. the palatal splint to exhibit improvement on self-reported pain and functional outcome . On further division of the sample into subjects with local vs. widespread pain , the general pattern showed that patients with widespread pain who received an active splint did not experience improvement , while patients with local pain who received the active splint did . CONCLUSIONS The presence or absence of widespread pain may help to define the specific circumstances under which oral splints should be prescribed for patients with myofascial face pain . CLINICAL IMPLICATION S Clinicians should screen patients with myofascial face pain for the presence of widespread pain , since this comorbid symptom pattern may be a contraindication for the use of oral splints A crossed- design experimental study has been made involving simple blind paired data and r and om assignment to treatment , with the aim of evaluating the action of an occlusal splint with transcutaneous electric nerve stimulation ( TENS ) upon the manifestations of temporom and ibular disorders ( TMD ) in patients with bruxism . The prevalence of TMD in the 24 patients with bruxism was 62.5%% ; the corresponding severity , as determined by the pantographic reproducibility index ( PRI ) , was mild ( mean value : 20.71 ) . Clicking and pain in the lateral pterygoid muscle were the most frequent clinical manifestations . The occlusal splint and TENS did not significantly improve the signs and symptoms of TMD in these patients with bruxism & NA ; Oral splints are widely used in the treatment of myofascial pain of masticatory muscles , even though their mechanism of action is unknown . The present study evaluated the therapeutic efficacy of splints using a parallel , r and omized , controlled and blind design . Following a sample size estimation , 63 subjects were recruited and assigned to 3 groups : ( 1 ) passive control : full occlusal splint worn only 30 min at each appointment : ( 2 ) active control : palatal splint worn 24 h/day : and ( 3 ) treatment : full occlusal splint worn 24 h/day . On each of 7 visits over 10 weeks , subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication . The effect of pain on the quality of life was also rated on category scales . All pain ratings decreased significantly with time , and quality of life improved for all 3 groups . However , there were no significant differences between groups in any of the variables . These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain , as well as the improvement of quality of life during the trial , was non‐specific and not related to the type of treatment ABSTRACT Migraine and tension-type headaches have always plagued mankind . In spite of all the research dollars spent trying to determine the etiologies of these headaches , the neurology community still has not established a known cause of migraine and tension type headaches . This paper describes a study that was conducted for the U.S. Food and Drug Administration in which the efficacy of the Nociceptive Trigeminal Inhibition Tension Suppression System was evaluated and proved safe and efficacious in the reduction of medically diagnosed migraine and tension-type headache The long-term treatment effects of biofeedback and occlusal splints on m and ibular dysfunction were compared . Thirty female patients were r and omly divided into two treatment groups . One group had full coverage splints , the other group received biofeedback training . At the re-examinations 1 and 12 months after completion of therapy , the subjective and clinical symptoms were significantly reduced in both groups . No significant differences between the groups were found . A stepwise analysis of regression indicated that biofeedback training may be a useful alternative to splint therapy in cases where night time bruxing is not the dominating feature Thirty patients with craniom and ibular disorders and headache were r and omly divided into two groups . One received occlusal equilibration ( O group ) and the other ( S group ) routine stomatognathic treatment , including an occlusal splint . The outcome of treatment was evaluated by means of a question naire , visual analogue scales , and clinical examination . In both groups , the patients reported reduction of symptoms , but the clinical dysfunction score used was significantly diminished only in the S group . A combined treatment regimen , including an occlusal splint , was more effective than occlusal adjustment alone , especially with regard to clinical signs of dysfunction Occlusal splints were adjusted to different vertical heights and used to single out the influence of vertical dimension of occlusion in increments on BT-EMG activity of the masseter muscle in patients with m and ibular dysfunction . The vertical dimension of least EMG activity was determined for each of 60 patients , who were r and omly divided into three groups according to the vertical dimension at which the occlusal splint was adjusted : group No. 1 , 1 mm from occlusal vertical dimension ; group No. 2 , mean vertical dimension , 4.25 mm ; group No. 3 , mean vertical dimension , 8.25 mm . Results showed a significant reduction of masseter BT-EMG activity ( series A and B ) at the end of the 3-week treatment period for patients in group Nos. 2 and 3 in comparison with group No. 1 . Furthermore , the short-term use of occlusal splints with a vertical height that exceeded the so-called physiologic interocclusal distance did not result in an increase in masseter BT-EMG activity . This study suggests that an increase of vertical dimension of occlusion to or near the vertical dimension of least EMG activity by means of occlusal splints can be an effective way to obtain a reduction in masseteric muscle activity Occlusal splints constructed at three different vertical heights were used to study the influence of vertical dimension in the etiology of bruxism and MPD syndrome . The vertical dimension of least EMG activity was determined for each of 75 patients who were r and omly divided into three groups according to the vertical dimension at which the occlusal splint was constructed . Group I occlusal splints were constructed at 1 mm from the occlusal vertical dimension , group II splints at 4.42 mm , and group III splints at 8.15 mm . Results showed a faster and more complete reduction in clinical symptoms for groups II and III than for group I. The temporary use of occlusal splints with a vertical height exceeding the physiologic rest position did not encourage a greater muscular tonus or hyperactivity of jaw muscles . It can be concluded that elongation of elevator muscles to or near the vertical dimension of least EMG activity by means of occlusal splints is more effective in producing neuromuscular relaxation |
11,208 | 23,543,549 | Limited evidence suggests that women generally seem satisfied with their care .
The available evidence suggests that medical treatment , with misoprostol , and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service re sources to support all three approaches . | BACKGROUND Miscarriage occurs in 10 % to 15 % of pregnancies .
The traditional treatment , after miscarriage , has been to perform surgery to remove any remaining placental tissues in the uterus ( ' evacuation of uterus ' ) .
However , medical treatments , or expectant care ( no treatment ) , may also be effective , safe and acceptable .
OBJECTIVES To assess the effectiveness , safety and acceptability of any medical treatment for incomplete miscarriage ( before 24 weeks ) . | OBJECTIVE The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution . STUDY DESIGN Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned r and omly to receive either 800 microg of misoprostol with saline solution ( group I , 41 women ) or without ( group II , 39 women ) . Treatment was repeated on day 3 if the gestational sac remained . Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up . Data were analyzed with the Student t test and the chi(2 ) or Fisher exact test . RESULTS By the first follow-up visit , 73 % ( group I ) and 64 % ( group II ) of women passed the gestational sac ( P=.38 ) . By the second follow-up visit , expulsion rates were 83 % and 87 % , respectively ( P=.59 ) . Five subjects in each group underwent curettage . CONCLUSION Misoprostol is effective for the treatment of failed first-trimester pregnancy . The expulsion rate is not improved by adding saline solution BACKGROUND We aim ed to compare patients ' health-related quality of life after a misoprostol strategy to a curettage in women with early pregnancy failure after failed expectant management . METHODS A multicentre r and omized clinical trial was performed in The Netherl and s. In all , 154 women with early pregnancy failure confirmed at ultrasonography who had been managed expectantly unsuccessfully for > or = 1 week were r and omly assigned to undergo either treatment with misoprostol ( n=79 ) or curettage ( n=75 ) . The main outcome measures were health-related quality of life and satisfaction with treatment . RESULTS In the misoprostol strategy 47 % of the women needed additional curettage , as compared to 4 % after curettage . In both groups , health-related quality of life was impaired most severely 2 days after treatment . In the misoprostol group , health-related quality of life was more severely impaired ; after 2 days this was due to more pain and after 2 and 6 weeks this was due to a worse general health perception . Health-related quality of life was temporarily significantly more impaired in women in whom misoprostol failed as compared to women in whom misoprostol treatment was successful . In both treatment groups , an equal percentage of women ( 58 % ) would choose the same treatment in the future . In women treated with misoprostol , however , this choice depended on the initial success of misoprostol : in cases where misoprostol had caused complete evacuation , 76 % of the women would opt for the same treatment , whereas only 38 % of women who needed curettage after unsuccessful misoprostol would do so ( P<0.01 ) . CONCLUSION Our study shows that , although both the misoprostol strategy and the curettage strategy result ed in complete evacuation in the end , women are willing to accept some disadvantages of misoprostol to avoid curettage . A treatment inconvenience using misoprostol is accepted as long as initial evacuation rate is high . This finding should be an integral part of counselling women when deciding upon management of early pregnancy failure BACKGROUND Responses to miscarriage range from relief to devastation , yet there have been no r and omized controlled studies that demonstrate significant effects of counseling with women who miscarry . OBJECTIVE To test the effects of caring-based counseling , measurement , and time on the integration of loss ( miscarriage impact ) and women 's emotional well-being ( moods and self-esteem ) in the first year after miscarrying . METHOD ANCOVA was used in this r and omized , longitudinal Solomon four-group experimental investigation . Enrolled were 242 ; 185 completed . Outcomes included : self-esteem , overall emotional disturbance , anger , depression , anxiety , confusion , overall miscarriage impact , personal significance , devastating event , lost baby , and isolated . RESULTS During the first year after loss ( a ) caring was effective in reducing overall emotional disturbance , anger , and depression ; and ( b ) time passing led to increased self-esteem and decreased anxiety , depression , anger , confusion , and personal significance of loss . CONCLUSION Caring , measurement , and time had some positive and significant effects on the integration of loss and enhancement of well-being in the first year subsequent to miscarrying BACKGROUND Dilatation and curettage ( D&C ) has been the usual treatment for early pregnancy failure ( EPF ) . Medical management with misoprostol may be an effective alternative . Bleeding patterns during and after medical management of EPF are unknown . METHODS A prospect i ve cohort study was conducted at University-based clinics and physician offices . Eighty women < 11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled . Treatment consisted of either 800 micro g of moistened ( 2 ml of saline ) or dry vaginal misoprostol . Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary . Haemoglobin was assessed at enrollment and 2 weeks later . RESULTS After misoprostol treatment , patients reported bleeding or spotting every day for the 14 days observed . Self-assessed heavy bleeding days were few ( median 3 ) and usually occurred immediately after treatment . Sanitary pad use was highly variable ( mean 30.5 , range 2 - 125 pads over the 2 week period ) and not related to changes in haemoglobin . The mean decrease in haemoglobin was 0.5 g/dl ( SD 1.2 ) . Complete expulsion without D&C occurred in 85 % of subjects . CONCLUSIONS Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common . Heavy bleeding is usually limited to a few days after treatment . Clinical ly important changes in haemoglobin are rare OBJECTIVE The purpose of this study was to compare the psychologic impact and client satisfaction of routine surgical evacuation of the uterus with medical evacuation in cases of spontaneous abortion . STUDY DESIGN This was a prospect i ve , r and omized controlled trial . Two hundred eighteen women who were admitted to a university teaching hospital after spontaneous abortion and who consented to the study were r and omized to routine surgical evacuation or medical evacuation of the uterus with the use of misoprostol . General psychologic well-being , level of depression , fatigue symptoms , psychiatric morbidity , social functioning , client satisfaction , and acceptance were measured in the 2 groups . RESULTS The 2 groups did not differ in any of the measured psychological outcomes . Significantly more participants who experienced successful evacuation of the uterus with the misoprostol protocol would choose the same mode of treatment if they were able to choose again . However , participants for whom the medical treatment failed to evacuate the uterus and subsequent surgical evacuation was required are significantly less satisfied with the treatment . CONCLUSION Medical treatment of spontaneous abortion with misoprostol is psychologically safe and more compatible with the ethnomedical beliefs of our Chinese participants . Client satisfaction and acceptance should be taken into consideration in the evaluation of treatment outcomes OBJECTIVE To evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure . DESIGN As part of a r and omized clinical trial , serum was collected on treatment days 1 , 3 , 8 , and 15 . SETTING Multicenter clinical trial . PATIENT(S ) Women with a nonviable first-trimester pregnancy . INTERVENTION(S ) Serum concentrations of human chorionic gonadotropin ( hCG ) , progesterone , and sex hormone binding globulin ( SHBG ) were evaluated . MAIN OUTCOME MEASURE(S ) A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and /or successful management . RESULT ( S ) The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone ( P ) ( P<.005 ) and hCG ( P<.005 ) , but not for SHBG . The actual value was not significantly associated with complete expulsion or successful management . A decrease ( day 1 - 3 ) of 79 % for both hCG and P was associated with a 90 % probability of complete passage of the gestational sac . A 90 % probability of successful management was noted if P decreased by 78 % on day 3 or 59 % on day 7 , or hCG decreased by 74 % on day 3 or 78 % on day 7 compared with pretreatment values . CONCLUSION ( S ) Percent change , but not absolute change , in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success BACKGROUND The increased pressure on health care expenses implies that physicians should consider economic aspects as part of the clinical decision-making process . Direct and indirect costs of a strategy starting with misoprostol in treatment of early pregnancy failure as compared to curettage is therefore performed . METHODS We performed a cost-minimization analysis alongside a multicentre r and omized trial . Clinical data and data on the use of medical re sources were obtained from a r and omized trial comparing misoprostol and curettage , which had shown that misoprostol reduced the need for curettage in 53 % . In a sensitivity analysis the percentage of women who needed curettage after misoprostol varied between 25 and 90 % . RESULTS Direct costs per case were significantly lower in the misoprostol group ( mean 433 ) than in the curettage group ( mean 683 ) ( mean difference 250 , 95 % CI 184 to 316 , P < 0.001 ) . These significant differences existed under a wide range of alternative assumptions about unit costs . The differences in direct cost in favour of misoprostol were large for women who had complete evacuation after initial misoprostol treatment as compared to those who needed additional curettage after failed misoprostol . Mean indirect costs were equal for both groups ( misoprostol mean 486 ; curettage mean 428 ; mean difference 60 , 95 % CI -61 to 179 , P = 0.51 ) . The mean total costs for a strategy starting with misoprostol was 915 versus 1107 for curettage , with a mean difference between both groups of 192 ( 95 % CI 33 to 351 , P = 0.04 ) . An increase of the complete evacuation rates for initial misoprostol therapy to 90 % in the sensitivity analysis increased the cost difference between misoprostol and curettage to 550 . CONCLUSION The use of misoprostol for early pregnancy failure after failed expectant management is less costly than curettage Objectives To compare fertility rates after the three methods of managing early miscarriage in women recruited to the MIST ( miscarriage treatment ) r and omised controlled trial . Setting Early pregnancy clinics of acute hospitals in the south west region of Engl and . Participants 1199 women who had had an early miscarriage ( < 13 weeks ) confirmed by scan . Intervention Expectant , medical , or surgical management . Main outcome measures Self reported pregnancy rates and live birth rates . Results Of 1199 women recruited to the trial , 1128 consented to follow-up . Of these , 762 women replied giving pregnancy details ( 68 % response rate ) . Respondents were representative of the trial participants . The live birth rate five years after the index miscarriage was similar in the three management groups : 177/224 ( 79 % , 95 % confidence interval 73 % to 84 % ) in the expectant management group , 181/230 ( 79 % , 73 % to 84 % ) in the medical group , and 192/235 ( 82 % , 76 % to 86 % ) in the surgical group . There was also no significant difference according to previous birth history . Older women and those with previous miscarriages were significantly less likely to subsequently give birth . Conclusion Method of miscarriage management does not affect subsequent pregnancy rates with around four in five women giving birth within five years of the index miscarriage . Women can be reassured that long term fertility concerns need not affect their choice of miscarriage management . Trial registration National Research Register N0467011677/N0467073587 Objective To estimate and compare the costs of surgical and medical treatment of miscarriage to the National Health Service OBJECTIVES To assess if there was any potential relationship between endometrial thickness and final treatment outcome in women successfully treated with misoprostol for a first trimester anembryonic gestation , embryonic demise or fetal demise . METHODS Eighty women were treated with up to two doses of misoprostol 800 microg vaginally for early pregnancy failure . Subjects were scheduled to return 2 ( range 1 - 4 ) , 7 ( range 5 - 9 ) and 14 ( range 12 - 17 ) days after treatment . Transvaginal ultrasonography was performed at each follow-up visit . RESULTS The median endometrial thickness at each of the follow-up visits for women who had expelled the gestational sac was 14 mm , 10 mm , and 7 mm , respectively . The endometrial thickness at the first follow-up visit exceeded 15 mm in 20 subjects ( 36 % ) and 30 mm in four subjects ( 7 % ) . Only three women had a suction aspiration for bleeding after documented expulsion . The endometrial thickness for these women was 11 , 13 , and 14 mm at the first follow-up visit . CONCLUSIONS There is no obvious relationship between increasing endometrial thickness and the need for surgical intervention in women treated with misoprostol for early pregnancy failure Objective To compare the pharmacokinetics of vaginal and oral administration of the prostagl and in E1 analogue , misoprostol . Methods Twenty women received 400-μg doses of misoprostol either orally or as tablets placed in the vagina . Serum levels of the principal metabolite , misoprostol acid , were measured at 7.5 , 15 , 30 , 45 , 60 , 90 , 120 , and 240 minutes . The first ten women were pregnant and undergoing firsttrimester abortions , and the last ten were not pregnant and had additional blood sampling at 360 minutes . We compared the pharmacokinetics of misoprostol acid after oral and vaginal administration . Results All 20 subjects completed the study . The maximum mean ( ± st and ard deviation [ SD ] ) of misoprostol acid differed significantly between the oral and vaginal groups ( 277 ± 124 compared with 165 ± 86 pg/mL , respectively ; P = .03 , analysis of variance ) , as did the mean ± SD time to peak levels ( 34 ± 17 compared with 80 ± 27 minutes , respectively ; P < .001 ) and areas under the misoprostol concentration versus time curve ( mean ± SD ) up to 4 hours ( n = 20 , 273.3 ± 110.0 compared with 503.3 ± 296.7 pg . hour/mL , respectively ; P = .033 ) and up to 6 hours ( n = 10 , 300.0 ± 103.3 compared with 956.7 ± 541.7 pg . hour/mL , respectively ; P = .029 ) . The extent of absorption was highly variable among subjects in each group . Conclusion There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and oral routes that may explain the difference observed in clinical efficacy . Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma , our observation of the prolonged serum concentrations in the vaginal group suggests that vaginal administration could be dosed at longer intervals than oral OBJECTIVE To identify ultrasound measurements that are the best predictors of the presence of retained products of conception ( RPOC ) within the uterine cavity in women with clinical diagnosis of incomplete miscarriage . METHODS This was a prospect i ve observational study , set in a dedicated early pregnancy assessment unit in a London teaching hospital . Endometrial thickness and the volume of suspected retained products of conception were measured by transvaginal ultrasound scan preoperatively . Indications for surgical intervention were heavy vaginal bleeding or continuous bleeding lasting > 7 days . The main outcome measure was histological evidence of chorionic villi in surgical specimens . RESULTS Among the patients , 109 ( 85 % ) had evidence of chorionic villi on histology , whilst decidua was only found in the remaining 19 ( 15 % ) . There was no identifiable cut-off for endometrial thickness or volume that could be used to differentiate between retained products of conception and decidua . CONCLUSION Measurements of endometrial thickness or volume on ultrasound scan are not good tests for diagnosing an incomplete miscarriage We evaluated the efficacy of initiating a second trimester medical abortion outside of a health care facility using patient self-administered serial intravaginal misoprostol . Patients scheduled for second trimester medical termination of pregnancy were r and omized to an inpatient or outpatient group . Both groups received a single 200-microg vaginal misoprostol tablet every 6 h. No other abortifacients were used . The home group self-administered the misoprostol and returned to the hospital for clinical reasons or after 24 h and again at 48 h. Forty-two women were assigned to the inpatient and 45 to the outpatient groups . There was no difference between the groups in demographics or indications for terminations . The median hours from first misoprostol to delivery of the fetus was 12 and 14 ( inpatient versus outpatient , respectively ; p = 0.28 ) . The total median hours in hospital were 24 versus 11 ( inpatient versus outpatient , respectively ; p < 0.05 ) . Two patients ( 4 % ) in the outpatient group delivered the fetus outside of the hospital . There were no cases of hemorrhage in either group . Outpatient initiation of second trimester medical termination with self-administered misoprostol is effective and decreases time of hospitalization |
11,209 | 17,054,149 | For the comparison with typical drugs , limited data suggest that zotepine may be as effective as these older medications .
Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs .
Trials have not highlighted clear differences between zotepine and other atypical drugs .
Zotepine may be a valuable addition to the class of atypical antipsychotic drugs . | BACKGROUND Zotepine is a relatively new antipsychotic often used for the treatment of people with schizophrenia .
It is cl aim ed to be particularly effective for negative symptoms .
OBJECTIVES To determine the effects of zotepine compared with placebo , typical and other atypical antipsychotic drugs for schizophrenia and related psychoses . | The atypical antipsychotic zotepine was compared to haloperidol in 126 patients suffering from acute exacerbation of schizophrenia ( DSM-III-R ) in a r and omized , double-blind study . After 8-weeks , 150 to 300 mg zotepine improved scores on the Brief Psychiatric Rating Scale ( BPRS ) more than 10 to 20 mg haloperidol ( -17.03 versus -13.45 ; 95%CI for zotepine-haloperidol -9.34/2.04 ) . BPRS subscores and Clinical Global impressions ( CGI ) Severity and improvement subscales showed comparable gains , but scores on the Scale for the Assessment of Negative Symptoms ( SANS ) improved significantly more with zotepine ( -23.82 ) than haloperidol ( -15.15 ; P < .05 ; 95%CI for zotepine haloperidol -18.03/-0.18 ) . Adverse events were reported by 71 percent of zotepine and 78 percent of haloperidol patients . Extrapyramidal side effect ( EPMS ) scores decreased with zotepine ( -0.34 ) but increased with haloperidol ( + 2.32 ; P < .05 ) . Seven haloperidol patients reported akathisia but no zotepine patients did ( p < .05 ) . Uric acid reductions ( which appear to have no clinical consequence ) and transient raised liver enzymes were recorded with zotepine . Weight increased on zotepine ( 2.32 kg ; P < .001 ) and a small increase in pulse rate occurred ( P < .05 ) . Both drugs were effective in reducing positive symptoms of schizophrenia ; zotepine was significantly more effective against negative symptoms and reduced EPMS 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 Several studies reported specific effects for atypical neuroleptics ( e.g. clozapine and risperidone ) in managing schizophrenic patients with aggression ( Volavka et al. , 1993 ; Chiles et al. , 1994 ; Czobor et al. , 1995 ) . There are no studies comparing different atypicals with regard to hostility . The main research question of this study was whether there are differential effects on hostility between the three atypical antipsychotics zotepine , olanzapine and risperidone . The data were collected in an open-label , r and omized , acute-phase trial . Patients were r and omized according to a fixed protocol on either olanzapine , zotepine , or risperidone after a washout period of at least 3 days . Patients did not receive any concommitant neuroleptic or antidepressant agents , while the occasional administration of benzodiazepines was allowed . Dosage range at discharge was as follows : olanzapine ( 2.5–20 mg ; mean : 11.88 ( SD : 5.94 ) ) , zotepine ( 50–275 mg ; mean : 152.27 ( SD : 76.20 ) ) , risperidone ( 1–8 mg ; mean : 3.88 ( SD:1.45 ) ) . Psychopathology was assessed at admission and discharge using the Positive and Negative Syndrome Scale ( PANSS ; Kay et al. , 1987 ) . We assessed effects on hostility and the hostile excitement syndrome ( Mass et al. , 2000 ) , which includes the PANSS-items excitement , gr and iosity , hostility , tension , mannerisms and posturing , uncooperativeness and poor impulse control . Sedation was measured with the UKU-side effect rating scale ( Lingjaerde et al. , 1987 ) . Statistical analyses had three principle objectives : ( 1 ) to assess whether there were significant changes in hostility and the hostile excitement syndrome during treatment ; ( 2 ) to test whether there were different changes in the three groups ; ( 3 ) whether these changes were not exclusively mediated by sedation or effects on positive symptoms . Sixty-nine patients fulfilling ICD-10 criteria of schizophrenia or schizoaffective-disorder participated in the study . One-way analyses of variance ( ANOVA ) revealed that all three sample s did not differ regarding age ( F = 1.84 ; NS ) , gender distribution ( m = 1.06 ; NS ) , number of cases with first episode psychosis ( m = 2.55 ; NS ) , duration of current treatment ( F = 1.79 ; NS ) and school ( F = 0.56 ; NS ) . The baseline severity of hostility of the whole group showed a range between 1 ( absent ) and 6 ( severe ) with a mean of 2.00 ( SD : 1.28 ) ) and showed no significant differences between the three subgroups ( F = 0.51 ; NS ) . Also excitement ( F = 0.35 ; NS ) , gr and iosity ( F = 0.18 ; NS ) , tension ( F = 0.43 ; NS ) , mannerisms and posturing ( F = 0.76 ; NS ) , uncooperativeness ( F = 0.63 ; NS ) and poor impulse control ( F = 0.61 ; NS ) showed no differences between the three groups at baseline . ( Table 1 ) . Paired t-tests ( admission vs. discharge ) were conducted separately for all three groups : patients Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease . While clozapine has been shown to be effective in this respect , no data are available on zotepine . We report on a double-blind r and omized study design ed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia . Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity . Passage time , route , and motor errors were evaluated . 25 schizophrenic ( DSM-IIIR ) patients were included in each group . After washout , they were r and omized on zotepine or clozapine and given up to 450 mg of substance each . Patients were followed for six weeks and evaluated weekly . We report on a sub sample of 26 patients matched for baseline BPRS , SANS , and age . 13 matched healthy persons were recruited as controls . ANOVA with group and course over time as factors was used for analysis . Both clozapine and zotepine achieved a highly significant decrease in overall symptoms ( BPRS ) and negative symptoms ( SANS ) . Zotepine and clozapine were equally effective . In the maze tests , motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a " trait " marker . In passage time and maze route , schizophrenics performed worse than controls . An improvement by medication was evident in both medication groups , but was more pronounced in the zotepine-treated group . The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia . The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction , confirming this substance 's value as an atypical antipsychotic & NA ; Zotepine , a neuroleptic agent with additional 5‐HT2 blocking properties , was compared with haloperidol in the treatment of schizophrenic patients with predominantly negative symptoms using a double‐blind design . During the investigation period zotepine treated patients showed significant improvements in all rating instruments whereas haloperidol treated patients did not . Patients in the zotepine group developed fewer clinical side effects . The results of the presented study confirm the positive impressions gained in earlier open trials with zotepine Abstract . Rationale : Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia . Antipsychotic drugs also require to be effective in prevention of recurrence . Objective : This trial was design ed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia . Methods : The study was a double-blind , parallel group , 26-week comparison of zotepine ( 300 mg daily , with fall back to 150 mg if necessary ) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months . The primary outcome measure was the time to recurrence . Other evaluations included the brief psychiatric rating scale ( BPRS ) , the scale for the assessment of negative symptoms ( SANS ) , the clinical global impression ( CGI ) severity and improvement scales , and the Simpson and Angus scale for extrapyramidal symptoms ( EPS ) . Results : Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients ( 4 versus 21 , respectively ) . The estimated 26-week risk of recurrence was six times lower for zotepine than placebo ( 8.7 % versus 52.8 % ; hazard ratio 0.16 , 95 % CI 0.053 , 0.484 ; P<0.001 ) . Scores on the BPRS and CGI supported the efficacy of zotepine . There was no difference between the treatments with respect to EPS . Conclusions : Zotepine is effective in preventing recurrence in patients with chronic schizophrenia . The level of EPS was not different between zotepine and placebo Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial . Using overall improvement ratings and Gorham 's BPRS , zotepine rated higher improvement in motor retardation , suspiciousness , mannerisms and posturing symptoms , suggesting that it has both activating and antipsychotic activities . Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior , somatic concerns , anxiety , guilt feelings , tension , depressive mood and uncooperativeness . As for side effects , there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene . The lower incidence of insomnia is interesting in view of zotepine 's clinical activating effects . There were no abnormal laboratory findings Zotepine , a neuroleptic exercising a 5-HT2-antagonistic effect , was employed in a double-blind study in the treatment of schizophrenic patients with predominantly negative symptoms and was compared to haloperidol . In contrast to the patients treated with haloperidol , significant improvements were seen in the zotepine group during the observation period , according to all assessment scales that were employed . The patients of the zotepine group also developed fewer clinical side effects . The results of the study confirm previous positive impressions gained in earlier open studies with zotepine Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration The clinical action of Zotepine was examined in an open and in a r and omised double-blind controlled study in in- patients displaying a productive or minus pattern of symptoms within the framework of a schizophrenic disease or schizoaffective psychosis . The present paper discusses only the results achieved in treating schizophrenic minus patterns of signs and symptoms . In Study I 20 schizophrenic patients were treated with two different Zotepine dosages . Group 2 ( n = 12 ) showed at an average daily dose of 168 + /- 15 mg ( 150 - 190 mg ) a significant improvement ( p less than 0.05 ) of the anergy subscore in the BPRS scale as well as a significant improvement of the subscores affective flattening , anhedonia/asociality and attentional imparvement in the SANS scale , compared with Group 1 ( n = 8) with an average daily dose of 270 + /- 37 mg ( 240 - 340 mg ) . This improvement developed already during the first two weeks of the treatment . In Study II the antipsychotic action of Zotepine compared to that of perazine was studied under double-blind conditions . The average daily dose in the Zotepine group ( n = 20 ) was around 241 + /- 70 mg ( 106 - 396 mg ) , in the perazin group ( n = 19 ) at 348 + /- 09 mg ( 214 - 575 mg ) . With regard to the BPRS subscore anergy and all the subscores of the SANS scale , there was a distinct improvement without significant group differences . Both substances were comparably well tolerated BACKGROUND In contrast to traditional antipsychotic medication , newer , the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both , acute and chronic schizophrenia and improve quality of life . Zotepine , a D (2)5HT ( 2A ) antagonist , was compared to placebo in this clinical trial to address these issues . METHODS In an adaptive , 8-week multicenter , double-blind , r and omized , parallel group study , efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients ( 53 % males , age 41 + /- 11 years ) who experienced stable primary negative symptoms . Efficacy was assessed using the PANSS ( primary outcome criterion : PANSS negative score ) , CGI , and MADRS ; safety was controlled by EPS ( Simpson-Angus Scale ) , TDRS and adverse events . Quality of life was evaluated with the SF-36 health question naire . RESULTS After eight weeks of treatment with an average dose of 131 + /- 49 mg/day of zotepine , no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale " negative symptoms could be demonstrated . Although patients receiving zotepine showed a pronounced reduction ( per protocol set : -7.8 + /- 5.8 ) during treatment , it was not statistically different from a marked placebo response ( -6.5 + /- 5.8 ) . Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS , the CGI and the MADRS . With regards to the quality of life assessment , patients under zotepine showed better results in the physical component scale and psychological well-being scale . In general , zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo . CONCLUSIONS Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial . The main reasons for this finding were a high placebo response in a selected population , a probably too low dose of zotepine , and a short study period . However , several findings show clinical benefit of zotepine therapy in efficacy and quality of life The efficacy and tolerance of zotepine and haloperidol were examined in 40 patients suffering from paranoid schizophrenia ( DSM III ) . The study period was 6 weeks . Psychopathology was assessed with BPRS and CGI . Documentation of side effects was done with DOTES . The safety parameters were pulse , blood pressure , leucocyte count , liver enzymes , ECG and EEG , determined at different times . Both treatment groups improved significantly without any differences in respect to efficacy . The patients who had been treated with zotepine had significantly fewer extrapyramidal side effects . However , transient increases in liver enzyme levels were seen more frequently in the zotepine group . There were no differences between the groups in respect to other side effects To assess the efficiency/risk ratio , fixed doses of zotepine and haloperidol were compared by means of a double-blind study in acute schizophrenics over a 4-week period . The assessment tools were BPRS , CGI , and the Simpson-Angus scale for the extrapyramidal disturbances , and a free report on side effects . No differences between the groups were found in respect of efficacy . According to the Simpson-Angus scale , the patients who had been treated with zotepine achieved better values , this being a general trend . There were significant differences according to the free report on side effects . Especially at onset of treatment , the patients treated with zotepine complained of tiredness . Partly marked extrapyramidal disturbances were seen in the patients who had been treated with haloperidol A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors Zotepine was administered to 45 patients suffering from therapy-resistant psychoses hospitalized in eight psychiatric institutes ( University Hospital Okayama and affiliated institutions ) . The psychoses of these patients were characterised by positive symptoms -- predominantly hallucinations and delusions-- and could not be influenced by a large variety of conventional antipsychotics , such as haloperidol . Previous medications were discontinued or administered together with zotepine . To assess changes in the pattern of symptoms , the Brief Psychiatric Rating Scale ( BPRS ) was employed over a period of up to 12 weeks at 2-week intervals . Ten patients dropped out of the study because of undesirable effects or for other reasons . 35 patients completed the 12-week study according to schedule . There was a relation between general improvement and certain patient characteristics . Zotepine proved to be effective especially in the catatonic type of schizophrenia , in chronic schizophrenias with acute exacerbation ( DSM-III ) and in relatively young patients in whom the disease had existed for a short time only . In the 26 patients who were markedly , moderately or slightly improved , BPRS score had dropped significantly after only two weeks of treatment . This points to a rapid onset of the therapeutic action of zotepine Objective : The aim was to evaluate the efficacy of zotepine in the treatment of acute episodes of schizophrenia In a double-blind , placebo-controlled study the encephalotropic and psychotropic properties of zotepine - a new tricyclic dibenzothiepine with antidopaminergic , adrenolytic and antiserotoninergic properties - were investigated utilizing quantitative EEG , psychometric and psychophysiological tests as well as clinical observations . Fifteen normal volunteers received r and omized ( latin square design ) and at weekly intervals single oral doses of placebo , 25 mg , 50 mg and 100 mg zotepine as well as 50 mg clozapine as reference compound . Plasma samplings for blood levels , EEG recordings , and evaluation of blood pressure , pulse rate and side-effects were carried out at the hours 0 , 1 , 2 , 4 , 6 and 8 , while psychometric data were recorded at the same time except the first hour . Computer-assisted spectral analysis of the EEG demonstrated after all three doses significant changes as compared with placebo characterized by an augmentation of delta and theta activity , decreased of alpha and beta activity , slowing of the centroid of the total activity and alpha activity , and decrease of the dominant frequency and its absolute and relative power . Such changes are typical for low-potency basic neuroleptics of the sedative type such as chlorpromazine . Clozapine also augmented slow activities , decreased alpha activity , the dominant frequency and the alpha centroid , but induced in contrast to zotepine a concomitant increase of fast beta activity , acceleration of the beta centroid and no slowing of the dominant frequency , while the total power was significantly attenuated . These findings confirm earlier reports about the pharmaco-EEG profile of clozapine , which has a resemblance to profiles of anticholinergic antidepressants of the amitriptyline type . Psychometric tests demonstrated after the higher doses of zotepine and clozapine a deterioration of noopsychic and thymospsychic functions which was more pronounced after the reference compound than after zotepine . The lowest dose of zotepine , 25 mg , even produced an improvement in numerical memory and complex reaction . CFF , skin conductance , pupillary diameter and pupillary response measurements decreased after both compounds . Dose-efficacy calculations showed 100 mg zotepine and clozapine to be the most CNS-effective compounds , followed by 50 mg and 25 mg zotepine , while placebo induced the least changes . Time-efficacy calculations showed neurophysiological and behavioral peak effects after zotepine at the 4th and 6th hour , as compared with the 2nd and 4th hour after clozapine . Pulse rate increased with both compounds ; blood pressure decreased after clozapine but remained unchanged after zotepine . ( ABSTRACT TRUNCATED AT 400 WORDS |
11,210 | 18,248,702 | Our results support the economic viability of a national screening program for men reaching 65 years of age in Canada . | OBJECTIVE Recently generated r and omized screening trial data have provided good evidence in favour of routine screening for abdominal aortic aneurysm ( AAA ) to reduce AAA-related deaths in men aged 65 years and older .
We developed an economic model that assessed the incremental cost-utility of AAA screening to help decision makers judge the relevance of a national screening program in Canada . | PURPOSE Although early death from perioperative myocardial infa rct ion ( PMI ) after vascular surgery is well established , long-term outcome in patients surviving PMI is unknown . This prospect i ve study was design ed to determine cardiac outcome and survival rates in patients with symptomatic and asymptomatic nonfatal PMI associated with peripheral vascular surgery . METHODS During a 36-month period for 1989 to 1992 , all patients undergoing vascular surgery at our institution were monitored for PMI with serial creatine kinase and myocardial b and isoenzymes and electrocardiography . PMIs were classified as symptomatic ( associated with chest pain , arrhythmia , congestive heart failure , or hypotension ) or asymptomatic ( electrocardiographic changes and /or elevated creatine kinase and myocardial b and isoenzymes ) . Patients with PMI were then prospect ively monitored and compared for late survival , with control patients undergoing vascular surgery without PMI during the same interval . RESULTS During the study period 1561 major peripheral vascular procedures were performed . There were 47 PMIs ( 3.0 % ) . Eleven ( 0.7 % ) PMIs were fatal , 31 were nonfatal , and five other patients with PMI died during operation of non-heart-related causes . Eight of 31 patients with nonfatal PMI had a " chemical PMI " with creatine kinase and myocardial b and isoenzyme elevation as the sole indicator of PMI . During follow-up ( mean 27.7 months ) , there was a higher incidence of both subsequent myocardial infa rct ion and coronary artery revascularization among the patients with nonfatal PMI compared with control subjects ( p < 0.05 ) ; however , survival for patients with nonfatal PMI at 1 and 4 years ( 80 % and 51 % ) did not differ from that of control patients ( 90 % and 60 % ) ( p > 0.05 ) . Patients with " chemical PMI " had similar patterns of subsequent myocardial infa rct ion and coronary intervention as control patients . CONCLUSIONS Patients surviving nonfatal PMI after peripheral vascular surgery have a higher incidence of subsequent adverse cardiac events and coronary artery revascularization than patients undergoing vascular surgery without PMI , but they have similar survival rates at 1 and 4 years . Patients in the enzyme-only PMI group have a similar outcome compared with control subjects suggesting that a perioperative " chemical MI " may not be a significant clinical event This article describes the patient population and operative management of 666 patients with nonruptured aneurysms of the abdominal aorta . Statistical significance of variables was determined by the chi-square test and logistic regression analysis . There were no statistically significant differences ( p greater than 0.05 ) in mortality rate for abdominal aortic aneurysm ( AAA ) on the basis of indication for surgery ( asymptomatic , 3.9 % ; asymptomatic but with evidence of enlargement , 4.9 % ; and symptomatic , 7.2 % ) or the urgency of operation ( elective operation , 4.5 % ; and urgent operation , 7.1 % ) . Characteristics of the 72 participating surgeons did not influence the operative mortality rate . A family history of AAA was documented in 6.1 % of cases and was more common if the patient was female ( p = 0.03 ) and less than 65 years of age ( p = 0.04 ) . Patients without clinical evidence of coronary artery disease had a 0.8 % mortality rate from cardiac disease compared with 6.2 % if any stigmata of coronary disease were present . Prior aortocoronary bypass surgery did not reduce the incidence of postoperative cardiac events or operative mortality rate . Patients having " routine " angiography did not have a less complicated operative course , fewer thrombotic complications , or lower mortality rate than those not having it . Those patients with an inflammatory AAA ( 4.5 % ) did not have a significantly higher incidence of pain . Heparin administration ( 84.8 % ) did not reduce the complications of graft thrombosis , " trash , " distal thrombosis , and /or amputation . The 6.8 % of patients requiring suprarenal aortic cross-clamping had a higher incidence of postoperative renal dysfunction ( p = 0.02 ) and intraoperative blood loss ( p less than 0.001 ) , but cardiac events were not more frequent . When the aortic cross-clamping time was prolonged ( more than 70 minutes ) , the requirement for crystalloid fluid administration increased ( p less than 0.001 ) and postoperative myocardial infa rct ion was more common ( p = 0.004 ) . After ligation of the left renal vein in 7.9 % , renal damage or dialysis was more frequent ( p = 0.01 ) . Patients having an intra-abdominal graft ( tube , 38.5 % and biiliac , 30.7 % ) had fewer wound infections ( p = 0.02 ) and graft thromboses ( p less than 0.001 ) than the patients with a femoral anastomosis . When the internal iliac artery flow was interrupted bilaterally ( 12 % ) , diarrhea ( p = 0.03 ) and ischemic colitis ( p = 0.03 ) were more frequent complications . Reimplantation of the inferior mesenteric artery was carried out in 4.8 % . After renal artery bypass in 2.1 % , the mortality rate was not increased , but the incidence of transient renal dysfunction was increased ( p = 0.03 ) . ( ABSTRACT TRUNCATED AT 400 WORDS Physicians must make decisions about screening patients for abdominal aortic aneurysms ( AAAs ) , monitoring or referring for surgery patients with AAAs of various sizes , and assessing patients with symptoms that may be related to AAAs . This review article analyzes the evidence for each scenario . The effectiveness and cost-effectiveness of screening for AAA is based on results from four r and omized controlled trials . A cost-effectiveness analysis using a Markov model showed that ultrasound screening of white men beginning at age 65 is both effective and cost-effective in preventing AAA-related death . Such screening would have a small but real impact over a 20-year period in these men . For patients with a known AAA — which is often detected incidentally — the evidence clearly suggests periodic ultrasound surveillance for those with small AAAs ( 3.0–3.9 cm in diameter ) and elective surgical repair for those with large AAAs ( = 5.5 cm ) . Two recent r and omized controlled trials have shown that early surgical repair confers no survival benefit compared with periodic surveillance for patients with intermediate-sized AAAs ( 4.0–5.5 cm in diameter ) , so those patients can also be monitored . Some centers choose to increase the frequency of monitoring to every 3 to 6 months when the AAA reaches 5.0 cm . Factors to consider in assessing symptomatic patients include the high risk of life-threatening conditions , the potential increased risk of death or poor outcome with delay in diagnosis , the limitations of ultrasound in identifying whether symptoms are due to known or suspected AAA , and the timely availability of computed tomography or other imaging tests . If available , computed tomography is preferred in patients with recent or severe symptoms , since it is better at detecting retroperitoneal hemorrhage and other complications and in providing preoperative definition of the anatomy CONTEXT Among patients with abdominal aortic aneurysm ( AAA ) who have high operative risk , repair is usually deferred until the AAA reaches a diameter at which rupture risk is thought to outweigh operative risk , but few data exist on rupture risk of large AAA . OBJECTIVE To determine the incidence of rupture in patients with large AAA . DESIGN AND SETTING Prospect i ve cohort study in 47 Veterans Affairs medical centers . PATIENTS Veterans ( n = 198 ) with AAA of at least 5.5 cm for whom elective AAA repair was not planned because of medical contraindication or patient refusal . Patients were enrolled between April 1995 and April 2000 and followed up through July 2000 ( mean , 1.52 years ) . MAIN OUTCOME MEASURE Incidence of AAA rupture by strata of initial and attained diameter . RESULTS Outcome ascertainment was complete for all patients . There were 112 deaths ( 57 % ) and the autopsy rate was 46 % . Forty-five patients had probable AAA rupture . The 1-year incidence of probable rupture by initial AAA diameter was 9.4 % for AAA of 5.5 to 5.9 cm , 10.2 % for AAA of 6.0 to 6.9 cm ( 19.1 % for the subgroup of 6.5 - 6.9 cm ) , and 32.5 % for AAA of 7.0 cm or more . Much of the increased risk of rupture associated with initial AAA diameters of 6.5 - 7.9 cm was related to the likelihood that the AAA diameter would reach 8.0 cm during follow-up , after which 25.7 % ruptured within 6 months . CONCLUSION The rupture rate is substantial in high-operative-risk patients with AAA of at least 5.5 cm in diameter and increases with larger diameter PURPOSE We present extended follow-up findings of the Kingston prospect i ve sizing program for patients with abdominal aortic aneurysm ( AAA ) smaller than 5.0 cm in diameter , with gender-specific analysis . METHODS From 1976 to 2001 , 895 patients ( 688 men , 207 women ) with AAA smaller than 5.0 cm were entered , regardless of fitness , in a prospect i ve sizing program in which computed tomography scans were obtained every 6 months . Operations were performed in fit patients with an increase in AAA size to 5 cm ( n = 190 ) , AAA expansion greater than 0.5 cm in 6 months ( n = 27 ) , or for other reasons ( n = 33 ) . Follow-up continued until AAA rupture , surgery , death , or removal from the program . RESULTS No AAA smaller than 5.0 cm ruptured during prospect i ve follow-up . There was a statistically significant increase in expansion rate relative to size at entry , with the highest mean expansion rate of 0.52 cm/y for AAA 4.5 to 4.9 cm in diameter . There was no significant difference in AAA expansion rate between men and women . The frequency of surgery was inversely related to age at entry , but was positively related to AAA size at entry , with patients with AAA 4.5 to 4.9 cm at entry 6.8 times more likely ( 95 % confidence interval , 4.3 - 10.7 ) to undergo surgery than those with AAA 3.0 to 3.4 cm at entry . Women were older than men at entry , and age at entry in those undergoing surgery was significantly greater in women . CONCLUSIONS The study confirms the results of the United Kingdom Small Aneurysm Trial and the Aneurysm Detection and Management Study , that is , that risk for rupture is extremely unlikely with AAA smaller than 5.0 cm , which enables safe follow-up surveillance programs in both men and women with AAA smaller than 5.0 cm Gloucestershire 's screening project shows the potential benefits of a national programme and how it could be run Every year about 6000 men die from a ruptured abdominal aortic aneurysm in Engl and and Wales.1 Although this represents only about 2 % of all deaths in men , the condition is largely preventable . It is also a disease that seems to be increasingly prevalent , at least in Scotl and , despite the fact that deaths from other atherosclerotic conditions are reducing.2 This article explores the requirements for a national aortic screening programme , using as a model the Gloucestershire aneurysm screening project , which has been running for 13 years.3 Ultrasound screening for abdominal aortic aneurysms fulfils all the criteria for a population screening programme,4 5although only in men.6 The recent multicentre aneurysm screening study found that screening reduced the mortality from aneurysm disease in men by 42 % after four years of follow up ; it is expected , with further study , to show a small but significant decrease in the population mortality.7 The study also showed that screening is as cost effective as other current screening programmes , at a cost of £ 28 000 for each added year of life.8 ! [ ] [ 1 ] Ruptured abdominal aortic aneurysm is largely preventable Credit : GCa/SPL This information builds on data from previous smaller r and omised studies , 9–11 and has encouraged debate about the value of a national screening programme for aortic aneurysms.12 13 The National Screening Committee in the United Kingdom is currently assessing the evidence before making any recommendation .14 Our experience in Gloucestershire shows how a screening programme could work . Screening for abdominal aortic aneurysm was introduced in Gloucestershire in September 1990 . All men reaching the age of 65 who are registered with general practice s in the county are offered an ultrasound scan of … [ 1 ] : Background and Purpose — Very few studies have provided information regarding long-term prognosis after stroke . We aim ed to determine the absolute and relative survival over 10 years among patients with first-ever stroke from a population -based study in Perth , Western Australia . Methods — For a 12-month period beginning February 1989 , all individuals with a suspected acute stroke or transient ischemic attack who were resident in a geographically defined and representative region of Perth , Western Australia , were registered prospect ively and assessed according to st and ardized diagnostic criteria . Patients with a definite first-ever stroke were followed up prospect ively at 4 months , 12 months , 5 years , and 10 years after the index event . Results — A total of 251 patients with first-ever stroke were registered , and 244 ( 97 % ) were followed up at 10 years , by which time 197 ( 79 % ; 95 % confidence interval [ CI ] , 74 to 84 ) had died . The major causes of death were the direct effects of the initial stroke ( 27 % ; 95 % CI , 21 to 33 ) and cardiovascular disease ( 26 % ; 95 % CI , 20 to 32 ) . Among 1-year survivors of stroke , the average annual case fatality was 4.8 % , which was 2.3 ( 95 % CI , 1.9 to 2.7 ) times greater than for the general population of the same age and sex . Conclusions — One in 5 patients with first-ever stroke survived to 10 years . The average annual case fatality was 4.8 % between years 1 and 10 after stroke , which was twice that expected for the general population . Vascular disease is the major cause of death among long-term survivors of stroke Screening for abdominal aortic aneurysm ( AAA ) is commonly restricted to men . Recent studies have indicated a possible increase in deaths due to ruptured AAA in women , and a higher rate of rupture in women than in men . The present report details results from a r and omized controlled trial that assessed the effects of screening women for AAA PURPOSE On the basis of a prospect i ve analysis of 147 patients undergoing surgery for ruptured abdominal aortic aneurysm ( AAA ) and recorded in the Canadian Society for Vascular Surgery Aneurysm Registry , this study defines the early and 6-year actuarial survival rates and determines the predictive variables that are associated with survival . METHODS Ongoing follow-up of a cohort of patients was current at the time of analysis . To identify the preoperative , intraoperative , and postoperative variables that were associated with survival , statistical methods included chi-squared analysis , logistic regression analysis , Kaplan-Meier analysis , and Cox regression analysis . RESULTS The survival rate was 48.6 % at 1 month , 34.7 % + /- 4.2 % at 3 years , and 22.0 % + /- 4.0 % at 6 years . When preoperative and intraoperative variables were considered and logistic regression analysis was used , the highest probability of early in-hospital survival was associated with preoperative creatinine levels of 1.3 mg/dl or less , intraoperative urine output of 200 ml or greater , and infrarenal clamp site . The highest probability of late survival , as calculated by the Cox proportional hazards method , was predicted by the patient 's age and total urine output during the procedure . When all variables , including postoperative complications , were considered , late survival was highest if intraoperative urine output was 200 ml or greater and respiratory failure and myocardial infa rct ion did not occur . For those patients with ruptured AAA who survived operation ( i.e. , greater than 1 month ) , the long-term survival rate was significantly lower than a comparable group undergoing repair of nonruptured AAA . CONCLUSIONS Patients who survive repair of a ruptured AAA have a lower late survival rate than patients undergoing elective repair . When a patient is evaluated before operation , no combination of preoperative variables could identify those patients with little or no chance of survival ; hence , the decision to repair a ruptured AAA should be made on clinical grounds . However , after surgery ( when information on intraoperative and postoperative variables is also available ) , the results of this study provide a basis for the surgeon to use these prognostic variables to assist clinical judgment and guide discussion s on prognosis with the family and to identify those patients who have such a low chance of early and late survival that further aggressive treatment may be futile BACKGROUND Although the initial results of endovascular repair of abdominal aortic aneurysms were promising , current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair . METHODS We conducted a multicenter , r and omized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable c and i date s for both techniques . The outcome events analyzed were operative ( 30-day ) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications . RESULTS The operative mortality rate was 4.6 percent in the open-repair group ( 8 of 174 patients ; 95 percent confidence interval , 2.0 to 8.9 percent ) and 1.2 percent in the endovascular-repair group ( 2 of 171 patients ; 95 percent confidence interval , 0.1 to 4.2 percent ) , result ing in a risk ratio of 3.9 ( 95 percent confidence interval , 0.9 to 32.9 ) . The combined rate of operative mortality and severe complications was 9.8 percent in the open-repair group ( 17 of 174 patients ; 95 percent confidence interval , 5.8 to 15.2 percent ) and 4.7 percent in the endovascular-repair group ( 8 of 171 patients ; 95 percent confidence interval , 2.0 to 9.0 percent ) , result ing in a risk ratio of 2.1 ( 95 percent confidence interval , 0.9 to 5.4 ) . CONCLUSIONS On the basis of the overall results of this trial , endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter . Long-term follow-up is needed to determine whether this advantage is sustained BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms During a recent 30-month period , we repaired 10 ruptured abdominal aortic aneurysms ( RAAA ) at our institution . To evaluate the survival , postoperative morbidity , and financial impact of treating RAAA , we compared these patients with 10 r and omly selected patients undergoing elective AAA ( EAAA ) . Both groups were comparable for age , gender , and incidence of diabetes , hypertension , coronary artery disease , chronic obstructive pulmonary disease ( COPD ) , and renal failure . Although we have noted a dramatic increase in survival for RAAA ( 90 % ) , the morbidity continues to be unacceptably high ( 60 % ) . Efforts should be made toward better detection of AAA prior to rupture as well as development of strategies to minimize or prevent these major complications . Potential average savings accrued from one patient undergoing EAAA repair rather than RAAA repair ( $ 93,139 . 21 ) can be used to perform screening abdominal ultrasound tests in patients at increased risk of having an AAA Objectives To compare attendance and prevalence of abdominal aortic aneurysm ( AAA ) in population based r and omised trials of sonographic screening in the United Kingdom , Western Australia , and Denmark . Methods 65 290 men were r and omised to screening in the four trials , and data were collected and analysed from 46 397 aortic scans for men aged between 64 and 83 years who attended one of four community screening programmes . Comparisons were made for age st and ardised population s ( 65–74 years ) . Results Age st and ardised attendance varied between 74 % and 81 % , and was highest in the United Kingdom and lowest in Western Australia . Age st and ardised prevalence of AAAs of 3.0 cm or more varied significantly between 4.5 % and 7.7 % , and was highest in the United Kingdom and lowest in Denmark . Conclusions Participation in the four programmes compares favourably with other reported screening studies . The possibility that variations may reflect the different recruitment methods used is discussed . The prevalence of AAA in central Denmark would appear to be significantly different from that in southern Engl and and Western Australia The study was an up date at 10 years of a r and omized trial of the efficacy of screening for abdominal aortic aneurysm ( AAA ) . The extent of benefit , feasibility and compliance were examined , and reasons why this intervention may fail a proportion of those screened were identified BACKGROUND Little is known about the rate at which new abdominal aortic aneurysms ( AAAs ) develop or whether screening older men for AAA , if undertaken , should be limited to once in a lifetime or repeated at intervals . METHODS A large population of veterans , aged 50 through 79 years , completed a question naire and underwent ultrasound screening for AAA . Of these , 5151 without AAA on the initial ultrasound ( defined as infrarenal aortic diameter of 3.0 cm or larger ) were selected r and omly to be invited for a second ultrasound screening after an interval of 4 years . Local records and national data bases were search ed to identify deaths and AAA diagnoses made during the study interval in subjects who did not attend the rescreening . RESULTS Of the 5151 subjects selected for a second screening , 598 ( 11.6 % ) had died ( none due to AAA ) , and 20 ( 0.4 % ) had an interim diagnosis of AAA . A second screening was performed on 2622 ( 50.9 % ) , of whom 58 ( 2.2 % ; 95 % confidence interval , 1.6%-2.8 % ) had new AAA . Three new AAAs were 4.0 to 4.9 cm , 10 were 3.5 to 3.9 cm , and 45 were 3.0 to 3.4 cm . Independent predictors of new AAA at the second screening included current smoker ( odds ratio , 3.09 ; 95 % confidence , 1.74 - 5.50 ) , coronary artery disease ( odds ratio , 1.81 ; 95 % confidence interval , 1.07 - 3.07 ) , and , in a separate model using a composite variable , any atherosclerosis ( odds ratio , 1.97 ; 95 % confidence interval , 1.16 - 3.35 ) . Adding the interim and rescreening diagnosis rates suggests a 4-year incidence rate of 2.6 % . Rescreening only in subjects with infrarenal aortic diameter of 2.5 cm or greater on the initial ultrasound would have missed more than two thirds of the new AAAs . CONCLUSIONS A second screening is of little practical value after 4 years , mainly because the AAAs detected are small . However , the incidence that we observed suggests that a second screening after longer intervals ( ie , more than 8 years ) may provide yields similar to those seen in initial screening and therefore warrants further study The management of small abdominal aortic aneurysms less than 5.0 cm maximum diameter remains controversial particularly in patients who are medically fit . All patients referred with abdominal aortic aneurysms less than 5.0 cm maximum diameter were prospect ively followed regardless of their fitness for operation . Two hundred sixty-eight patients had been entered into the study by December 31 , 1988 , and monitored until December 31 , 1990 , by at least two aneurysm sizings by ultrasonography , CT scanning , or both . The mean follow-up was 42 months . Operations were performed on 114 patients ( if they were fit for operation ) when the aneurysm reached 5.0 cm , exp and ed more than 0.5 cm in a 6-month period , or when the patient had significant occlusive disease requiring repair . In this group the mean annual increase in diameter was 0.9 cm . One hundred fifty-four patients were monitored without operation for a mean period of 42 months . One rupture occurred in this group . The average annual increase in diameter in the group not undergoing operation was 0.24 cm . This study supports a policy of observation for abdominal aortic aneurysms less than 5.0 cm in maximum diameter OBJECTIVE To investigate risk factors associated with aneurysm rupture using patients r and omized into the U.K. Small Aneurysm Trial ( n = 1090 ) or monitored for aneurysm growth in the associated study ( n = 1167 ) . SUMMARY BACKGROUND DATA The U.K. Small Aneurysm Trial has shown that ultrasound surveillance is a safe management option for patients with small abdominal aortic aneurysms ( 4.0 to 5.5 cm in diameter ) , with an annual rupture rate of 1 % . METHODS In the cohort of 2257 patients ( 79 % male ) , aged 59 to 77 years , 103 instances of abdominal aortic aneurysm rupture were identified during the 7-year period of follow-up ( 1991 - 1998 ) . Almost all patients ( 98 % ) had initial aneurysm diameters in the range of 3 to 6 cm , and the majority of ruptures ( 76 % ) occurred in patients with aneurysms > or = 5 cm in diameter . Kaplan-Meier survival and Cox regression analysis were used to identify baseline risk factors associated with aneurysm rupture . RESULTS After 3 years , the annual rate of aneurysm rupture was 2.2 % ( 95 % confidence interval 1.7 to 2.8 ) . The risk of rupture was independently and significantly associated with female sex ( p < 0.001 ) , larger initial aneurysm diameter ( p < 0.001 ) , lower FEV1 ( p = 0.004 ) , current smoking ( p = 0.01 ) , and higher mean blood pressure ( p = 0.01 ) . Age , body mass index , serum cholesterol concentration , and ankle/brachial pressure index were not associated with an increased risk of aneurysm rupture . CONCLUSIONS Within this cohort of patients , women had a threefold higher risk of aneurysm rupture than men . Effective control of blood pressure and cessation of smoking are likely to diminish the risk of rupture OBJECTIVES to analyse the hospital costs and benefits of screening older males for abdominal aortic aneurysm ( AAA ) . MATERIAL S AND METHODS in 1994 a hospital-based screening trial of 12 658 65 - 73-year-old males was started . AAA > 5 cm were referred for surgery . The remaining AAA were offered annual scans . Those with aortic ectasia were rescreened at 5 yearly intervals . AAA-operations and hospital AAA-related deaths were research ed . The costs of screening , surveillance , and treatment were also registered . RESULTS the attendance rate was 76 % ; of whom 191 ( 4.0 % ) had AAA . Mean observation time was 5.13 years . Sixty in the screened and 41 in the control group were operated ( p=0.06 ) , of which 7 and 27 respectively were operated as an emergency ( p<0.001 ) , and 6 and 19 respectively died due to AAA ( p=0.009 ) . The costs per scan were 83.50 DKK , 81 400 DKK per emergency operation ( 71 485 DKK after screening ) , and 117 000 DKK per emergency operation . The cost per prevented hospital death was 67 855 DKK , equivalent to approximately life year saved approx . 7540 DKK ( GBP1=12 DKK ) . CONCLUSION screening appears to reduce hospital AAA mortality and to be cost-effective BACKGROUND Although several studies have shown that simulated annual direct health care costs are substantially lower for patients undergoing more frequent hemodialysis ( HD ) , there is limited information about the economics of daily HD and nocturnal HD . METHODS The London Daily/Nocturnal Hemodialysis Study compared the economics of short daily HD ( n = 10 ) , long nocturnal HD ( n = 12 ) , and conventional thrice-weekly HD ( n = 22 ) in patients over 18 months . A retrospective analysis of patients ' conventional HD costs during the 12 months before study entry was conducted to measure the change in cost after switching to quotidian HD . RESULTS As the data show , annual costs ( in Canadian dollars ) for daily HD are substantially lower than for both nocturnal HD and conventional HD : approximately 67,300 Can dollars , 74,400 Can dollars , and 72,700 Can dollars per patient , respectively . Moreover , marginal changes in operating cost per patient year were - 9,800 Can dollars , -17,400 Can dollars , and + 3,100 Can dollars for the daily HD , nocturnal HD , and conventional HD groups . Because of the increase in number of treatments , treatment supply costs per patient for the daily HD and nocturnal HD study groups were approximately twice those for conventional HD patients . However , average costs for consults , hospitalization days , emergency room visits , and laboratory tests for quotidian HD patients tended to decline after study entry . The major cost saving in home quotidian HD derived from the reduction in direct nursing time , excluding patient training . Total annualized cost per quality -adjusted life-year for the daily HD and nocturnal HD groups were 85,442 Can dollars and 120,903 Can dollars , which represented a marginal change of - 15,090 Can dollars and - 21,651 Can dollars , respectively , reflecting both improved quality of life and reduced costs for quotidian HD patients . CONCLUSION Substantial clinical benefits of home quotidian HD , combined with the economic advantage shown by this study , clearly justify its expansion OBJECTIVE To describe the potential psychological consequences of screening for abdominal aortic aneurysms ( AAAs ) . METHODS The participants were prospect ively and r and omly sample d from a r and omised screening trial for AAA and asked to complete a vali date d generic and global anonymous quality of life ( QL ) question naire by self- assessment ( ScreenQL ) . Material case-control study : ScreenQL was completed once by 168 ( 48 % ) of 350 non-responders to screening , 271 ( 81 % ) of 335 attenders before screening , 286 ( 85 % ) of 335 attenders after screening , 127 ( 85 % ) of 149 with a small AAA diagnosed at screening , and 231 ( 66 % ) of 350 who were r and omised not to be offered screening for AAA ( controls ) . Prospect i ve study ( paired data ): 127 men having a small AAA diagnosed . Twenty-nine ( 81 % ) of 36 men operated after initial conservative treatment . RESULTS Initially , the QL score was 5 % lower among men with a small AAA compared to the controls ( p<0.05 ) , mainly because of poorer health perception . The QL score declined significantly further to 7 % below control values during the period of conservative treatment . This impairment was mainly due to a 21 % and 15 % reduction in scores relating to health perception and psychosomatic distress , respectively . However , all scores improved to control levels in patients operated on . The QL of attending men for screening was significantly lower than that of the controls and the attenders after the screening . No differences were noticed concerning the non-attenders . CONCLUSION The offer of screening causes transient psychological stress in subjects found not to have AAA . However , diagnosis of an AAA seems to impair QL permanently and progressively in conservatively treated cases . This impairment seems reversible by operation . Nevertheless , the impairment seems considerable , and must be considered in the management of AAA and in the final evaluation of screening for AAA OBJECTIVE To assess whether screening for abdominal aortic aneurysms in men reduces mortality . DESIGN Population based r and omised controlled trial of ultrasound screening , with intention to treat analysis of age st and ardised mortality . SETTING Community based screening programme in Western Australia . PARTICIPANTS 41,000 men aged 65 - 83 years r and omised to intervention and control groups . INTERVENTION Invitation to ultrasound screening . MAIN OUTCOME MEASURE Deaths from abdominal aortic aneurysm in the five years after the start of screening . RESULTS The corrected response to invitation to screening was 70 % . The crude prevalence was 7.2 % for aortic diameter > or = 30 mm and 0.5 % for diameter > or = 55 mm . Twice as many men in the intervention group than in the control group underwent elective surgery for abdominal aortic aneurysm ( 107 v 54 , P = 0.002 , chi2 test ) . Between scheduled screening and the end of follow up 18 men in the intervention group and 25 in the control group died from abdominal aortic aneurysm , yielding a mortality ratio of 0.61 ( 95 % confidence interval 0.33 to 1.11 ) . Any benefit was almost entirely in men aged between 65 and 75 years , where the ratio was reduced to 0.19 ( 0.04 to 0.89 ) . CONCLUSIONS At a whole population level screening for abdominal aortic aneurysms was not effective in men aged 65 - 83 years and did not reduce overall death rates . The success of screening depends on choice of target age group and the exclusion of ineligible men . It is also important to assess the current rate of elective surgery for abdominal aortic aneurysm as in some communities this may already approach a level that reduces the potential benefit of population based screening BACKGROUND One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events ( ESSENCE ) trial show that use of low-molecular-weight heparin ( enoxaparin ) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infa rct ion is associated with a 10 % reduction in the cumulative 1-year risk of death , myocardial infa rct ion , or recurrent angina . Given the higher acquisition cost of enoxaparin relative to unfractionated heparin , we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada . METHODS AND RESULTS We analyzed cumulative 1-year re source use data on the 1259 ESSENCE patients enrolled in Canadian centers ( 40 % of the total ESSENCE sample ) . Patient-specific data on use of drugs , diagnostic cardiac catheterization , percutaneous transluminal coronary angioplasty , coronary artery bypass grafting , and hospital days were available from the initial hospital stay and cumulative to 1 year . Hospital re sources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project . During the initial hospital stay , use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures , with the largest effect being reduced use of percutaneous transluminal coronary angioplasty ( 15.0 % vs 10.6 % ; P = .03 ) . At 1 year , the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin , producing a cost-saving per patient of $ 1485 ( 95 % confidence interval $ -93 to $ 3167 ; P = .06 ) . Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $ 1075 per patient over a period of 1 year . CONCLUSIONS The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ( $ 101 vs $ 39 ) , but in patients with acute coronary syndrome , the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost . Evidence from this Canadian sub study of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication OBJECTIVES To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm ( AAA ) in men . DESIGN A trial of ultrasound screening for AAA in a population -based r and om sample of men aged 65 - 83 years , and a cross-sectional case-control comparison of men in the same sample . PARTICIPANTS 12,203 men who had an ultrasound examination of their abdominal aorta , and completed a question naire covering demographic , behavioural and medical factors . MAIN OUTCOME MEASURES Prevalence of AAA , and independent associations of AAA with demographic , medical and lifestyle factors . RESULTS Invitations to screening produced a corrected response of 70.5 % . The prevalence of AAAs ( > 30 mm ) rose from 4.8 % in men aged 65 - 69 years to 10.8 % in those aged 80 - 83 years . The overall prevalence of large ( > 50 mm ) aneurysms was 0.69 % . In a multivariate logistic model Mediterranean-born men had a 40 % lower risk of AAA ( > 30 mm ) compared with men born in Australia ( odds ratio [ OR ] , 0.6 ; 95 % CI , 0.4 - 0.8 ) , while ex-smokers had a significantly increased risk of AAA ( OR , 2.3 ; 95 % CI , 1.9 - 2.8 ) , and current smokers had even higher risks . AAA was significantly associated with established coronary and peripheral arterial disease and a waist : hip ratio greater than 0.9 ; men who regularly undertook vigorous exercise had a lower risk ( OR , 0.8 ; 95 % CI , 0.7 - 1.0 ) . CONCLUSION Ultrasound screening for AAA is acceptable to men in the likely target population . AAA shares some but not all of the risk factors for occlusive vascular disease , but the scope for primary prevention of AAA in later life is limited This study examines the rate of expansion of abdominal aortic aneurysms and the risk of rupture in relation to their size . To assess these variables , we conducted a prospect i ve study of 300 consecutive patients who presented over a 6-year interval with abdominal aortic aneurysms ( AAA ) that were initially managed nonoperatively . The mean age of the patients was 70.4 years , and 211 ( 70 % ) were men . The mean initial aneurysm diameter was 4.1 cm . Among the 208 patients who underwent more than one ultrasound or computed tomographic ( CT ) scan , the diameter of the aneurysm increased by a median of 0.3 cm per year . The 6-year cumulative incidence of rupture was 1 % and 2 % among patients with aneurysms less than 4.0 cm and 4.0 to 4.9 cm in diameter , respectively ( p greater than 0.05 ) . In comparison , the 6-year cumulative incidence of rupture was 20 % among patients with aneurysms greater than 5.0 cm in diameter ( p less than 0.004 ) . We conclude that ( 1 ) abdominal aortic aneurysms exp and at a median rate of 0.3 cm per year ; and ( 2 ) the risk of rupture of abdominal aortic aneurysms less than 5.0 cm is substantially lower than the risk of rupture of aneurysms 5.0 cm or more in diameter Ruptured abdominal aortic aneurysms ( RAAA ) have a 78 - 94 % mortality rate . If cost-effectiveness of screening programs for abdominal aortic aneurysms ( AAA ) are to be assessed , direct costs for RAAA repairs and elective AAA ( EAAA ) repairs are required . This study reports mortality , morbidity , and direct costs for RAAA and EAAA repairs in Nova Scotia in 1997 - 1998 and also compares Nova Scotia and U.S. costs . We performed a retrospective study of 41 consecutive RAAA and 48 r and omly selected EAAA patients . Average total costs for RAAA repair were significantly greater than those for EAAA repair ( direct costs : $ 15,854 vs. $ 9673 ; direct plus overhead costs : $ 18,899 vs. $ 12,324 [ pricing in 1998 Canadian dollars ] ) . Intensive care unit length of stay and blood product usage were the most substantial direct cost differentials ( $ 3593 and $ 2106 ) . Direct cost for preoperative testing and surveillance was greater in the EAAA group ( $ 839 vs. $ 33 ) . Estimates of U.S. in-hospital RAAA and EAAA repair costs are more than 1.5 times Nova Scotia costs . Direct in-hospital RAAA repair costs are $ 6181 more than EAAA repair costs . These in-hospital cost data are key cost elements required to assess the cost-effectiveness of various screening strategies for earlier detection and monitoring of AAA within high-risk population s in Canada . Further studies are required to estimate cost per quality -adjusted-life-year gained for various AAA screening and monitoring strategies in Canada PURPOSE Based on the prospect i ve analysis of data on 680 patients undergoing surgery for nonruptured abdominal aortic aneurysm ( AAA ) and recorded in the Canadian Society for Vascular Surgery Aneurysm Registry , this study determines the late survival rate by comparison to an age- and sex-matched population , the causes of late death , the effect of heart-related death on late survival , and the prognostic variables that are associated with late survival . METHODS To identify the variables that were associated with survival , statistical methods included Kaplan-Meier analysis and Cox regression analysis . The Canadian Society for Vascular Surgery Aneurysm Registry provided ongoing current follow-up of patients . RESULTS The survival rate was 94.6 % at 1 month , 90.7 % at 1 year , 87.1 % at 2 years , 81.0 % at 3 years , 74.0 % at 4 years , 67.7 % at 5 years , and 60.2 % at 6 years . The late survival rate of patients with AAA is significantly less than the age- and sex-matched normal population ( 60.2 % versus 79.2 % ) . In the AAA group , heart-related causes of late death ( 44.4 % versus 34.1 % ) and cerebrovascular causes ( 8.3 % versus 5.8 % ) were more frequent . The calculated 5-year heart-related mortality rate is 14.3 % . This is higher than the heart-related mortality rate for the age- and sex-matched population , which is 6.4 % . Hence , the risk of heart-related death for patients who have undergone AAA repair is increased by 1.6 % per year . Vascular complications from aortic aneurysm repair or recurrent aneurysmal disease were an uncommon cause of late death : ruptured thoracic aneurysm , 1.5 % ; ruptured aortic false aneurysm , 1.5 % ; and aortoenteric fistula , 0 % . This incidence appears to be less than reported in earlier series . By Cox regression analysis , the variables that were significant predictors of a lower late survival rate were increased age , preoperative electrocardiogram indicating a previous myocardial infa rct ion , and elevated serum creatinine levels . CONCLUSIONS Because cardiac complications accounted for 68.8 % ( 22/32 ) of the 4.7 % in-hospital mortality rate ( i.e. , a heart-related mortality rate of 3.2 % ) , it seems reasonable to develop a strategy to reduce the cardiac operative risk by identifying and treating patients at high risk before operation . However , it is doubtful that a preoperative program that screens and treats all patients can be cost-effective in preventing late heart-related deaths BACKGROUND Endovascular aneurysm repair ( EVAR ) is a new technology to treat patients with abdominal aortic aneurysm ( AAA ) when the anatomy is suitable . Uncertainty exists about how endovascular repair compares with conventional open surgery . EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair . METHODS Between 1999 and 2003 , 1082 elective ( non-emergency ) patients were r and omised to receive either EVAR ( n=543 ) or open AAA repair ( n=539 ) . Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more , who were fit enough for open surgical repair ( anaesthetically and medically well enough for the procedure ) , were recruited for the study at 41 British hospitals proficient in the EVAR technique . The primary outcome measure is all-cause mortality and these results will be released in 2005 . The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per- protocol patients . FINDINGS Patients ( 983 men , 99 women ) had a mean age of 74 years ( SD 6 ) and mean AAA diameter of 6.5 cm ( SD 1 ) . 1047 ( 97 % ) patients underwent AAA repair and 1008 ( 93 % ) received their allocated treatment . 30-day mortality in the EVAR group was 1.7 % ( 9/531 ) versus 4.7 % ( 24/516 ) in the open repair group ( odds ratio 0.35 [ 95 % CI 0.16 - 0.77 ] , p=0.009 ) . By per- protocol analysis , 30-day mortality for EVAR was 1.6 % ( 8/512 ) versus 4.6 % ( 23/496 ) for open repair ( 0.33 [ 0.15 - 0.74 ] , p=0.007 ) . Secondary interventions were more common in patients allocated EVAR ( 9.8 % vs 5.8 % , p=0.02 ) . INTERPRETATION In patients with large AAAs , treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair . Any change in clinical practice should await durability and longer term results STUDY OBJECTIVE The present study was performed to determine the influence of a perioperative myocardial infa rct ion on long-term mortality in patients who have undergone elective vascular surgery . STUDY DESIGN This was a 4-year follow-up of patients who had undergone elective vascular procedures at a Veterans Affairs Medical Center . Between January 1989 and December 1990 , 115 consecutive patients underwent surgery for either an exp and ing abdominal aortic aneurysm ( AAA ) ( 38 % ) or for pain in the lower extremities ( 62 % ) . RESULTS Vital status at 4 years postsurgery was determined for all patients . Thirty-day postoperative mortality was 3 % , while estimates at 1 , 2 , 3 , and 4 years were 19 % , 26 % , 35 % , and 39 % , respectively . Of the 45 patients who died within 4 years following surgery , the major causes of death were cardiac ( 40 % ) , cancer ( 18 % ) , cerebrovascular ( 13 % ) , and peripheral vascular disease ( 11 % ) . Univariate predictors of 1-year mortality on preoperative evaluation were an abnormal ECG , moderate or greater sized exercise thallium defect and left ventricular ejection fraction < or = 40 % , and a perioperative myocardial infa rct ion . Univariate predictors of 4-year mortality were non-AAA surgery and diabetes mellitus . Perioperative myocardial infa rct ion was a marginally significant independent predictor of 1-year mortality ( p=0.06 ) , while the need for non-AAA surgery was a strong independent predictor at 4 years . CONCLUSIONS Cardiac mortality is the major cause of late death among patients undergoing elective vascular surgery . Although preoperative indicators of symptomatic coronary artery disease and nonfatal perioperative myocardial infa rct ion identified those individuals at increased mortality in the first postoperative year , the extent of vascular disease at presentation may be a more important determinant of long-term survival . A r and omized trial in such patients is needed to assess the best strategy for treating patients with coexistent coronary artery and vascular diseases An ultrasonography screening programme for detecting abdominal aortic aneurysm ( AAA ) in the community is described in which 7200 men and women aged between 65 and 80 years were contacted by letter . Of these , 4237 were screened ; the aorta was visualized in 4122 and 179 AAAs of 3 cm or more in diameter were detected ( 4.3 per cent ) . Criteria for surgery are suggested and the results of their application prospect ively over 6 years are discussed . Using these criteria , under 10 per cent of patients with ultrasonographically‐detected AAA should require surgery for this condition provided ultrasonography follow‐up is used OBJECTIVES To identify whether abdominal aortic aneurysm screening causes anxiety in those screened and whether the diagnosis of an aneurysm produces sustained anxiety in subjects in comparison with those in whom no abnormality is detected . DESIGN Prospect i ve case controlled study . MATERIAL S AND METHODS The 28-item General Health Question naire ( GHQ ) was used to assess psychological morbidity in 161 men attending for routine aneurysm screening in the Gloucestershire Aneurysm Screening Programme . One hundred men had a normal aorta and 61 were identified as having aneurysms . The GHQ was administered just before screening and 1 month later . An anxiety linear analogue scale was also used . RESULTS There was no difference in anxiety levels between those men with normal aortas and those with aneurysms either before or after screening . There was a statistically significant reduction in both these groups 1 month after screening . CONCLUSION This study shows that although the invitation to aneurysm screening may cause some mild anxiety , this is not prolonged even when an asymptomatic aneurysm is diagnosed Background : Screening for abdominal aortic aneurysm , and intervention with elective repair , can reduce the incidence of aneurysmal rupture by a half . If a screening programme is implemented , it is essential to determine appropriate follow up intervals for rescreening . This paper estimates probabilities of progression growth of aortic diameter to provide evidence for this . Methods : Data were taken from 2342 men aged 65–80 screened in the Chichester r and omised control trial , who have been followed up for an average of 11 years . Aortic diameter was modelled as a Markov process with four categories : < 30 mm ( normal ) , 30–44 mm , 45–54 mm , and ≥55 mm . Estimates of the probabilities of progressing to each higher category were obtained . Results : The probabilities of progression increased with greater initial aortic diameter . The estimated rates/year were 0.018 ( 95 % confidence interval 0.014 to 0.023 ) , 0.16 ( 0.12 to 0.20 ) , and 0.49 ( 0.35 to 0.70 ) respectively for moving up one category . The probabilities of moving from < 30 mm to ≥55 mm were estimated as 1 % in 5 years and 12 % in 15 years , while the corresponding figures for moving from 45–54 mm to ≥55 mm were 91 % and 99 % . There were differences in rates of progression according to age , with men over 70 years having rates about three times those of men under 70 . Conclusions : It seems unnecessary to follow up men with normal aortic diameter as they experience a low probability of reaching criteria for surgery even within 15 years . However , follow up intervals should be progressively shorter for those with greater aortic diameter , especially in those aged over 70 . Active follow up , for example every 3 months , is appropriate for men with an aortic diameter of 45–54 mm OBJECTIVES to determine safe and optimal intervals of rescreening and surveillance for AAA . METHODS hospital-based mass screening of 6339 65 - 73-year-old men from 1994 - 98 . 76.4 % attended . One hundred and ninety-one ( 4 % ) had AAA53 cm . Twenty-four ( 0.5 % ) were initially > 5 cm and referred for surgery , while the rest were offered annual control scans to check for expansion . Later , all 348 ( 7.5 % ) men who 3 to 5 years ago had an ectatic aorta ( infrarenal aortic diameter of 25 - 29 mm or distal/renal aortic diameter ratio > 1.2 ) were offered rescreening . Of these , 62 ( 18 % ) died before rescanning , while 248 of the survivors attended rescreening ( 87 % ) . Furthermore , a r and om sample of 380 of those with non-ectatic aortas were offered rescreening . Of these , 49 ( 13 % ) died before rescreening ( p=0.06 ) , while 275 ( 83 % ) of the survivors attended re-screening . RESULTS none of the controls had developed AAA . Of those who initially had an 25 - 29 mm aorta , 29 % had developed AAA ( size range 30 - 48 mm ) with expansion rates varying from 1.0 to 4.7 mm/year . Only 3.5 % with a ratio > 1.2 developed AAA ( size range : 30 - 34 mm ) with expansion rates from 1.3 to 2.4 mm/year . During the fourth year of surveillance some AAA initially sized below 3.5 cm exp and ed to above 5 cm , while some sized 3.5 - 3.9 cm did so during the second year , > 4 cm did so during the first year of surveillance . CONCLUSION rescreening for AAA can be restricted to initially ectatic aortas sized 25 - 29 mm at 5-year intervals . Surveillance of small AAA can be restricted to 1 - 4 year intervals From family medical practice s 15775 men and women aged 65‐80 years were identified and r and omized into two groups : one group was invited for ultrasonographic screening for abdominal aortic aneurysm ( AAA ) , and the other acted as age‐ and sex‐matched controls . Of the 7887 invited for screening 5394 ( 68·4 per cent ) accepted . AAA was detected in 218 ( 4·0 per cent overall and 7·6 per cent of men ) . Aortic surgery was offered to the screened group if certain criteria were met and no patient died from rupture who was fit for operation and accepted elective treatment . The incidence of rupture was reduced by 55 per cent in men in the group invited for screening , compared with controls . The incidence of rupture in women was low in both groups A previous article ( Part I ) described the patient population and operative management of 666 patients who had surgery for nonruptured abdominal aortic aneurysms . This article details the perioperative complications and , by chi-square and logistic regression analysis , identifies the variables that are associated with each complication . In summarizing the results ( below ) the incidence of each complication is listed , along with the predictive risk factors in parentheses that have significance levels less than 0.05 . Vascular morbidity data are as follows : intraoperative bleeding , 4.8 % ; postoperative bleeding requiring transfusion , 2.3 % or repeat operation , 1.4 % ( large volume of blood transfusion and /or use of an autotransfusion device ) ; intraoperative limb ischemia , 3.5 % ; graft thrombosis , 0.9 % ( femoropopliteal disease and /or distal anastomosis at the femoral level ) ; distal thromboembolism , 3.3 % ( male sex , femoral popliteal disease , and /or intraoperative graft thrombosis ) ; amputation , 1.2 % ; graft infection , 1 case . General morbidity data are as follows : cerebrovascular event , 0.6 % ; paraplegia , 1 case ; cardiac event , 15.1 % ( age , previous episode of congestive heart failure , and /or electrocardiogram [ ECG ] evidence of a previous myocardial infa rct ion ) ; myocardial infa rct ion , 5.2 % ( advancing age , angina , and /or prolonged aortic cross-clamp time ) ; congestive heart failure , 8.9 % ( previous history of congestive heart failure , ECG evidence of ischemia , and /or chronic obstructive lung disease ) ; arrhythmia requiring treatment , 10.5 % ( preoperative ventricular premature beats and /or respiratory failure requiring ventilation for more than 48 hours ) ; new arrhythmia , 8.4 % ( angina and /or chronic obstructive lung disease ) ; respiratory failure , 8.4 % ( chronic obstructive lung disease , large volume of blood transfused , and /or occurrence of postoperative bleeding , cerebrovascular accident , congestive heart failure , or myocardial infa rct ion ) ; renal damage with rise in creatinine or blood urea nitrogen , 5.4 % and /or renal failure requiring dialysis , 0.6 % ( elevated preoperative creatinine , suprarenal aortic cross-clamping , and /or renal vein ligation ) ; diarrhea without evidence of ischemia colitis , 7.1 % and ischemic colitis , 0.6 % ( pelvic flow interrupted ) ; prolonged ileus , 11.0 % ( aortoiliac occlusive disease , deterioration of renal function , prolonged ventilation , and /or preoperative history of angina ) ; superficial wound infection , 1.5 % and deep infection , 0.5 % ( femoral anastomosis and /or female sex ) ; coagulopathy , 1.1 % ( large volume of blood transfused ) . ( ABSTRACT TRUNCATED AT 400 WORDS AIM To investigate the efficacy of a single ultrasonic scan at age 65 to identify patients at risk from ruptured abdominal aortic aneurysm ( AAA ) . METHOD A total of 6058 men aged 64 - 81 were recruited to a r and omised trial , and 3000 were invited to attend a single screening test . An additional population of 1011 men was offered screening as they reached age 65 . If a normal aorta was identified in this sub-group , further scans were offered at two-yearly intervals . Follow up and treatment of those identified as having an aortic dilatation of 3 cm or greater was undertaken . All subject groups were monitored for deaths occurring over the study period , and date and cause of death were recorded . RESULTS A total of 2212 men attended screening in the r and omised trial ; the overall compliance was 74 % , and prevalence of AAA was 7.7 % . Compliance decreased , and prevalence increased , with age . Mortality from ruptured AAA was reduced by 68 % at 5 years ( screened group compared to the age-matched control population ) , and by 42 % in the study arm ( screened and refusers ) compared with controls . The benefit persisted at ten years ( 53 % and 21 % respectively ) . Of the uncontrolled sample of 1011 men offered a scan at age 65 , 681 attended and 649 of these were found to have a normal aortic diameter ; re-screening demonstrated new aneurysm development in 4 % over ten years . The aortic diameters of the new AAAs were under 4 cm and would therefore have a low risk of rupture.1 Mortality from rupture in all those with an initially normal aortic diameter was low , at 1 case per 1000 scans over ten years . CONCLUSION Screening once for AAA at age 65 can identify the majority of AAA that are of clinical significance and can identify a large population at low risk from rupture who do not require surveillance . This policy has been effective when combined with selective treatment in reducing the risk of rupture for ten years in those who attend the screening programme |
11,211 | 16,235,401 | Insufficient evidence was found to support the efficacy of one exercise intervention over another .
This review has demonstrated an absence of evidence to support one form of exercise intervention against another and the use of supplementary exercises in the management of isolated ACL injuries . | BACKGROUND The anterior cruciate ligament ( ACL ) is the most frequently injured ligament of the knee .
Injury causes pain , effusion and inflammation leading to the inability to fully activate the thigh muscles .
Regaining muscular control is essential if the individual wishes to return to pre-injury level of function and patients will invariably be referred for rehabilitation .
OBJECTIVES To present the best evidence for effectiveness of exercise used in the rehabilitation of isolated ACL injuries in adults , on return to work and pre-injury levels of activity . | 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 Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months ( range , 27 to 44 ) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects . Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance , double-legged stance , or both , with the eyes open and closed . Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open . Total sagittal plane laxity was significantly greater in the anterior cruciate ligament-reconstructed knee ( 11.2 mm ; range , 6 to 15 ) than in the uninjured knee ( 8.9 mm ; range , 6 to 12 ) or in the control group ( 6.0 mm ; range , 5 to 8) . In spite of this , the patients , in comparison with the controls , exhibited normal postural control except in two variables — the reaction time and the latency between the start of force movement to maximal sway in the sagittal plane perturbations . This supports the hypothesis that rehabilitation , with proprioceptive and agility training , is an important component in restoring the functional stability in the anterior cruciate ligament-reconstructed knee The correlation between the prospect i ve course of proprioceptive improvement and knee stability after anterior cruciate ligament reconstruction was investigated in 38 patients . Proprioception , on the basis of the patient ’s capacity to reposition the limb accurately , was evaluated at 3-month intervals for 24 months after hamstring graft anterior cruciate ligament surgery . Knee stability was evaluated concurrently with a KT-2000 knee arthrometer . Thirty patients experienced improvement in postoperative position sense in at least one of the examinations , although eight patients had no improvement at any time . Of the 30 patients who had improvement , 28 maintained improved position sense from 18 months to the final followup . Thirty patients maintained significantly better knee stability for a postoperative period of at least 24 months . These results indicated that a minimum of 18 months after anterior cruciate ligament reconstruction may be needed for complete restoration of the proprioceptive function in knees , although the mean position sense in all patients gradually improved from 9 months . Improvement in postoperative knee stability may have facilitated recovery of proprioception The efficacy of two non-operative rehabilitation programs was studied in a consecutive r and omized controlled clinical trial of 100 patients after 12 months subsequent to an acute anterior cruciate ligament ( ACL ) injury . Follow up of r and omization to two training models was evaluated after 3 and 12 months : A self-monitored training program ( SM ) of traditional mobility and muscle strength training of the injured leg was compared to a supervised ( SV ) training model exercising postural function in closed kinetic-chains . Nearly 50 % of the patients in the SM group required supervision after 6 weeks . An intention-to-treat analysis was performed and showed significantly better values in most of the results of the supervised group at 3 and 12 months . An alternative analysis of subgroups showed a significant difference between transferred male patients and original SV male patients at 3 months but not at 12 months , indicating the importance of initial guiding after an ACL injury . No such difference was observed in the female patients |
11,212 | 19,286,397 | According to the best- evidence synthesis , however , there is no evidence from the available RCTs for differences in outcome in pain and shoulder function between conservatively and surgically treated patients with SIS . | BACKGROUND Patients with subacromial impingement syndrome are often operated on when conservative treatments fail .
But does surgery really lead to better results than nonoperative measures ?
This systematic review compared effects of conservative and surgical treatment for subacromial impingement syndrome in terms of improvement of shoulder function and reduction of pain . | This paper provides an up-to- date overview of the occurrence , diagnosis , risk factors , prognostic indicators and outcome of shoulder disorder ( SD ) , and of the validity and reproducibility of diagnostic classifications and diagnostic imaging techniques for SD . Furthermore , the available evidence on the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) , corticosteroid injections and physiotherapy for SD is summarized on the basis of r and omized controlled trials with an acceptable quality of their methods . The annual incidence of SD is estimated at about 7 % , its 1-year period prevalence at about 51 % and its lifetime prevalence at about 10 % . While approximately 50 % of all patients with SD seek medical care , about 95 % are treated in primary health care . Of all new episodes of SD presenting to primary care , approximately 50 % seem to resolve within 6 months , while about 40 % seem to persist for up to 12 months . Several prognostic indicators for a favourable or a poor outcome of SD have been identified , but a comprehensive prognostic model is not available . While evidence for the prognostic validity of popular diagnostic classifications of SD is lacking , their reproducibility has been shown to be poor . The accuracy and clinical usefulness of diagnostic imaging techniques appear to be sufficiently verified for SD in secondary care , while their clinical usefulness in primary care and prognostic validity are not . NSAIDs and steroid injections for SD have been shown to be effective within 6 weeks , but their effect on long-term outcome remains unclear . There is very limited evidence for the effectiveness in SD of physiotherapy , including exercise therapy , ultrasound , electrotherapy , laser , mobilization and manipulation OBJECTIVES To compare the effect of grade d physiotherapeutic training of the rotator cuff versus arthroscopic subacromial decompression in patients with subacromial impingement . METHODS R and omised controlled trial with 12 months ' follow up in a hospital setting . Ninety consecutive patients aged 18 to 55 years were enrolled . Symptom duration was between six months and three years . All fulfilled a set of diagnostic criteria for rotator cuff disease , including a positive impingement sign . Patients were r and omised either to arthroscopic subacromial decompression , or to physiotherapy with exercises aim ing at strengthening the stabilisers and decompressors of the shoulder . Outcome was shoulder function as measured by the Constant score and a pain and dysfunction score . " Intention to treat " analysis was used , with comparison of means and control of confounding variables by general equation estimation analysis . RESULTS Of 90 patients enrolled , 84 completed follow up ( 41 in the surgery group , 43 in the training group ) . The mean Constant score at baseline was 34.8 in the training group and 33.7 in the surgery group . After 12 months the mean scores improved to 57.0 and 52.7 , respectively , the difference being non-significant . No group differences in mean pain and dysfunction score improvement were found . CONCLUSIONS Surgical treatment of rotator cuff syndrome with subacromial impingement was not superior to physiotherapy with training . Further studies are needed to qualify treatment choice decisions , and it is recommended that sample s are stratified according to disability level In a r and omized prospect i ve study , we selected 15 patients for arthroscopic subacromial decompression ( ASD ) and 19 patients for open subacromial decompression ( OSD ) . All had impingement syndrome ( Neer grade II ) , and had been unsuccessfully treated without surgery for more than 6 months . The UCLA Shoulder Rating Scale , Visual Analogue Scales for pain and satisfaction , isokinetic dynamometer recordings and physical testing were assessed preoperatively and at 1 ( except isokinetic testing ) , 3 , 6 , and 12 months , and , finally , 8 years after surgery . We found essentially no differences in the clinical tests between the groups during this period . The use of ASD or OSD seems to be a matter of cosmesis and personal preference Objectives : To compare the prognosis of subacromial impingement ( SAI ) stage II treated conservatively or with subacromial decompression . Methods : A follow‐up study after 4–8 years in a r and omized controlled trial ( RCT ) with 90 adult cases with SAI treated in a Danish hospital from 1996 to 2000 with grade d physiotherapy and exercises or arthroscopic subacromial decompression . Outcomes were proportion of time per year with income transfers ( indexed 0–1 ) , including total transfers ( marginalization ) , sick leave and disability pension obtained from the registry at the Ministry of Work . Self‐reported function , working capability , employment status and global improvement were obtained by question naire in September 2004 . The main outcomes are given as differences in development from baseline . Results : Seventy‐nine ( 88 % ) responded to the question naire and registry data were obtained from 81 . After 1 year the marginalization index increased by 0.45 [ 95 % confidence interval ( CI ) 0.35–0.56 ] for surgery and 0.25 ( 0.16–0.34 ) for physiotherapy . Cases undergoing surgery also tended to have more sick payments during the first year , but the difference was not significant . Four years after inclusion , changes in indices did not differ between treatment groups . Self‐reported outcomes after 4–8 years did not differ between treatment groups . Conclusion : The results of surgical decompression were equal to those of conservative treatment , and the surgery group had more income transferrals during the first year of follow‐up Anterior acromioplasty as described by Neer has been an effective procedure for shoulder impingement syndrome . Artroscopic acromioplasty is regarded as a technically dem and ing procedure . Since 1988 we have developed a closed percutaneous acromioplasty using motorized instruments . The purpose of this r and omised clinical trial was to compare the results of open and closed percutaneous acromioplasty . We found a significant improvement in shoulder score , but no differences between the group treated with the open procedure and the group treated with the closed procedure OBJECTIVE To evaluate the effect of surgical treatment of the impingement syndrome of the shoulder on the fitness for work . DESIGN Retrospective . SETTING Academic Hospital Groningen , department of Orthopaedics , the Netherl and s. PATIENTS AND METHODS A group of 31 patients who had undergone an anterior shoulder decompression between 1 January 1984 and 31 December 1993 because of shoulder symptoms due to impingement lasting more than one year , were subjected in January 1996 to a study of the effect of the treatment on the pain , fitness for work and participation in the labour process . The results were measured using an objectivated score list for pain and function and with a comparison of the labour situations before and after the operation as described by the patients . RESULTS End results as measured with the score list were fair to good in 97 patients ( 74 % ) . The numbers of those completely fit for work before operation and at follow-up were identical , viz . 45 out of 131 ( 34 % ) . Thirty-four patients ( 26 % ) had other jobs or adjusted activities and 37 ( 28 % ) were completely unfit for work ( together 71 patients : 54 % ) ; 15 patients ( 11 % ) had stopped working for reasons of age . The probability to be definitely rejected for work after the operation was increased significantly by a job causing shoulder overstrain and by having been on sick leave with pay prior to the operation . CONCLUSION Although the objective results were reasonably good , the percentage of those completely fit for work was not changed appreciably by the surgical treatment OBJECTIVE --To compare the effectiveness of arthroscopic surgery , a supervised exercise regimen , and placebo soft laser treatment in patients with rotator cuff disease ( stage II impingement syndrome ) . DESIGN --R and omised clinical trial . SETTING --Hospital departments of orthopaedics and of physical medicine and rehabilitation . PATIENTS --125 patients aged 18 - 66 who had had rotator cuff disease for at least three months and whose condition was resistant to treatment . INTERVENTIONS --Arthroscopic subacromial decompression performed by two experienced surgeons ; exercise regimen over three to six months supervised by one experienced physiotherapist ; or 12 sessions of detuned soft laser treatment over six weeks . MAIN OUTCOME MEASURES --Change in the overall Neer shoulder score ( pain during previous week and blinded evaluation of function and range of movement by one clinician ) after six months . RESULTS --No differences were found between the three groups in duration of sick leave and daily intake of analgesics . After six months the difference in improvement in overall Neer score between surgery and supervised exercises was 4.0 ( 95 % confidence interval -2 to 11 ) and 2.0 ( -1.4 to 5.4 ) after adjustment for sex . The condition improved significantly compared with placebo in both groups given the active treatments . Treatment costs were higher for those given surgery ( 720 pounds v 390 pounds ) . CONCLUSIONS --Surgery or a supervised exercise regimen significantly , and equally , improved rotator cuff disease compared with placebo Forty-two patients with subacromial impingement syndrome entered a r and omized prospect i ve study comparing open anterior acromioplasty with a physiotherapy regime . The criterion for a successful outcome of treatment was a reduction of the initial pain score of more than 50 % using the visual analogue scale ( VAS ) technique . The evaluation was performed by an independent observer . At the 6-month follow-up , treatment in the surgical group had been successful in 12/21 ( 57 % ) patients versus 6/18 ( 33 % ) in the physiotherapy group . A one-year evaluation revealed 16/21 ( 76 % ) " successes " in the surgical group . A direct and unbiased comparison with the physiotherapy group was not possible at one year , since 13 patients chose surgery after initial physiotherapy . However , in " an intention to treat " analysis outcome at one year was significantly better in those r and omized to surgery . We found two st and ardized , composite , active movements -- the " Pour out of a Pot " manoeuvre requiring the emptying of a pot of water , and the " H and in Neck " manoeuvre -- to be of predictive value for the outcome of surgery . When combining three pain-related variables into a criterion for prediction of success , a sensitivity of 78 % ( p < 0.02 ) and a specificity of 90 % ( p < 0.03 ) were attained . We advance the hypothesis that pain in the impingement syndrome is mainly elicited by comparison of the subacromial bursa . In some patients a traction-responsive pain generator in the supraspinatus tendon may be present as well The results of open subacromial decompression ( OSD ) were compared with arthroscopic subacromial decompression ( ASD ) after 1 year in 32 subjects ( 4 bilateral ) , and the correlation between the two shoulder rating scales for impingement was documented . Patients were evaluated clinical ly on the modified University of California at Los Angeles ( UCLA ) shoulder rating scale , and Constant scale . Scapular position and rotation were evaluated as well as a rotation and abduction shoulder strength test using the Cybex II dynamometer . No parameters revealed significant differences between the groups , except for the UCLA score which indicated an advantage for the ASD group ( p = 0.046 ) . The OSD group scored 24.5 ( 5.45 ) on the UCLA scale and 73.8 ( 18.9 ) on the Constant scale , whereas the ASD group scored 28.3 ( 5.6 ) and 80.8 ( 16.4 ) . To study the correlation between both scales , the Pearson correlation product-moment coefficient was calculated and a high correlation ( r = 0.81 ) obtained . Less mobility was found in the operated arm for all parameters , with the exception of glenohumeral abduction in both groups and passive elevation in the OSD group . Only in the OSD group did the scapula in the operated extremity show more abduction of the inferior angle of the scapula . Weaker abduction strength in the operated side was found in the ASD group , whereas in the OSD group there was significantly less adduction and external rotation strength at 180 degrees/s en 240 degrees/s . We conclude that after one year the open group tends to catch up with the arthroscopic patients and that the main benefits after arthroscopic surgery as described in literature are more evident in the shorter period The effectiveness of arthroscopic surgery , supervised exercises , and placebo was compared in 125 patients with rotator cuff disease ( impingement syndrome stage II ) in a r and omized clinical trial . The median age was 48 years , and the median duration of complications was 1 to 2 years . The treatments were arthroscopic subacromial decompression performed by 2 experienced surgeons , an exercise regimen supervised for 3 to 6 months by 1 experienced physiotherapist , or 12 sessions of detuned soft laser ( placebo ) for 6 weeks . The criterion for success was a Neer shoulder score > 80 . Fifteen ( 50 % ) and 11 ( 22 % ) of the patients r and omized to placebo and exercises , respectively , had surgery during the 2 1/2-year follow-up period and were classified as having failure with the treatments . The success rate was higher ( P < .01 ) for patients r and omized to surgery ( 26 of 38 ) and exercises ( 27 of 44 ) compared with the placebo group ( 7 of 28 ) . The odds ratio for success after surgery compared with exercises was 1.5 ( 95 % confidence interval 0.6 to 3.7 ; P = .49 ) . Including all patients who underwent operation , the success rate in those not on sick leave ( 19 of 21 ) before surgery was higher compared with those on sick leave ( 18 of 36 ) ( adjusted odds ratio 5.6 [ 1.2 to 29.2 ] ) . Similar results were observed for patients not receiving versus those receiving regular pain medication before surgery ( adjusted odds ratio 4.2 [ 1.2 to 15.8 ] ) Arthroscopic subacromial decompression was performed on 114 patients with rotator cuff impingement who had not responded to nonoperative measures . None of the patients had a full-thickness cuff tear . Patients with associated instability , symptomatic acromioclavicular joint disease , or ruptures of the long head of biceps were not included . Results were determined by question ing patients about their satisfaction with the outcome of surgery and by functional assessment of the shoulder with the parameters of pain , ability to perform daily activities , and range of motion according to the Constant scoring system . When review ed at a mean interval of 19 months after surgery , 85 patients ( 75 % ) were satisfied with the outcome . Pain scores improved by an average of 8.6 points ; " activities of daily living " scores improved by an average of 5.8 points ; range-of-motion scores improved by an average of 3.6 points . The improvements in all 3 parameters scored were significant ( P < .05 ) . The following variables were statistically analyzed to assess their influence on final outcome : age , sex , occupation , duration of symptoms before surgery , dominance of the affected shoulder , outcome of the impingement test , state of the cuff , and experience of the surgeon performing the operation . The duration of symptoms before surgery was the most significant predictor of outcome . Symptoms of prolonged duration were associated with an unsatisfactory subjective results ( P < .01 ) and with smaller improvements in the parameters of the Constant score ( P < .001 ) . Recovery after arthroscopic subacromial decompression and eventual outcome were related to the extent of cuff damage . Patients with partial thickness tears or fraying of the cuff had a delayed return to work ( P < .001 ) and were found to have smaller increases in the pain and range-of-motion scores ( P < .05 ) . A satisfactory subjective result was most often associated with a positive impingement test ( P < .05 ) . Unsatisfactory outcomes were associated with a question able diagnosis and lack of clear evidence of impingement at arthroscopy , inadequate decompression of the subacromial space , or the presence of calcium deposits in the rotator cuff Between May 1988 and May 1990 , 44 patients with Stage II impingement were r and omized into open and arthroscopic treatment groups . Forty-one patients were available for final follow-up in May 1991 : 22 in the open group , 19 in the arthroscopic group . Comparisons of pain , function , motion , and strength were made preoperatively and at 2 , 6 , 12 , 26 , and 52 weeks postoperatively . Final analysis showed that the main benefits of arthroscopic acromioplasty were evident in the first 3 months postoperatively . Arthroscopic patients regained flexion and strength more rapidly than did open patients , had shorter hospitalizations , used less narcotics , and returned more quickly to both work and activities of daily living . By 3 months postoperatively , open patients tended to " catch up " with arthroscopic patients , and further recovery was equivalent . In both groups , full recovery took at least 1 year for the majority of patients and in both groups at 1 year > 90 % of patients achieved a satisfactory result . Because of its medical and economic advantages for both the patient and the health-care system , we conclude that arthroscopic acromioplasty should become the procedure of choice for patients with impingement syndrome refractory to conservative treatment The purpose of this study is to determine whether arthroscopic acromioplasty is equivalent or superior to open acromioplasty , in a prospect i ve , r and omized , controlled , blinded clinical trial . Seventy-one patients with a clinical diagnosis of impingement syndrome were r and omized to arthroscopic or open acromioplasty . Nine were excluded because of full-thickness rotator cuff tears diagnosed after r and omization . Sixty-two patients ( 49 men and 13 women ) with a minimum follow-up of 12 months ( mean , 25 months ) were included . The patient groups were virtually identical with regard to duration of symptoms , shoulder functional dem and s , age , sex , h and dominance , mechanism of onset , range of motion , strength , joint laxity , and the presence of a compensation cl aim . Patients were prospect ively r and omized to arthroscopic or open acromioplasty after stratification for age ( > 50 years),associated ligamentous laxity , and the presence of an ongoing compensation cl aim . The main outcome measure was visual analog scales for pain and function . Also recorded were UCLA shoulder scores and visual analog scales for postoperative improvement , patient satisfaction , and a variety of clinical measures . An independent blinded examiner assessed all patients . There was no significant difference between open and arthroscopic acromioplasty in visual analog scales for postoperative improvement ( P = .30 ) , patient satisfaction ( P = .94 ) , UCLA shoulder score ( P = .69 ) , or strength ( P = .62 ) ; however , open was superior to arthroscopic acromioplasty for pain and function ( P = .01 ) . Overall , 67 % of patients had a good or excellent result . This increased to 87 % when unsettled compensation cl aims were excluded . Repeat ( open ) acromioplasty was performed in 5 patients in the unsuccessful arthroscopic group without improvement . Open acromioplasty was equivalent to arthroscopic acromioplasty for UCLA scores and patient satisfaction . For pain and function , both gave significant improvement but the open technique may be superior . Unsettled compensation is a predictor of poor outcome |
11,213 | 21,069,663 | Magnesium sulphate more than halves the risk of eclampsia , and probably reduces maternal death .
There is no clear effect on outcome after discharge from hospital .
A quarter of women report side effects with magnesium sulphate | BACKGROUND Eclampsia , the occurrence of a seizure ( fit ) in association with pre-eclampsia , is rare but potentially life-threatening .
Magnesium sulphate is the drug of choice for treating eclampsia .
This review assesses its use for preventing eclampsia .
OBJECTIVES To assess the effects of magnesium sulphate , and other anticonvulsants , for prevention of eclampsia . | OBJECTIVES Our objective was to compare intramuscular ( i.m . ) magnesium sulfate with a low dose intravenous ( i.v . ) magnesium sulfate regimen in prevention of convulsion recurrence and maternal deaths in women with eclampsia . METHODS This prospect i ve trial was conducted in Nilratan Sircar Medical College , India from January 2001 to December 2005 . All women with a clinical diagnosis of eclampsia were included in the trial . Magnesium sulfate ( 4 gm ) was given as an i.v . loading dose , followed by either i.m . injections as recommended by Pritchard or low dose i.v . infusions ( 0.6 gm/h ) . Primary measures of outcome were recurrence of convulsions and maternal death . Secondary measures of outcome were potentially life threatening events , events related to labor and delivery as well as perinatal mortality and morbidity . RESULTS Of the 630 women participating in the trial , 480 women received i.m . magnesium sulphate according to the Pritchard regimen and 150 women were subjected to a low dose i.v . regimen of magnesium sulphate . There was no significant difference in recurrence of convulsion ( 3.3 % in the i.m . and 2 % in the i.v . groups P = 0.586 ) . Maternal deaths were not significantly lower in the i.v . group than the i.m . group ( 5 % in the i.m . and 3.3 % in the i.v . groups , P = 0.506 ) There were no significant differences in other measures of serious maternal morbidity , in perinatal morbidity or mortality . CONCLUSION Low dose i.v . magnesium sulfate regimen is equally effective in prevention of convulsion recurrence and maternal deaths in eclamptic women when compared with an i.m . magnesium sulfate regimen Abstract Objectives : To measure the incidence of eclampsia , establish how often it is preceded by signs of pre-eclampsia , document the morbidity associated with eclampsia , and determine the maternal case fatality rates . Design : A prospect i ve , descriptive study of every case of eclampsia in the United Kingdom in 1992 . Information was collected from review s of hospital case notes and question naires to general practitioners . Setting : All 279 hospitals in the United Kingdom with a consultant obstetric unit . Results : Obstetricians and midwives notified 582 possible cases , and 383 were confirmed as eclampsia . The national incidence of eclampsia was 4.9/10000 maternities ( 95 % confidence interval 4.5 to 5.4 ) . Most convulsions occurred despite antenatal care ( 70 % ) and within one week of the woman 's last visit to a doctor or midwife ( 85 % ) . Three quarters of first seizures occurred in hospital , of which 38 % developed before both proteinuria and hypertension had been documented . Forty four per cent of cases occurred postpartum , more than a third ( 38 % ) antepartum , and the remainder ( 18 % ) intrapartum . Nearly one in 50 women ( 1.8 % ) died , and 35 % of all women had at least one major complication . The rate of stillbirths and neonatal deaths was 22.2/1000 and 34.1/1000 , respectively . Preterm eclampsia occurred more commonly antepartum and was associated with more maternal complications and fetuses that were small for gestational age , as well as with higher rates of stillbirth and neonatal mortality . Antepartum eclampsia , which was more likely to occur preterm , was associated with a higher rate of maternal complications and a higher neonatal mortality . Both factors ( gestational prematurity and antepartum occurrence ) contributed independently to the severity of the outcome . Conclusion : Eclampsia occurs in nearly one in 2000 maternities in the United Kingdom and is associated with high maternal morbidity and fatality in cases . It may present unheralded by warning signs . Preterm and antenatal eclampsia seem to be particularly severe Objective To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclempsia in women with severe pre‐eclampsia OBJECTIVES To investigate whether in utero exposure to magnesium sulfate ( MgSO4 ) was associated with a lower prevalence of cerebral palsy ( CP ) in infants born weighing < 1500 g. DESIGN Singleton infants weighing < 1500 g at birth ( very low birthweight , VLBW ) and surviving to 3 years with moderate or severe congenital CP were identified among 155,636 children born 1983 through 1985 in four California counties . VLBW children with CP were compared with r and omly selected VLBW control survivors with respect to whether their mothers received MgSO4 to prevent convulsions in preeclampsia or as a tocolytic agent , and other information abstract ed from labor and delivery records . RESULTS During the admission for delivery , 7.1 % of the 42 VLBW infants with later CP and 36 % of the 75 VLBW controls were exposed to MgSO4 ( odds ratio ( OR ) .14 , 95 % confidence interval ( CI ) .05 , .51 ) . The overall association of MgSO4 with reduced risk of CP was also observed in the subgroup of infants born to women who were not preeclamptic ( OR .25 , CI .08 , .97 ) . Infants with CP were less often exposed antenatally to MgSO4 whether or not there was cotreatment with non-MgSO4 tocolytics ( other tocolytics administered , OR for MgSO4 exposure .23 , CI .06 , 1.2 ; other tocolytics not administered , OR for MgSO4 .08 , CI .02 , .68 ) , or antenatal corticosteroids ( steroids given , OR for MgSO4 exposure .24 , CI .06 , 1.3 ; steroids not given , OR for MgSO4 , .08 , CI .02 , .72 ) . Apparent benefit of magnesium was observed in the presence or absence of a variety of characteristics of pregnancies , births , and infants . CONCLUSION In this observational study , in utero exposure to MgSO4 was more frequent in controls than in children with CP , suggesting a protective effect of MgSO4 against CP in these VLBW infants Background The Magpie Trial , a r and omised trial comparing magnesium sulphate with placebo for women with pre-eclampsia . This paper describes methods used for follow up in the UK , and presents additional data collected . Methods In the UK 774 women and their 827 children were included ; excluded were women discharged without a surviving child and families who opted out . General practitioners were sent a question naire when the child was around 18 months old . When the child was two years , or older , question naires asking about the health of the women and children were posted to families . A sample of families was offered a home visit , during which the child was assessed using the Bayley Scales of Infant Development . Results Of the women , 12 were lost to follow up and three died . Of the children , 12 were lost to follow up , 5 were excluded and 19 died . General practitioners returned 688/759 ( 91 % ) question naires , as did 619/759 ( 82 % ) women . Responses were largely comparable . 32 women had serious morbidity potentially related to pre-eclampsia . 30 % of children were reported to have been admitted to hospital . There were no clear differences between the r and omised groups in the child 's behaviour , women 's fertility or use of health service re sources . Conclusion Data presented here provide further reassurance about the longer term safety of magnesium sulphate when used for women with pre-eclampsia . Postal question naires in the UK to assess the longer term health and wellbeing of women and children recruited to trials are feasible , and can achieve a high response rate . Responses from families and general practitioners were comparableTrial registration Trial registration number of the Magpie Trial [ IS RCT N86938761 Background The Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia . 10,141 women were recruited , 8804 before delivery . Overall , 9024 children were included in the analysis of outcome at discharge from hospital . Magnesium sulphate more than halved the risk of eclampsia , and probably reduced the risk of maternal death . There did not appear to be any substantive harmful effects on the baby , in the short term . It is now important to assess whether these benefits persist , and to provide adequate reassurance about longer term safety . The main objective of the Magpie Trial Follow Up Study is to assess whether in utero exposure to magnesium sulphate has a clinical ly important effect on the child 's chance of surviving without major neurosensory disability . Other objectives are to assess long term outcome for the mother , and to develop and assess appropriate strategies for following up large numbers of children in perinatal trials . Study design Follow up is only feasible in selected centres . We therefore anticipate contacting 2800–3350 families , for 2435–2915 of whom the woman was r and omised before delivery . A further 280–335 children would have been eligible for follow up if they had survived . The total sample size for the children is therefore 3080–3685 , 2680–3210 of whom will have been born to women r and omised before delivery . Families eligible for the follow up will be contacted , and surviving children screened using the Ages and Stages Question naires . Children who screen positive , and a sample of those who screen negative , will whenever possible have a paediatric and neurodevelopmental assessment . When women are contacted to ask how their child is , they will also be asked about their own health . The primary outcome is a composite measure of death or neurosensory disability for the child at 18 months . Discussion The Follow Up Study began in 2002 , and now involves collaborators in 19 countries . Data collection will close at the end of 2003 OBJECTIVE The primary outcome was to determine whether magnesium sulfate therapy prolongs the duration of labor in women with mild preeclampsia . Secondary outcomes were to assess the side effects associated with magnesium sulfate therapy : hours and maximum dose of oxytocin , incidence of progression to severe preeclampsia , incidence of cesarean delivery , change in maternal hematocrit , incidence of postpartum hemorrhage , incidence of maternal infection , and Apgar scores . STUDY DESIGN Women with a diagnosis of mild preeclampsia at term were r and omized to receive st and ard therapy during labor and for 12 hours post partum with either magnesium sulfate ( n = 67 ) or a matching placebo solution ( n = 68 ) . RESULTS There was no difference between magnesium sulfate and placebo with respect to the primary outcome variables : total length of labor ( median 17.8 hours vs 16.5 hours , p = 0.7 ) and length of the active phase of labor ( median 5.4 hours vs 6.0 hours , p = 0.5 ) . In addition , no difference was observed in the secondary outcome variables : hours of oxytocin use , change in hematocrit , frequency of maternal infection , progression to severe preeclampsia , incidence of cesarean delivery , and Apgar scores . Although not statistically significant , the incidence of postpartum hemorrhage was approximately fourfold greater in the magnesium sulfate group ( relative risk 4.1 , 95 % confidence interval 0.5 to 35.4 ) . There was a significant difference in the maximum dose of oxytocin used ( 13.9 + /- 8.6 mU/min with magnesium sulfate vs 11.0 + /- 7.6 mU/min with placebo , p = 0.036 ) . CONCLUSION The use of magnesium sulfate during labor in women with mild preeclampsia at term does not affect any component of labor but did necessitate a higher dose of oxytocin BACKGROUND Magnesium sulfate is used widely to prevent eclamptic seizures in pregnant women with hypertension , but few studies have compared the efficacy of magnesium sulfate with that of other drugs . Anticonvulsant prophylaxis with phenytoin for eclampsia has been recommended , but there are virtually no data to support its efficacy . Our objective was to compare magnesium sulfate with phenytoin in preventing seizures in hypertensive women during labor . METHODS We r and omly assigned women with hypertension who were admitted for delivery to receive either magnesium sulfate or phenytoin . The magnesium sulfate regimen consisted of a 10-g intramuscular loading dose followed by a maintenance dose of 5 g given intramuscularly every four hours . For women with severe preeclampsia , an additional 4-g loading dose was given intravenously . The phenytoin regimen included a 1000-mg loading dose infused over a period of 1 hour , followed by a 500-mg oral dose 10 hours later . With either regimen , anticonvulsant therapy was continued for 24 hours post partum . RESULTS Ten of 1089 women r and omly assigned to the phenytoin regimen had eclamptic convulsions , as compared with none of 1049 women r and omly assigned to magnesium sulfate ( P = 0.004 ) . There were no significant differences in any risk factors for eclampsia between the two study groups . Maternal and infant outcomes were also similar in the two study groups . CONCLUSIONS Magnesium sulfate is superior to phenytoin for the prevention of eclampsia in hypertensive pregnant women . These results vali date the long- practice d use of magnesium sulfate in the prevention of eclampsia OBJECTIVE To assess the effects of nimodipine on retinal blood flow in patients with pregnancy induced hypertension ( PIH ) . METHODS Fourteen patients were studied with color flow Doppler before and after 30 mg nimodipine administered orally , while other fourteen patients received intravenous magnesium sulfate as control group . Central retinal artery flow velocity waveforms were measured and pulse index ( PI ) were calculated . RESULTS Nimodipine reduced the central retinal artery PI significantly from 0.92 + /- 0.14 to 0.75 + /- 0.22 . It also reduced systolic blood pressure from 20.7 + /- 2.5 kPa to 19.8 + /- 1.5 kPa and diastolic blood pressure from 14.4 + /- 2.3 kPa to 13.6 + /- 1.9 kPa . CONCLUSIONS Nimodipine may dilate central retinal arteries . Changes in pulsatility index in retinal arteries maybe indicative of similar changes in other cerebral vessels . Nimodipine may be another choice of PIH therapy OBJECTIVE The purpose of this study was to assess the use of the onset of diuresis in the determination of the duration of postpartum magnesium sulfate therapy among patients with severe preeclampsia . STUDY DESIGN A prospect i ve r and omized trial of postpartum therapy with magnesium sulfate was conducted . The control group received 24 hours of therapy , and the study group received therapy until the onset of diuresis ( urine output > 100 mL/hr for 2 consecutive hours ) . The Student t test , chi 2 test , and Fisher 's exact test were used for analysis of data ; a probability value of < .05 was considered statistically significant . RESULTS There were 50 patients in the control group and 48 patients in the study group . There was no difference in maternal demographic data , severe disease criteria , blood pressure , 24-hour postpartum urine output , or need for antihypertensive therapy . The study group had a significantly shorter duration of therapy , and no patient had eclampsia or required the re-initiation of therapy . CONCLUSION The use of the onset of diuresis in the postpartum period as the determinant clinical parameter for the discontinuation of magnesium sulfate in patients with severe preeclampsia was associated with no untoward outcomes or need for the re-initiation of treatment OBJECTIVE Data are accumulating to suggest that cerebral perfusion pressure may be either abnormally high or low in preeclampsia and eclampsia . Little is known of the cerebral perfusion pressure effects of magnesium sulfate or nimodipine . Our objective in this study was to compare the change in cerebral perfusion pressure in patients with severe preeclampsia r and omly selected to receive nimodipine or magnesium sulfate . STUDY DESIGN Patients with severe preeclampsia were r and omly selected to receive magnesium sulfate ( 6 g bolus and 2 g/hr intravenous infusion ) or nimodipine ( 60 mg taken orally every 4 hours ) . Transcranial Doppler ultrasonography was used to measure flow velocities in the right and left middle cerebral arteries , and the results were averaged . Measurements were obtained before treatment ( baseline ) and 30 minutes after the magnesium sulfate bolus was completely infused or 30 minutes after the nimodipine was ingested . Studies were performed before any other intervention . The person performing the ultrasonography was unaware of the patient 's group assignment . Estimated cerebral perfusion pressure was calculated with the following formula : Estimated cerebral perfusion pressure = Velocity(mean ) x [ ( Blood pressure(mean ) - Blood pressure(diastolic ) ) /(Velocity(mean ) - Velocity(diastolic ) ) ] . The difference between estimated cerebral perfusion pressure at baseline and after treatment was compared between the 2 groups by means of the Mann-Whitney rank sum test . RESULTS Nine patients were r and omly selected to receive nimodipine and 12 to receive magnesium sulfate . Patient demographics and severity of condition were not significantly different between the 2 groups . The change in estimated cerebral perfusion pressure was significantly different between the groups . Estimated cerebral perfusion pressure increased after nimodipine use and decreased after magnesium sulfate use . CONCLUSION Shortly after administration to patients with severe preeclampsia , nimodipine result ed in increased cerebral perfusion pressure in comparison with magnesium sulfate OBJECTIVE Our purpose was to determine whether seizure prophylaxis with magnesium sulfate prolongs induction of labor in women with pregnancy-associated hypertension . STUDY DESIGN Women with a singleton pregnancy in vertex presentation between 32 and 42 weeks ' gestation who required induction of labor for either preeclampsia , preeclampsia superimposed on chronic hypertension , or transient hypertension were r and omized to receive either magnesium sulfate or phenytoin ( Dilantin ) for seizure prophylaxis . Women with rupture of the membranes , spontaneous contractions result ing in cervical change , or an initial cervical examination showing > 2 cm dilatation and 50 % effacement were excluded . RESULTS Fifty-four women were r and omized to receive either magnesium sulfate ( n = 28 ) or phenytoin ( n = 26 ) . The two groups were similar for selected maternal antepartum , intrapartum , and postpartum characteristics that have been associated with a prolongation or failure of labor induction . The two groups were also similar for the interval from the start of induction to ( 1 ) the first examination > or = 5 cm cervical dilatation and ( 2 ) delivery and in the frequency of women requiring cesarean delivery . CONCLUSION Compared with phenytoin , magnesium sulfate seizure prophylaxis in women with pregnancy-associated hypertension does not prolong the induction of labor nor does it result in an increase in cesarean deliveries The placenta and the umbilical cord obtained from 18 women with pregnancy‐induced hypertension were investigated by light microscopy . The umbilical artery was studied by electron microscopy . 10 placentae and umbilical cords from normal pregnancies served as controls . The study was performed as a double‐blind r and omized controlled study in which 11 women were allocated to magnesium and 7 to placebo treatment . The treatment comprised a 48‐hour intravenous magnesium/placebo infusion followed by daily oral magnesium/placebo intake until one day after delivery . Magnesium supplement increased birth weight and placental weight significantly . Light microscopic study of the placentae and the umbilical cord arteries showed no difference between the three groups concerning the occurrence of infa rct ions , cytotrophoblastic hyperplasia , vasculo‐syncytial membranes , basement membrane thickening , stromal fibrosis or intervillous fibrin . Ultrastructurally , the endothelial cells of the umbilical arteries from women with pregnancy‐induced hypertension showed a significant increase in the amount of dilated endoplasmatic reticulum and basal laminae thickness when all 18 cases were compared with the controls . There was no significant difference when the magnesium group , the placebo group and the control group were compared separately . The present study suggests that magnesium supplement has a benefical effect on fetal growth in pregnancy‐induced hypertension . With regard to the light and electron microscopic changes we were unable to demonstrate any significant difference between the magnesium , placebo and control groups Seizure prophylaxis is st and ard intrapartum therapy for patients with pregnancy-induced hypertension . Magnesium sulfate is used in the United States in spite of limited literature comparing its efficacy with other anticonvulsants . Fifty patients with pregnancy-induced hypertension were prospect ively r and omized to receive magnesium sulfate or phenytoin for seizure prophylaxis . Patients were observed for toxicity , side effects , and labor outcomes , and the neonates were evaluated for side effects of the therapy . Three patients were excluded with adverse reactions to medications ( one in magnesium sulfate group , two in phenytoin group ) . No differences were found in patient tolerance , adverse reactions , or neonatal outcomes between groups . Maternal free phenytoin levels were 13.0 % + /- 0.4 % of total phenytoin ( serum albumin , 2.5 to 3.5 gm/dl ) , significantly higher than in nonpregnant patients . Neither free phenytoin levels nor percentage of total phenytoin that was free correlated significantly with maternal albumin levels . The pharmacokinetics of phenytoin loading in the massively obese pregnant patient may differ and require further evaluation . Phenytoin is a well-tolerated alternative to magnesium sulfate for seizure prophylaxis in the patient with mild pregnancy-induced hypertension BACKGROUND Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions , and so improve outcome . Evidence supported magnesium sulphate as the drug to evaluate . METHODS Eligible women ( n=10141 ) had not given birth or were 24 h or less postpartum ; blood pressure of 140/90 mm Hg or more , and proteinuria of 1 + ( 30 mg/dL ) or more ; and there was clinical uncertainty about magnesium sulphate . Women were r and omised in 33 countries to either magnesium sulphate ( n=5071 ) or placebo ( n=5070 ) . Primary outcomes were eclampsia and , for women r and omised before delivery , death of the baby . Follow up was until discharge from hospital after delivery . Analyses were by intention to treat . FINDINGS Follow-up data were available for 10,110 ( 99.7 % ) women , 9992 ( 99 % ) of whom received the allocated treatment . 1201 of 4999 ( 24 % ) women given magnesium sulphate reported side-effects versus 228 of 4993 ( 5 % ) given placebo . Women allocated magnesium sulphate had a 58 % lower risk of eclampsia ( 95 % CI 40 - 71 ) than those allocated placebo ( 40 , 0.8 % , vs 96 , 1.9 % ; 11 fewer women with eclampsia per 1000 women ) . Maternal mortality was also lower among women allocated magnesium sulphate ( relative risk 0.55 , 0.26 - 1.14 ) . For women r and omised before delivery , there was no clear difference in the risk of the baby dying ( 576 , 12.7 % , vs 558 , 12.4 % ; relative risk 1.02 , 99 % CI 0.92 - 1.14 ) . The only notable difference in maternal or neonatal morbidity was for placental abruption ( relative risk 0.67 , 99 % CI 0.45 - 0.89 ) . INTERPRETATION Magnesium sulphate halves the risk of eclampsia , and probably reduces the risk of maternal death . There do not appear to be substantive harmful effects to mother or baby in the short term Background . Eclampsia remains a common cause of maternal death in Bangladesh . Early experience of magnesium sulphate use for eclampsia in Bangladesh was based on a lower dose regime , tailored for use in the smaller woman OBJECTIVE To determine whether only loading dose of magnesium sulfate is effective in controlling convulsion in eclampsia . STUDY METHODS This prospect i ve study was conducted in Dhaka Medical College and Hospital , Bangladesh between July and November 1999 . Eclamptic patients who were eligible for magnesium sulfate ( MgSO4 ) therapy were r and omly assigned by lottery to receive either only loading dose ( n = 202 ) or st and ard regime ( n = 199 ) of MgSO4 . Besides the anticonvulsant , patients of both the groups were managed by same protocol for eclampsia management prepared by Eclampsia Working Group , Bangladesh . Efficacy of both the regimes was assessed by measuring the rate of recurrent convulsion . Results were expressed as mean + /- SD and a proportion . Statistical analysis was done using unpaired t-test , Z-test and chi2 test as appropriate . A P-value of < 0.05 was considered significant . RESULTS At the time of r and omization there were no significant differences between the two groups in terms of age ( 22.40 + /- 4.21 vs 22.49 + /- 4.67 years ) , parity ( 72.77 % vs 70.35 % primi ) , type of eclampsia ( 84.65 % vs 85.42 % antepartum eclampsia ) , number of convulsions ( 5.30 + /- 3.26 vs 5.48 + /- 3.32 times ) , gestational age ( 35.65 + /- 3.37 vs 35.13 + /- 3.26 weeks ) , systolic blood pressure ( 153.19 + /- 20.19 vs 154.17 + /- 22.32 mmHg ) , diastolic blood pressure ( 106.23 + /- 13.84 vs 105.60 + /- 12.88 mmHg ) , proteinuria ( 70.80 % vs 72.36 % had > + proteinuria ) and Glasgow Coma Scale ( GCS ) ( 73.26 % vs 75.88 % > 8) for the loading and st and ard regime groups . There were also no differences between the two groups in mean fit and treatment interval ( 6.88 + /- 5.26 vs 7.12 + /- 4.29h ) , fit and delivery interval ( 11.35 + /- 10.22 vs 11 + /- 6.69h ) and return of consciousness ( 10.94 + /- 8.29 vs 11.24 + /- 8.37h ) . The recurrent convulsion rate was almost the same in both the groups ( 3.96 % in loading vs 3.51 % in st and ard regime , P > 0.05 ) . Case fatality rate was 4.45 % and 5.02 % in loading and st and ard regime groups , respectively ( P > 0.05 ) . CONCLUSION Only loading dose of MgSO4 can control convulsion in eclampsia and it is as effective as st and ard regime OBJECTIVES The purpose of this study was to determine the effect of a 6 gm intravenous bolus of magnesium sulfate on maternal brain blood flow velocity waveforms in patients with preeclampsia . STUDY DESIGN Twelve patients with preeclampsia were r and omized to two groups and studied with Doppler ultrasonography before and immediately after infusion of either a 6 gm intravenous loading dose of magnesium sulfate or a placebo . The middle cerebral , common carotid , and internal carotid arteries were studied . RESULTS Magnesium sulfate significantly reduced the pulsatility index in the middle cerebral artery ( change in pulsatility index = -0.16 + 0.09 ) when compared with the placebo ( change in pulsatility index = -0.02 + 0.06 ) , p = 0.01 . There were no significant changes in the Doppler indexes of the carotid vessels . CONCLUSIONS These data suggest that magnesium sulfate vasodilates the smaller-diameter intracranial vessels distal to the middle cerebral artery and may exert its main effect in the prophylaxis and treatment of eclampsia by relieving cerebral ischemia Although magnesium sulfate has been a traditional or st and ard treatment for severe preeclampsia and eclampsia to prevent convulsions , its efficiency has always been in doubt and its induced side‐effects also make it controversial for use . In this study , 64 patients , diagnosed with severe preeclampsia , were r and omized into group I ( 34 patients ) managed with MgS04 , and group II ( 30 patients ) managed without MgS04 . There were no occurrences of eclampsia in either group . Although there was no statistical significance in the final delivery method , group I had a higher rate in cesarean section , in which most were significantly due to fetal distress ( p<0.05 ) . Furthermore , group I had significantly more babies with poor apgar score than group II ( p = 0.019 ) . During the reatment period for those with a gestational age of less than 34 weeks , there were two patients with abruptio placentae in group 1 and the treatment periods were noted to be longer in group II than in group I. From the results of monitoring serum magnesium level in group I , when therapeutic level was achieved , magnesium sulfate induced great discomfort which might have led to the deterioration of the patients ' condition . According to this study , magnesium sulfate 's minimal efficiency . and its adverse side‐effects , also make magnesium sulfate a poor choice in the management of preeclampsia . Therefore , because of our poor underst and ing of the etiology of preeclampsia , suitable management should be undertaken without magnesium sulfate . Improvement of the patient 's pathophysiological condition or termination of pregnancy as early as possible , is recommended OBJECTIVE : To determine whether women receiving 12-hour and 24-hour postpartum magnesium sulfate ( MgSO4 ) therapy for mild preeclampsia have differing clinical courses . METHODS : Consenting women with suspected mild preeclampsia were r and omly assigned to12 hours or 24 hours of MgSO4 postpartum therapy . Treatment was continued after the assigned time period if there was evidence of severe preeclampsia . The frequency of progression to severe disease and other outcomes were compared between study groups using the Fisher exact , & khgr;2 , and Student t tests where appropriate . RESULTS : Between January 2001 and August 2004 , 200 women were enrolled . The 12-hour and 24-hour groups were similar in age , parity , delivered gestational age , anesthesia , and mode of delivery , as well as for proteinuria and blood pressure . In the 12-hour group , MgSO4 treatment was extended in seven women ( 6.9 % ) for progression to severe disease versus one ( 1.1 % ) in the 24-hour group ( P=.07 ) . Women who developed severe disease had higher blood pressures at the first prenatal visit ( 140/78 versus 122/69 , P≤.02 for systolic and diastolic pressures ) , at the time of r and omization ( 152/88 versus 135/78 , P≤.03 for systolic and diastolic pressures ) , and were more likely to have insulin-requiring diabetes ( 27.3 % versus 4.4 % , P=.03 ) . No 12-hour patients required treatment beyond 24 hours postpartum . There were no seizures , MgSO4 toxicity , or intolerance in either group . CONCLUSION : Twelve hours of postpartum MgSO4 therapy for mild preeclampsia is associated with infrequent disease progression and a clinical course similar to that with 24-hour therapy . Patients with chronic hypertension and insulin-requiring diabetes are at risk for progression to severe disease postpartum . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00344058 LEVEL OF EVIDENCE : Objectives : Although magnesium is now the drug of choice for the prevention of eclamptic seizures only few studies have evaluated whether magnesium may reduce blood pressure in pregnancies complicated with hypertension . Methods : A total of 33 patients with pregnancy-induced hypertension were r and omized to either magnesium or methyldopa treatment . Of these 16 received magnesium and 17 methyldopa . The treatment comprised a 48-hour magnesium infusion followed by oral magnesium tablets until 3 days after delivery or 250 mg methyldopa 4 times a day in a similar period . Results : Patients treated with magnesium had 1 day after inclusion a statistically significantly lower systolic blood pressure compared to the level in the methyldopa group ( 138.1 ± 11 vs. 147.6 ± 11 mm Hg ; p < 0.05 ) , but no difference was observed in diastolic blood pressure ( 92.0 ± 6.6 vs. 96.0 ± 10.1 mm Hg ; NS ) . From the 5th day of inclusion and until delivery both systolic and diastolic blood pressure were significantly lower in the magnesium group ( p < 0.05 ) . Including all blood pressure measurements in a single analysis showed that both systolic ( 138 ± 13 vs. 148 ± 15 mm Hg ; p < 0.0001 ) and diastolic ( 92 ± 10 vs. 94 ± 10 mm Hg ; p < 0.05 ) blood pressure were lower in the magnesium group compared to the methyldopa group . There was no difference between the two groups regarding gestational age at delivery , birth weight , Apgar scores and pH in umbilical cord blood . Conclusion : This preliminary study demonstrates that magnesium treatment lowers blood pressure in pregnancies complicated with hypertension . The effect is without any adverse effect on maternal and neonatal well-being Eclampsia remains an important cause of maternal mortality throughout the world . Although it has long been st and ard practice to use an anticonvulsant for the care of women with eclampsia , the choice .of agent has been controversial for more than 70 years . This situation changed recently with the publication of the Collaborative Eclampsia Trial , involving nearly 1700 women with eclampsia ' . In this study , roughly half the women were r and omised to receive either magnesium sulphate or diazepam , and the other half were r and omised to either magnesium sulphate or phenytoin . In the diazepam arm of the trial , women allocated magnesium sulphate had a 52 YO lower risk of recurrent convulsions ( 95 YO CI 64 % to 37 % ) than those on diazepam . In the phenytoin arm , women allocated magnesium had a 67 YO lower risk of recurrent convulsions ( 95 YO CI 79 YO to 47 % ) than those on phenytoin . There is now , for the first time , compelling evidence in favour of magnesium sulphate , rather than diazepam or phenytoin , for the treatment of women with eclampsia . Although magnesium sulphate is already part of routine clinical practice in some parts of the ~ o r l d ~ ~ ~ , in others it is rarely used or not available . For example , only 2 % of UK obstetricians said they used it in a recent survey4 , and for the trial magnesium sulphate had to be imported into Ghana , Ug and a and Zimbabwe , as it was not available locally . This suggests that many clinicians , both in the UK and elsewhere , will now be facing the challenges of first getting access to a drug they have not previously needed , and then of introducing it into their clinical management of a condition that they see only very rarely . As the evidence to support the use of magnesium sulphate for women with eclampsia comes from this recent study it is important that , as far as possible , the way in which magnesium sulphate was administered and its safety monitored within the trial are reflected in clinical practice . There were two separate regimens ( see below ) for giving magnesium sulphate , and clinicians at each centre chose which they would use . Women were allocated to an anticonvulsant by opening the next in a series of sealed treatment packs , a system which also has implication s for routine clinical practice A r and omized clinical trial was design ed to determine whether there are clinical ly demonstrable advantages of phenytoin over magnesium sulfate in preeclamptic patients because of the latter drug 's uterine relaxant properties . An intravenous infusion , immediately after r and omization , of either phenytoin or magnesium sulfate , with subsequent measurement of serum concentrations and maintenance of therapeutic levels was given to 103 preeclamptic and two eclamptic women . Observed were the rate of cervical dilation during active labor and change in hematocrit between predelivery and 24-hour postdelivery values and the incidence of side effects ascertained by interview . Compared with those receiving magnesium sulfate , patients receiving phenytoin had more rapid cervical dilation ( 3.3 cm/hr versus 1.5 cm/hr , p = 0.016 ) and a smaller fall in hematocrit after delivery ( -4.7 % versus -7.6 % , p = 0.034 ) . A significantly lower incidence of hot flushes ( 15 % versus 46 % , p < 0.005 ) and a trend toward less dyspnea and weakness were reported by phenytoin-treated patients . Our phenytoin regimen produced acceptable serum phenytoin levels ( 10 to 25 micrograms/ml ) in 96 % of patients It has been accepted that pre-eclampsia be treated with magnesium sulfate as the drug of choice . In recent years , phentolamine has been used to treat pre-eclampsia . The objective of this clinical controlled study was to observe the efficacy and effect of these two drugs on the mother and fetus in treating the women with preeclampsia . Eighty-four women with pre-eclampsia admitted into our hospital from June 1994 to June 1996 were enrolled . Their gestational age was 34]42 weeks . Diagnosis was made based on criteria in w x an article in Obstetrics and Gynecology , 3rd ed . 1 . Ž Course of disease the time from onset of disease . to admission was 1 day minimum and 20 days maximum , average 12.5 days . These patients were divided into two groups r and omly : 43 cases The effects of magnesium were compared with those of placebo in a r and omized double‐blind controlled study of 58 patients with pregnancy‐induced hypertension , of whom 27 received magnesium and 31 placebo . Twenty patients in each group were nulliparas . The treatment comprised 48 h of either intravenous magnesium or placebo infusion followed by daily oral magnesium or placebo tablets until one day after delivery . Magnesium supplementation significantly reduced maternal mean arterial blood pressure ( MAP ) . The gestational age at delivery was the same in both groups , whereas the relative fetal birth weight among nulliparas was reduced in the placebo group . Unbalanced analyses of variance suggested an influence of magnesium supplement on birth weight . The infants in the magnesium supplemented group spent fewer days in the neonatal intensive care unit . There were no perinatal deaths . Magnesium appeared to be beneficial in the management of pregnancy‐induced hypertension . The better outcome associated with magnesium supplementation may not have been due to reduction of MAP and further studies are needed to clarify whether magnesium influences birth weight OBJECTIVE The purpose of this study was to determine whether magnesium sulfate given for prevention of eclampsia affected labor outcomes compared with phenytoin , which is not known to impede uterine activity when given in anticonvulsant doses . STUDY DESIGN Secondary analysis was performed of a study of women with pregnancy-induced hypertension who were admitted for delivery and r and omly assigned to receive either magnesium sulfate or phenytoin for eclampsia prophylaxis . Nulliparous women with a singleton pregnancy in cephalic presentation at term were selected for analysis in an effort to limit the influence of confounding variables such as preterm birth and malpresentations on labor management and outcomes . Similarly , women who had severe preeclampsia and who received labor epidural analgesia were excluded . RESULTS A total of 2138 women were r and omized to receive magnesium sulfate or phenytoin in the primary study . A total of 905 nulliparous women met the inclusion criteria for this secondary analysis ; 480 had been r and omized to phenytoin and 425 were given magnesium sulfate . The two groups were similar demographically . Labor outcomes such as ( 1 ) oxytocin stimulation , ( 2 ) admission-to-delivery intervals , ( 3 ) prolonged second-stage labor , ( 4 ) forceps delivery , and ( 5 ) cesarean delivery were not affected by maternal treatment with magnesium sulfate . CONCLUSION Compared with phenytoin , magnesium sulfate given for intrapartum treatment of pregnancy-induced hypertension does not significantly affect labor outcomes OBJECTIVES Our purpose was to determine the effect of a 6 gm intravenous bolus of magnesium sulfate on maternal retinal blood flow velocity waveforms in patients with preeclampsia . STUDY DESIGN Twenty-two patients were r and omized to two groups and were studied with color flow Doppler before and immediately after infusion of either 6 gm of magnesium sulfate or placebo . The central retinal and posterior ciliary arteries were studied . RESULTS Magnesium sulfate significantly reduced the pulsatility index ( p < 0.005 ) in both vessels ( change in pulsatility index = 0.26 + /- 0.23 for central retinal and -0.22 + /- 0.15 for posterior ciliary ) when compared with placebo ( change in pulsatility index = 0.02 + /- 0.10 for central retinal and -0.03 + /- 0.09 for posterior ciliary ) . CONCLUSIONS These data suggest that magnesium sulfate dilates the vessels distal to the central retinal and posterior ciliary arteries . Changes in pulsatility index in the retinal arteries may be indicative of similar changes in other cerebral vessels Patients with severe pre-eclampsia were r and omised to receive magnesium sulphate according to an intramuscular ( IM ) ( N = 9 ) or an intravenous ( i.v . ) ( N = 8) regimen . The IM regimen consisted of a loading dose of 14 g ( 4 g i.v . and 10 g IM ) followed by 5 g 4-hourly . Patients given the IV regimen received a 6 g i.v . loading dose followed by a maintenance infusion of 2 g/h . Clinical outcome , laboratory parameters and serum magnesium levels were recorded for both groups . There were no significant differences between groups with regard to clinical outcome of either mother or child . Similar average serum magnesium concentrations were produced by the regimens the only significant difference was that fluctuations in magnesium levels were greater with the IM than the i.v . regimen . None of the patients had seizures despite levels mostly below 2 mmol/l Eclampsia remains a rare , but serious , complication of pregnancy , estimated to complicate around 1 in 2000 deliveries in Europe and other developed countries ( Douglas & Redman 1992 ) , and from 1 in 100 to 1700 deliveries in developing countries ( Crowther 1985 ; WHO lnternational Collaborative Study of Hypertensive Disorders of Pregnancy 1988 ) ; eclampsia is associated with 10 % of maternal deaths and approximately 50000 women die each year having had an eclamptic convulsion ( Duley 1992 ) . Much of the recent debate about management of women with eclampsia has focused on control of convulsions . Anticonvulsants are given to prevent the first fit in women who have fulminating pre-eclampsia and to prevent further convulsions in women who already have had an eclamptic fit . Although these indications are related , women who have pre-eclampsia are likely to be less sick than those with eclampsia . The potential for benefit or for harm will , therefore , be different , and the effectiveness of anticonvulsants should be evaluated separately for these two situations . For well over half a century , magnesium sulphate has been advocated for the care of women with pre-eclampsia and eclampsia , yet its use remains controversial ( Donaldson 1992 ) . In the past , the lack of a sound hypothesis for the mechanism by which magnesium sulphate might act as an anticonvulsant has contributed to this . Recent plausible suggestions are that it may act by vasodilatation and subsequent reduction of cerebral ischaemia ( Belfort & Moise 1992 ) ; an alternative is by blocking some of the neuronal damage associated with cerebral ischaemia ( Goldman & Finkbeiner 1988 ) . Reflecting ongoing uncertainty about its role , use of magnesium sulphate continues to vary enormously . In the United States , for example , magnesium sulphate is the anticonvulsant of choice for women with either eclampsia or pre-eclampsia ( Consensus Report 1990 ) , while in the United Kingdom it is used by only 2 % of obstetricians ( Hutton et al. 1992 ) . What is the evidence that magnesium sulphate given to women with either pre-eclampsia or eclampsia does more good than harm ? The popularity of . magnesium sulphate in North America ( and elsewhere ) is largely based on reports of a few hundred women with eclampsia who were treated with magnesium sulphate ( Pritchard et al. 1984 ) . Whilst sometimes impressive in the number of women included , none of these reports included any form of comparison or control group . Without comparison , it is impossible to know whether the good or bad outcome for the women was due to magnesium sulphate or to a combination of other factors , such as the severity of disease , health status of the women , or to additional interventions . The effectiveness of an intervention , such as magnesium sulphate , is best evaluated by systematic review of all relevant r and omised trials . In the perinatal field , a system for preparing and maintaining review s of the effects of health care already exists ( Cochrane Pregnancy and Childbirth Data base 1993 ) . The evidence presented here is derived from review s published on this data base Objective : To study effects of magnesium sulfate ( MgSO4 ) on prostacyclin ( PGI2 ) and thromboxane A2 ( TXA2 ) levels in women with severe preeclampsia during antepartum and postpartum periods . Methods : Women with severe preeclampsia were r and omized into two groups . Patients in Group A were continuously infused with MgSO4 for 24 hours postpartum . In Group B , MgSO4 administration was discontinued when urinary output was of ≥100 ml/hr for 2 consecutive hours . Patient demographic data were collected . Venous blood was drawn at time of MgSO4 administration and 24 hours after delivery . Plasma levels of 6-keto-PGF1α and TXB2 , stable metabolites of PGI2 and TXA2 , were measured by enzyme-linked immunosorbent assay ( ELISA ) . Data are presented as mean ± SE , and analyzed by paired t-test . Results : A total of 50 patients were recruited , with 27 in Group A and 23 in Group B. There were no statistical differences for demographic data between the two groups with regards to maternal age ; gestational age ; systolic and diastolic blood pressures at admission , 12 hours postpartum , and 24 hours postpartum ; and mode of delivery . Platelet counts were all within the normal range at the time of enrollment . MgSO4 was administered for an average of 10 hours postpartum in Group B. Maternal blood pressures returned to normal or close to normal levels in both groups at 24 hours postpartum . 6-keto PGF1α levels were significantly decreased 24 hours after delivery compared with the levels at enrollment in both groups , ( Group A : 98 ± 13 vs. 180 ± 28 pg/mL ; Group B : 142 + 17 vs. 194 ± 31 pg/mL , p < 0.05 , respectively ) . However , there was no difference detected between the two groups . TXB2 levels were not different between group A and Group B at the time of enrollment , 38 ± 9 vs. 33 ± 8 pg/mL , and 24 hours postpartum , 26 ± 5 vs. 25 ± 3 pg/mL , respectively . Conclusions : Administration of MgSO4 does not affect prostacyclin and thromboxane levels in the maternal circulation in women with preeclampsia during antepartum and postpartum periods . We speculate that a higher level of prostacyclin before delivery may reflect compensatory effects of this vasodilator to offset increased maternal blood pressure during pregnancy |
11,214 | 18,254,007 | This review does provide some limited evidence from both short- and long-term studies that aerobic or anaerobic physical training has a positive effect on primary outcomes ( exercise capacity , strength and lung function ) but improvements are not consistent between studies .
Physical training is already part of the care package offered to most people with cystic fibrosis and there is a lack of evidence to actively discourage this .
The benefits obtained from including physical training in a package of care may be influenced by the type of training programme . | BACKGROUND Physical training may form an important part of the care package for people with cystic fibrosis .
OBJECTIVES To determine whether a prescribed regimen of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training . | STUDY OBJECTIVE Exercise has the potential to improve the ability of a patient with cystic fibrosis ( CF ) to cope with the physical dem and s of everyday life , and may improve prognosis . The purpose of this study was to compare the effects of a home-based , semi-supervised , upper-body strength-training regimen with a similarly structured aerobic training regimen . DESIGN Data were collected during a 1-year r and omized clinical trial . SETTING Counselors conducted in-home visits with the participants once per week for the first 8 weeks followed by monthly visits for the remainder of the study . PATIENTS Sixty-seven patients with CF , aged 8 to 18 years , participated in the trial . INTERVENTION Participants in both exercise conditions were encouraged to exercise at least three times per week for 1 year . Each child in the aerobic group was given a stair-stepping machine , and each child in the upper-body strength training group was given an upper-body-only weight-resistance machine . MEASURES AND RESULTS Aerobic fitness , pulmonary function , quality of life , and strength were measured at baseline , at 6 months , and at 12 months . Strength training increased the maximum weight lifted for biceps curls significantly more than aerobic training ( p < 0.02 ) . However , this differential did not remain significant after control for increase in height . Both training procedures were associated with increased strength ( p < 0.002 ) and physical work capacity ( PWC ) [ p < 0.033 ] . CONCLUSIONS We concluded that strength and aerobic training may increase upper-body strength , and that both types of training may increase PWC for children with CF . Future trials should be conducted with no-training control subjects and larger sample s to increase statistical power BACKGROUND Children 's physical activity patterns are characterized by short-term anaerobic activities . Anaerobic exercise performance in children with cystic fibrosis ( CF ) has received little attention compared to aerobic performance . This study investigated the effects of anaerobic training in children with CF . DESIGN AND METHODS Twenty patients were r and omly assigned to the training group ( TG ) [ 11 patients ; mean ( + /- SD ) age , 13.6 + /- 1.3 years ; mean FEV(1 ) , 75.2 + /- 20.7 % predicted ] or the control group ( CG ) [ 9 patients ; mean age , 14.2 + /- 2.1 years ; FEV(1 ) , 82.1 + /- 19.1 % predicted ] . The TG trained 2 days per week for 12 weeks , with each session lasting 30 to 45 min . The training program consisted of anaerobic activities lasting 20 to 30 s. The control subjects were asked not to change their normal daily activities . Body composition , pulmonary function , peripheral muscle force , habitual physical activity , aerobic and anaerobic exercise performance , and quality of life were reevaluated at the end of the training program , and again after a 12-week follow-up period . RESULTS Patients in the TG significantly improved their anaerobic performance , aerobic performance , and quality of life . No significant changes were seen in other parameters , and no improvements were found in CG . After the follow-up period , only anaerobic performance and quality of life in TG were significantly higher compared to pretraining values . CONCLUSIONS Anaerobic training has measurable effects on aerobic performance ( although not sustained ) , anaerobic performance , and health-related quality of life in children with CF . Therefore , anaerobic training could be an important component of therapeutic programs for CF patients Bronchial hygiene therapy is a st and ard part of the treatment of patients with cystic fibrosis ( CF ) . Coughing alone promotes sputum expectoration and is probably the primary effective component of st and ard bronchial hygiene therapy . The purpose of this study was to determine whether substituting regular exercise , which also promotes coughing , for two of three daily bronchial hygiene treatments would affect the expected improvements in pulmonary function and exercise response in hospitalized patients with CF . Seventeen patients with CF hospitalized ( means length of stay = 13.0 + /- 2.6 days ) for an acute exacerbation of their pulmonary disease participated in the study . The patients were r and omly assigned to either a group that participated in two cycle ergometer exercise sessions and one bronchial hygiene treatment session per day ( EX Group [ n = 9 ] ) or a group that participated in three bronchial hygiene treatment sessions per day ( PD Group [ n = 8 ] ) . Pulmonary functions and responses to a progressive , incremental cycle ergometer exercise test were measured on admission and before discharge . Bronchial hygiene therapy consisted of postural drainage , in six positions , with chest percussion and vibration . Therapeutic exercise was of moderate intensity and was individually adjusted based on the patient 's heart rate and arterial oxygen saturation response to the admission exercise test . Coughing was encouraged during and after all treatments . Pulmonary function and exercise response were significantly improved over the period of hospitalization in both groups ; the improvements were the same in the two groups . These results indicate that , in some hospitalized patients with CF , exercise therapy may be substituted for at least part of the st and ard protocol of bronchial hygiene therapy Background : Short term studies of exercise training have shown benefits in cystic fibrosis . Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient . The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period . Methods : Subjects were r and omised to undertake three sessions per week of upper and lower body exercise based on individualised preferences ( n = 30 ) or to a control group ( n = 18 ) . They were evaluated at baseline and at 12 months . The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing . Secondary outcome measurements were heart rate and pulmonary function . Results : For leg exercise , significant differences were seen at 12 months between the active and control groups in the mean ( SE ) change in blood lactate levels ( −0.38 ( 0.23 ) mmol/l v 0.45 ( 0.25 ) mmol/l , p<0.05 ) and heart rate ( −4.8 ( 2.5 ) bpm v 3.4 ( 2.5 ) bpm , p<0.05 ) , confirming a training effect . For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity ( 46 ( 72 ) ml v −167 ( 68 ) ml , p<0.05 ) . Conclusions : A training effect , as measured by a reduction in lactate levels and heart rate , can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis . A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis The aim of this study was to compare aerobic and resistance training in children with cystic fibrosis ( CF ) admitted to hospital with an intercurrent pulmonary infection with a control group . The subjects were r and omized into three groups on the first day of admission . The fat-free mass ( FFM ) was calculated , using the skin fold thickness from four sites ( biceps , triceps , subscapular , and iliac crest ) . Pulmonary function tests were performed within 36 hr of admission and repeated on discharge from the hospital , and again at 1 month after discharge . All subjects performed an incremental treadmill exercise test , using a modified Bruce protocol . Lower limb strength was measured using a Cybex dynamometer . An assessment of quality of life was made using the Quality of Well Being Scale , as previously reported . Activity levels were measured using a 7-day activity diary , and subjects also wore an accelerometer on their hips . There were no significant differences between the three groups in terms of disease severity , and length of stay in hospital . Subjects in all three groups received intravenous antibiotics and nutritional supplementation as determined by the physician . Children r and omized to the aerobic training group participated in aerobic activities for five sessions , each of 30-min duration , a week . The children r and omized to the resistance training group exercised both upper and lower limbs against a grade d resistance machine . Subjects in the control group received st and ard chest physiotherapy . Our study demonstrated that children who received aerobic training had significantly better peak aerobic capacity , activity levels , and quality of life than children who received the resistance training program . Children who received resistance training had better weight gain ( total mass , as well as fat-free mass ) , lung function , and leg strength than children who received aerobic training . A combination of aerobic and resistance training may be the best training program , and future studies to assess optimal training programs for CF patients are indicated Six girls and two boys with cystic fibrosis ( CF ) 10 - 13.5 years of age ( mean 11.5 years ) participated in a prescribed exercise program on a mini-trampoline , maximum 109 min/week , during 8 weeks . The training consisted of three short bouts of trampoline exercise . The CF children were divided into two groups . The first group was a control as the other group exercised on the trampoline and vice versa . Three patients in each group completed the study . Pulmonary and exercise tests were performed before and after the exercise/control periods . The pulmonary tests ( FVC , FEV1 , and PEFR ) showed minor changes during the exercise period , but a slight increase in FVC ( P less than 0.05 ) during the total time of the study was found . The two patients with more advanced lung disease improved their spirometric results during the training period . The maximal oxygen uptake ( VO2 max ) improved from 45 to 49 ml/kg/min ( P less than 0.025 ) during the exercise period . Trampoline exercise programs are suggested to supply other types of training to avoid monotony in the training for CF patients OBJECTIVES To evaluate the effects of a 3-year home exercise program on pulmonary function and exercise tolerance in mildly to moderately impaired patients with cystic fibrosis ( CF ) and to assess whether regular aerobic exercise is a realistic treatment option . STUDY DESIGN Seventy-two patients with CF ( 7 - 19 years ) were r and omly assigned to an exercise group ( a minimum of 20 minutes of aerobic exercise , at a heart rate of approximately 150 beats/min , 3 times weekly ) or a control group ( usual physical activity participation ) . Pulmonary function , exercise tolerance , clinical status , hospitalizations , and compliance with therapy were monitored during scheduled visits to the hospital 's CF clinic . RESULTS Sixty-five patients were included in the analyses . The control group demonstrated a greater annual decline in percent of predicted forced vital capacity compared with the exercise group ( mean slope + /- SD , -2.42 + /- 4.15 vs -0.25 + /- 2.81 ; P = .02 ) , with a similar trend for forced expiratory volume in 1 second ( -3.47 + /- 4.93 vs -1.46 + /- 3 . 55 ; P = .07 ) . Patients remained compliant with the exercise program over the study period . An improved sense of well-being was reported with exercise . CONCLUSIONS Pulmonary function declined more slowly in the exercise group than in the control group , suggesting a benefit for patients with CF participating in regular aerobic exercise . Consistent compliance with the home exercise program and a self-reported positive attitude toward exercise provide further evidence of the feasibility and value of including an aerobic exercise program in the conventional treatment regimen of patients with CF Exercise intolerance is common in cystic fibrosis ( CF ) . We examined the effects of a supervised three-month running program on exercise tolerance , pulmonary function , cardiorespiratory fitness ( peak oxygen consumption ) , and respiratory muscle endurance in CF patients . We studied 31 patients , 21 exercise and ten control , aged 10 to 30 years , with pulmonary involvement ranging from mild to severe . The exercise and control groups were not significantly different with respect to age , sex , pulmonary function , exercise tolerance , or cardiorespiratory fitness . After three months of physical conditioning , the exercise group had significantly increased exercise tolerance and peak oxygen consumption and significantly lower heart rates for submaximal work loads , while the nonexercising ( control ) group was unchanged in all these variables . The FEV1 decreased significantly in the control group . There were no other significant changes in pulmonary function in either the control or exercise group . Respiratory muscle endurance increased significantly in the exercise patients , and did not change in the control patients . There were no adverse effects of the program . The data suggest that a supervised running program can increase CF patients ' exercise tolerance and cardiorespiratory fitness , perhaps in part by increasing respiratory muscle tolerance . The effects of a much longer program deserve study |
11,215 | 19,413,906 | Genetic molecular markers were related to an increased risk of therapeutic failure . | Background An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by Plasmodium falciparum .
The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number . | We assessed the efficacy of trimethoprim/sulfamethoxazole ( TRM/SMX ) in vivo in relation to the frequency of dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) alleles in 45 Sudanese malaria patients . Plasma levels of TRM , SMX , and acetylsulfamethoxazole ( AcSMX ) were measured before treatment and at days 3 , 7 , and 14 or upon recrudescence to ascertain drug absorption . Forty patients ( 89 % ) had an adequate clinical response , one patient ( 2 % ) had an early treatment failure response , while four patients ( 8 % ) showed late treatment failure responses . Genotyping of merozoite surface protein 1 , MSP-1 , MSP-2 , and glutamate-rich protein before treatment and upon recrudescence showed that all recurring parasites were recrudescences . The plasma levels of TRM , AcSMX , and SMX indicated adequate drug absorption in all patients . This suggests parasite resistance as a cause of treatment failure . The presence of dhfr Ile 51 and Asn 108 alone or coupled with dhps Ala-436 among parasites that were cleared after treatment indicates that these alleles alone are insufficient to cause in vivo resistance . However , the presence of the triple mutant dhfr ( Ile-51/Arg-59/Asn-108 ) with the dhps Gly-437 genotype in all recurring infections , suggests the importance of codon 59 and 437 alleles in susceptibility to TRM/SMX . However , the number is too little to make firm conclusions Background In Malawi , there has been a return of Plasmodium falciparum sensitivity to chloroquine ( CQ ) since sulfadoxine-pyrimethamine ( SP ) replaced CQ as first line treatment for uncomplicated malaria . When used for prophylaxis , Amodiaquine ( AQ ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa . Here we compare the efficacy , safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria . Methodology and Findings 455 children aged 1–5 years were recruited into a double-blinded r and omised trial comparing SP to the three combination therapies . Using intention to treat analysis with missing outcomes treated as successes , and without adjustment to distinguish recrudescence from new infections , the day 28 adequate clinical and parasitological response ( ACPR ) rate for SP was 25 % , inferior to each of the three combination therapies ( p<0.001 ) . AQ+SP had an ACPR rate of 97 % , higher than CQ+SP ( 81 % ) and ART+SP ( 70 % ) , p<0.001 . Nineteen children developed a neutropenia of ≤0.5 × 103 cells/µl by day 14 , more commonly after AQ+SP ( p = 0.03 ) . The mutation pfcrt 76 T , associated with CQ resistance , was detected in none of the pre-treatment or post-treatment parasites . The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP , p = 0.002 . Conclusions The combination AQ+SP was highly efficacious , despite the low efficacy of SP alone ; however , we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment . This study confirms the return of CQ sensitivity in Malawi and importantly , shows no evidence of the re-emergence of pfcrt 76 T after treatment with CQ or AQ . Given the safety record of AQ when used as a prophylaxis , our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny . Trial Registration Controlled-Trials.com IS RCT To determine the predictive value of chloroquine ( CQ ) resistance markers in Senegal , Plasmodium falciparum DNA polymorphisms in pfmdr1 and pfcrt were examined in relation to clinical outcome . Despite CQ treatment , 17 % of patients had parasitemia after 28 days . Examination of molecular markers of CQ resistance revealed that 64 % of all isolates had the T76 resistant allele at the pfcrt locus , while 30 % carried the Y86 resistant allele at the pfmdr1 locus . The pfcrt T76 allele was present not only in all in vivo resistant isolates , 89 % of in vitro resistant isolates , but also in 35 % of in vitro sensitive isolates . The pfmdr1 N86Y polymorphism did not correlate with in vitro or in vivo CQ resistance . Our data suggest that the pfcrt T76 allele alone is required but not a sufficient predictor for in vivo CQ resistance Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria ( artesunate+sulfadoxine-pyrimethamine [ AS+SP ] in the north , artesunate+amodiaquine [ AS+AQ ] in the south ) . In 2003 , we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated , seasonally endemic Nuba Mountains region ( the first study of AS combinations in southern Sudan ) . We also analysed pre-treatment blood sample s for mutations at the P. falciparum chloroquine transporter ( Pfcrt ) gene ( associated with CQ resistance ) , and at the dihydrofolate reductase ( Dhfr ) gene ( associated with pyrimethamine resistance ) . Among 161 r and omized children under 5 years , PCR-corrected cure rates after 28 days were 91.2 % ( 52/57 , 95 % CI 80.7 - 97.1 ) for AS+SP and 92.7 % ( 51/55 , 95 % CI 82.4 - 98.0 ) for AS+AQ , with equally rapid parasite and fever clearance . The Pfcrt K76 T mutation occurred in 90.0 % ( 144/160 ) of infections , suggesting CQ would work poorly in this region . Overall , 82.5 % ( 132/160 ) carried mutations at Dhfr ( N51I , C59R or S108N , but not I164L ) , but triple mutants ( more predictive of in vivo SP failure ) were rare ( 3.1 % ) . CQ use should be rapidly discontinued in this region . SP resistance may propagate rapidly , and AS+AQ is likely to be a better long-term option , provided AQ use is limited to the combination Plasmodium falciparum present in blood sample s collected before and 3 weeks after treatment with either pyrimethamine-sulfadoxine or chlorproguanil-dapsone was analyzed for variants of the genes coding for the target enzymes of antifolate drugs , dihydrofolate reductase ( DHFR ) and dihydropteroate synthetase ( DHPS ) . Fragments of the genes were amplified by polymerase chain reactions , and variants were identified by specific restriction endonuclease digestion . Treatment with either drug combination selected for the variants Ile51 , Arg59 , and Asn108 of DHFR , which have been associated with in vitro resistance to pyrimethamine and cycloguanil . The genotype Ser436 , Gly437 , and Glu540 of DHPS was selected by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment , showing that a combination of these three variants is important for in vivo resistance to sulfadoxine in the area studied Sulfadoxine-pyrimethamine efficacy was determined with a 28-day follow-up in 97 children between 6 months and 15 years of age . The polymerase chain reaction (PCR)-corrected treatment failure was 8.2 % and the uncorrected was 21.6 % . The presence of the dihydrofolate reductase ( DHFR ) and dihydropteroate synthetase ( DHPS ) mutations linked to sulfadoxine-pyrimethamine resistance before and after treatment was determined by PCR-restriction fragment length polymorphism ( RFLP ) and by a fluorogenic PCR assay . Before treatment , the prevalence of the triple DHFR mutations was higher among the patients having had a recurrent parasitemia ( either recrudescence or new infection ; 28.6 % versus 9.3 % ) , although the difference was not significant ( P = 0.1 ) . The double mutation Ala-436/Gly-437 was observed in 67 % of sample s , whereas no Glu-540 mutation was found . After treatment , the triple DHFR mutation was found in 76.2 % of patients with recurrent parasitemia , recrudescence , and new infection alike . Such high prevalence of mutant parasites indicates that sulfadoxine-pyrimethamine should not be used as monotherapy BACKGROUND Chloroquine ( CQ ) resistance has reached high levels in Africa in recent years . Little is known about variations of resistance between urban and rural areas . OBJECTIVES To compare the rates of in vivo resistance to CQ and the prevalences of the main molecular marker for CQ resistance among young children from urban and rural areas in Burkina Faso . METHODS The current analysis used the frame of a r and omized controlled trial ( IS RCT N27290841 ) on the combination CQ-methylene blue ( MB ) ( n=177 ) compared to CQ alone ( n=45 ) in young children with uncomplicated malaria . We examined clinical and parasitological failure rates as well as the prevalence of the Plasmodium falciparum chloroquine resistance transporter gene ( pfcrt ) T76 mutation . RESULTS Clinical and parasitological failure rates of CQ-MB differed significantly between urban ( 70 % ) and rural areas ( 29 % , p<0.0001 ) . Likewise , CQ failure rates were higher in the urban setting . Matching this pattern , pfcrt T76 was more frequently seen among parasite strains from urban areas ( 81 % ) when compared to rural ones ( 64 % , p=0.01 ) . In the presence of parasites exhibiting pfcrt T76 , the odds of overall clinical failure were increased to 2.6-fold ( [ 1.33 , 5.16 ] , p(LR)=0.005 ) . CQ was detected at baseline in 21 % and 2 % of children from the urban and the rural study area , respectively ( p(Chi)=0.002 ) . CONCLUSION Even within circumscribed geographical areas , CQ efficacy can vary dramatically . The differences in the prevalence of pfcrt T76 and in CQ failure rates are probably explained by a higher drug pressure in the urban area compared to the rural study area . This finding has important implication s for national malaria policies This study examines the relationship between malaria treatment failure after sulfadoxine-pyrimethamine ( S-P ) chemotherapy and presence of mutations in the Plasmodium falciparum dihydropteroate synthase ( dhps ) and dihydrofolate reductase ( dhfr ) genes ( associated with resistance in vitro to S and P ) before treatment . In Kenya , 38 malaria patients in a holoendemic area , and 21 in an epidemic area , participated in the trial in 1997 - 98 . In the 2 areas , drug failure occurred in 76 % and 75 % of cases where any mutation in dhfr was seen ( positive predictive values 76 % and 75 % : P = 0.003 and 0.008 ) and an identical association was seen with dhfr Asn-108 . In the holoendemic area all occurrences of > or = 2 mutations in dhfr predicted drug failure . Only 3 instances were seen in the epidemic focus , but treatment failed in all . Only in the epidemic focus , 7 ( 88 % ) of 8 occurrences of > or = 1 mutations in dhps , and all occurrences of the Gly-437 allele of dhps , predicted failure . Association between mutations in dhps and mutations in dhfr was noted in the combined sites , irrespective of outcome . Although this makes the relationship of combined dhfr and dhps mutations to failure more difficult to interpret , it nevertheless supports S-P selection acting on both genes . In the holoendemic site , treatment success increased with age . In this location , acquired immunity may mask the impact of mutations in dhps , since sulfadoxine is a less effective treatment than pyrimethamine The 4-aminoquinolines chloroquine ( CQ ) and amodiaquine ( AM ) were used to treat Gambian children with uncomplicated falciparum malaria in a r and omized drug trial . Blood sample s were taken immediately before treatment ( day 0 ) , and at day 7 and day 28 after treatment . Sample s from those parasitologically positive at day 7 following treatment ( ' early positives ' ) and those positive at day 28 but negative at day 7 ( ' late positives ' ) have been studied by PCR followed by restriction enzyme digestion to determine the allelic status of the pfmdr 1 locus at the codon-86 position ( asparagine or tyrosine ) , previously associated with resistance to CQ . A significantly higher prevalence of the tyr-86 allele was observed in sample s taken immediately before treatment ( day 0 ) in the early positives group when compared with the late positives group . This suggests the tyr-86 allele contributes to drug resistance in the early positives group . This association remained significant for both CQ and AM groups , implying a common genetic basis of resistance . Predominance of the allele at day 7 is consistent with a strong selection in the first week following treatment . In the late positives group , a significantly higher prevalence of the tyr-86 allele was observed in the sample s at day 28 when compared with those at day 0 , suggestive of selection during the period day 7 to day 28 . Differences were observed in the extent of this selection in the CQ and AM groups . The sample s were genotyped at 3 unlinked polymorphic loci . These analyses suggested that most parasites observed at day 7 were probably recrudescences whereas most of those at day 28 were reinfections A 28-day treatment trial was undertaken , to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers ( cg2 , pfmdr1 , and pfcrt ) that were previously linked to chloroquine resistance . In total , 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays . Of 81 patients ( 15.5 % prevalence ) who were positive by the assays and microscopy , 48 were eligible to participate in the 28-day trial . Nine patients defaulted . Chloroquine cured 54 % ( 95 % confidence interval , 45.8 - 61.8 ) of falciparum-infected patients . Of 18 ( 46 % ) patients with treatment failure , 13 ( 72 % ) experienced high- grade resistance . Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome . A mutation in PfCRT ( K76 T ) was perfectly associated with in vivo chloroquine resistance . However , K76 T was also present in in vivo-sensitive isolates , which suggests that the presence of this mutation was necessary , but not sufficient , to predict in vivo outcome in this cohort Surveillance of molecular markers for key mutations in Plasmodium falciparum dihydrofolate reductase ( DHFR ) and dihydropteroate synthetase ( DHPS ) has been proposed as a means of predicting sulfadoxine/ pyrimethamine ( SP ) treatment outcomes in Africa . This study assessed the association between DHFR and DHPS mutations and st and ardized clinical outcomes in children treated with SP for uncomplicated malaria in Kampala , Ug and a. Two mutations ( DHFR Asn-108 and Ile-51 ) were too common to be useful predictors . Three other mutations ( DHFR Arg-59 , DHPS Gly-437 , and DHPS Glu-540 ) were associated with clinical treatment failure after 14 days , although associations were not significant . When follow-up was extended to 28 days and genotyping was used to distinguish recrudescence from new infections , associations were significantly strengthened . The presence of both the DHFR Arg-59 and DHPS Glu-540 mutations had the strongest association with clinical treatment failure ( odds ratio = 10.7 , P = 0.009 ) . These results support a previously proposed method of predicting clinical outcomes based on the prevalence of these two mutations A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine ( SP ) as first-line treatment for uncomplicated malaria in Tanzania . Children under five years ( n = 117 ) with clinical , uncomplicated malaria were r and omly allocated to st and ard treatments of either chloroquine ( CQ ) ( 25 mg/kg ) or SP ( 25 mg sulfadoxine and 1.25 mg pyrimethamine/kg ) . Patients were monitored for 28 days . Clinical recovery was achieved in 98 % ( n = 58 ) and 90 % ( n = 59 ) of the patients in the SP and CQ groups , respectively . Parasitologically , 14 % of the patients in the SP group and 51 % in the CQ group exhibited RII/RIII resistance . When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations , no relationships could be detected . There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups . Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance ( RII/RIII ) observed two years prior to the introduction of the drug as first-line treatment is of concern , especially considering the long half-lives of sulfadoxine and pyrimethamine ABSTRACT A total of 252 children were enrolled in a drug trial to assess the effect of minimal doses of sulfadoxine ( Sdx ) and pyrimethamine ( Pyr ) . Parasite sample s isolated from these patients were analyzed before and after treatment to investigate the level of drug-resistant strains . The parasite genes encoding dihydrofolate reductase ( DHFR ) and dihydropteroate synthase ( DHPS ) were assayed for point mutations that are associated with resistance against drugs . Before treatment , Pyrr genotypes of the DHFR gene were found in 42 % of all sample s , 8 % of the patients harbored a mixed parasite population and 50 % had a sensitive DHFR genotype . In terms of the DHPS gene , we found mutations in 45 % of the parasites . Twenty-four percent had a Ser436 mutation , and 26 % had a Gly437mutation . Recrudescent parasites were highly enriched for both Pyrr and Sdxr strains after treatment ( P < 0.001 and P = 0.029 , respectively ) Molecular assays for monitoring sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes . This study analyzed pretreatment dihydrofolate reductase ( DHFR ) and dihydropteroate synthase ( DHPS ) genotypes and treatment outcomes in a double-blind , placebo-controlled trial of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment for uncomplicated P. falciparum malaria . Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors . Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations ( the " quintuple mutant " ) were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure . The presence of a single DHFR mutation ( Arg-59 ) with a single DHPS mutation ( Glu-540 ) accurately predicted the presence of the quintuple mutant . If this model is vali date d in other population s , it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa The effectiveness of chloroquine or sulfadoxine-pyrimethamine administered with artesunate for treating uncomplicated falciparum malaria was assessed in 2 Vietnamese provinces where the sensitivity of parasites in vitro to conventional therapies had increased with the removal of drug pressure . In the province of Dac Lac , where potential malaria exposure begins at birth , 57 subjects ( mean age , 9.6 years ) were r and omized to receive artesunate-chloroquine ( group 1 ) or artesunate-sulfadoxine-pyrimethamine ( group 2 ) . In the province of Binh Phuoc , 66 nonimmune workers and their relatives ( mean age , 24.2 years ) were similarly r and omized . By day 28 of follow-up , > 96 % of Dac Lac patients and < 52 % of Binh Phuoc patients in group 1 and group 2 had an in vivo response that demonstrated sensitivity to therapy . PCR-confirmed cure rates paralleled in vivo results among patients in Binh Phuoc , but PCR results identified 9 ( 15.7 % ) of the Dac Lac patients as having experienced asymptomatic , su bmi croscopic recrudescences . In Dac Lac , pfcrt K76 T was near fixation , but infection with parasites with this mutation predicted recrudescence among group 1 patients in Binh Phuoc . Common pfdhfr mutations did not predict outcome in group 2 . The successful re introduction of conventional therapies in combination with artesunate depends on epidemiological and /or parasitological factors BACKGROUND The borders of Thail and harbour the world 's most multidrug resistant Plasmodium falciparum parasites . In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria , but substantial resistance developed within 6 years . A combination of artesunate with mefloquine now cures more than 95 % of acute infections . For both treatment regimens , the underlying mechanisms of resistance are not known . METHODS The relation between polymorphisms in the P falciparum multidrug resistant gene 1 ( pfmdr1 ) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 sample s from patients with falciparum malaria studied prospect ively over 12 years . pfmdr1 copy number was assessed by a robust real-time PCR assay . Single nucleotide polymorphisms of pfmdr1 , P falciparum chloroquine resistance transporter gene ( pfcrt ) and P falciparum Ca2 + ATPase gene ( pfATP6 ) were assessed by PCR-restriction fragment length polymorphism . FINDINGS Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine , and also to reduced artesunate sensitivity in vitro . In a Cox regression model with control for known confounders , increased pfmdr1 copy number was associated with an attributable hazard ratio ( AHR ) for treatment failure of 6.3 ( 95 % CI 2.9 - 13.8 , p<0.001 ) after mefloquine monotherapy and 5.4 ( 2.0 - 14.6 , p=0.001 ) after artesunate-mefloquine therapy . Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro , but not in vivo . INTERPRETATION Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria . RELEVANCE TO PRACTICE Multidrug resistant P falciparum malaria is common in southeast Asia , but difficult to identify and treat . Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance . In this study we show that increase in copy number of pfmdr1 , a gene encoding a parasite transport protein , is the best overall predictor of treatment failure with mefloquine . Increase in pfmdr1 copy number predicts failure even after chemotherapy with the highly effective combination of mefloquine and 3 days ' artesunate . Monitoring of pfmdr1 copy number will be useful in epidemiological surveys of drug resistance in P falciparum , and potentially for predicting treatment failure in individual patients |
11,216 | 28,052,652 | Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer .
Overall , agents that specifically target the vascular endothelial growth factor lig and or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors | Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers , their prognosis remains dismal .
Tumor angiogenesis plays a key role in cancer growth and metastasis , and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy .
In this systematic review , we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer .
Included studies aim ed to prospect ively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer . | BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline ) were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company Summary Background Cisplatin and fluoropyrimidine ( CF ) are st and ard first- line treatment in advanced gastric cancer , but no second-line treatment has yet been established . We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib ( S ) , and Oxaliplatin as second-line therapy . Methods Patients with progressive gastric adenocarcinoma after CF- first-line , ECOG 0–2 , and measurable disease were included . The primary objective was PFS . Treatment doses were Oxaliplatin 130 mg/m2/3 weeks and Sorafenib 800 mg/bid/d . Results We included 40 patients . CR was 2.5 % and SD was 47.2 % . Grade 3–4 toxic effects were neutropenia ( 9.8 % ) , thrombocytopenia ( 7.3 % ) , neurotoxicity ( 4.9 % ) and diarrhea ( 4.9 % ) . Median PFS was 3 months ( 95 % CI : 2.3–4.1 ) and median OS was 6.5 months ( 95 % CI : 5.2–9.6 ) . Time to progression ( TTP ) to first line therapy was a prognosis factor . Median OS was 9.7 months when time-to-progression during first-line chemotherapy was > 6 months and 5.6 m when it was < 6 months ( p = 0.04 ) . Conclusions Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis . The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe , but our results do not support the implementation of a phase III trial Summary Purpose . This phase II , open-label , multicenter study assessed the oral , multitargeted , tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy . Experimental design . Patients received sunitinib 50 mg/day on Schedule 4/2 ( 4 weeks on treatment , followed by 2 weeks off treatment ) . The primary endpoint was objective response rate ; secondary endpoints included clinical benefit rate , duration of response , progression-free survival ( PFS ) , overall survival ( OS ) , pharmacokinetics , pharmacodynamics , safety and tolerability , and quality of life . Results . Of 78 patients enrolled , most had gastric adenocarcinoma ( 93.6 % ) and metastatic disease ( 93.6 % ) . All were evaluable for safety and efficacy . Two patients ( 2.6 % ) had partial responses and 25 patients ( 32.1 % ) had a best response of stable disease for ≥6 weeks . Median PFS was 2.3 months ( 95 % confidence interval [ CI ] , 1.6–2.6 months ) and median OS was 6.8 months ( 95 % CI , 4.4–9.6 months ) . Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6 % and 29.4 % of patients , respectively , and the most common non-hematologic adverse events were fatigue , anorexia , nausea , diarrhea , and stomatitis . Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports . There were no marked associations between baseline soluble protein levels , or changes from baseline , and measures of clinical outcome . Conclusions . The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer , its role in combination with chemotherapy merits further study Background : This study aim ed to determine whether combination S-1 plus cisplatin ( CDDP ) therapy , the most widely used therapy for Japanese patients with advanced gastric cancer , and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment . Methods : Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were r and omised into two groups : TSU-68 plus S-1/CDDP ( group A ) and S-1/CDDP ( group B ) groups . Both patient groups received identical S-1 and CDDP dosages . TSU-68 was orally administered for 35 consecutive days . Group B patients received S-1 orally twice daily for three consecutive weeks , followed by intravenous CDDP on day 8 . The primary endpoint was progression-free survival ( PFS ) . Results : Median PFS periods were 208 and 213 days in groups A and B , respectively ( P=0.427 ) . Median survival periods for groups A and B were 497.0 and 463.5 days , respectively ( P=0.219 ) . No statistically significant differences were noted for PFS , survival or the adverse event ( AE ) incidence rate . All AEs were expected according to previous reports for TSU-68 , TS-1 , and CDDP . Conclusion : Combination therapy involving TSU-68 , S-1 , and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers . However , factors related to therapeutic efficacy should be investigated further BACKGROUND Peri-operative chemotherapy and surgery is a st and ard treatment of localised oesophagogastric adenocarcinoma ; however , the outcomes remain poor . PATIENTS AND METHODS ST03 is a multicentre , r and omised , phase II/III study comparing peri-operative ECX with or without bevacizumab ( ECX-B ) . The primary outcome measure of phase II ( n = 200 ) was safety , specifically gastrointestinal ( GI ) perforation rates and cardiotoxicity . RESULTS Two hundred patients were r and omised between October 2007 and April 2010 . Ninety-one/101 ( 90 % ) ECX and 86/99 ( 87 % ) ECX-B patients completed pre-operative chemotherapy ; 7 ECX and 9 ECX-B patients stopped due to toxicity . Gastrointestinal perforations ( 3 ECX , 1 ECX-B ) , cardiac events ( 1 ECX , 4 ECX-B ) and venous thromboembolic events ( VTEs , 8 ECX , 7 ECX-B ) were uncommon . Arterial thromboembolic events ( ATEs , myocardial infa rct ion ( MI ) or cerebrovascular accident ) were more frequent with ECX-B ( 5 versus 1 with ECX ) . Delayed wound healing , anastomotic leaks and GI bleeding rates were similar . More asymptomatic left ventricular ejection fraction ( LVEF ) falls ( ≥15 % and /or to < 50 % ) occurred with ECX-B ( 21.2 % versus 11.1 % with ECX ) . Clinical ly significant falls ( ≥10 % to below lower limit of normal , LLN ) occurred in ( 15.3 % ) and ( 8.9 % ) respectively , with no associated cardiac failure ( median 22 months follow-up ) . CONCLUSIONS Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes We design ed a single-arm , open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx ( capecitabine and oxaliplatin ) in metastatic /recurrent advanced gastric cancer ( AGC ) patients . Previously untreated AGC patients received capecitabine ( 850 mg/m2 bid , day 1–14 ) plus oxaliplatin ( 130 mg/m2 , day 1 ) in combination with pazopanib ( 800 mg , day 1–21 ) every three weeks . Treatment was continued until progression of the disease or intolerable toxicity was observed . In all , 66 patients were treated with pazopanib plus CapeOx . The median age of the patients was 51.5 years ( range , 23.0–77 ) , and the median ECOG performance status was 1 ( 0–1 ) . Among all 66 patients , one complete response and 37 partial responses were observed ( overall response rate , 62.4 % ; 95 % confidence interval ( CI ) , 45.7–73.5 % accounting for the 2-stage design of this trial ) . Stable disease was observed in 23 patients ( 34.8 % ) , revealing a 92.4 % disease control rate . The median progression free survival and overall survival were 6.5 months ( 95 % CI , 5.6–7.4 ) and 10.5 months ( 95 % CI , 8.1–12.9 ) , respectively . Thirty-four patients ( 51.5 % ) experienced a treatment-related toxicity of grade 3 or more . The most common toxicities of grade 3 or more were neutropenia ( 15.1 % ) , anemia ( 10.6 % ) , thrombocytopenia ( 10.6 % ) , anorexia ( 7.6 % ) , nausea ( 3.0 % ) , and vomiting ( 3.0 % ) . There were no treatment-related deaths . The combination of pazopanib and CapeOx showed moderate activity and an acceptable toxicity profile as a first-line treatment in metastatic / recurrent AGC patients ( Clinical Trials.gov NCT01130805 ) PURPOSE We evaluated the activity of regorafenib , an oral multikinase inhibitor , in advanced gastric adenocarcinoma . PATIENTS AND METHODS We conducted an international ( Australia and New Zeal and , South Korea , and Canada ) r and omized phase II trial in which patients were r and omly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease ( one v two ) and region . Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred . The primary end point was progression-free survival ( PFS ) . Final analysis included data to December 31 , 2014 . RESULTS A total of 152 patients were r and omly assigned from November 7 , 2012 , to February 25 , 2014 , yielding 147 evaluable patients ( regorafenib , n = 97 ; placebo , n = 50 ) . Baseline characteristics were balanced . Median PFS significantly differed between groups ( regorafenib , 2.6 months ; 95 % CI , 1.8 to 3.1 and placebo , 0.9 months ; 95 % CI , 0.9 to 0.9 ; hazard ratio [ HR ] , 0.40 ; 95 % CI , 0.28 to 0.59 ; P < .001 ) . The effect was greater in South Korea than in Australia , New Zeal and , and Canada combined ( HR , 0.12 v 0.61 ; interaction P < .001 ) but consistent across age , neutrophil-to-lymphocyte ratio , primary site , lines of chemotherapy , peritoneal metastasis presence , number of metastatic sites , and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen ( median , 5.8 months ; 95 % CI , 4.4 to 6.8 v 4.5 months ; 95 % CI , 3.4 to 5.2 ; HR , 0.74 ; P = .147 ) . Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression . Regorafenib toxicity was similar to that previously reported . CONCLUSION In this phase II trial , regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma . Regional differences were found , but regorafenib was effective in both regional groups . A phase III trial is planned Summary Introduction This study aim ed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor , v and etanib ( V ) , in combination with two chemotherapeutic agents , oxaliplatin ( O ) and docetaxel ( D ) in advanced gastroesophageal ( GE ) cancer . Methods This was a Phase I study ( NCT00732745 ) with a st and ard 3 + 3 dose escalation design . The primary aim was to determine the optimal dose of the combination of v and etanib and OD chemotherapy . Results Initial treatment for the first cohort consisted of oxaliplatin at 100 mg/m2 on day 1 , docetaxel at 35 mg/m2 on days 1 and 8 and v and etanib 100 mg PO daily of 21-day treatment cycles . As dose limiting toxicity ( DLT ) was reached in 2 out of 3 patients in cohort 1 ( one grade 3 and one grade 4 diarrhea with dehydration ) , 6 patients were treated then at dose level −1 ( O 80 mg/m2 on day 1 , D 30 mg/m2 on days 1 and 8 , V 100 mg PO daily days 1–21 ) in which no further DLTs were observed . This dose was established as maximum tolerated dose and is the recommended phase 2 dose . 8 out of 9 enrolled patients had adenocarcinoma . At dose level 1 , 1 of the 3 patients had a documented partial response and 2 patients had stable disease . At dose level −1 , 1 of 6 patients achieved a complete response , 2 of 6 patients had stable disease , and 3 of 6 patients had progressive disease . Conclusions V and etanib added to oxaliplatin and docetaxel showed manageable toxicity and limited activity in advanced GE cancer Summary Background To define maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) , and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer ( AGC ) patients . Methods Four dose-level combinations were tested in a st and ard 3 + 3 dose escalation design . Level 1 : sorafenib 400 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 2 : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 3 : sorafenib 800 mg/d , capecitabine 2,000 mg/m2/d , cisplatin 80 mg/m2 . Level 1A : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 60 mg/m2 . Results There were 1 DLT at Level 2 , and 2 DLTs at Level 3 ( Level 3 was MTD ) . Since the relative dose intensity ( RDI ) of sorafenib and capecitabine could not be maintained at Level 2 , Level 1A was newly investigated . As no DLT was observed and RDI remained above 80 % , Level 1A is the recommended dose for the next clinical trial . Objective response rate was 62.5 % ( 10 of 16 patients , 95 % CI ; 38.8–86.2 % ) . Median progression-free survival and overall survival were 10.0 months ( 95 % CI ; 7.4–13.8 ) and 14.7 months ( 95 % CI ; 12.0–20.0 ) , respectively . Conclusions Sorafenib 400 mg bid daily , capecitabine 800 mg/m2 bid ( days 1–14 ) , and cisplatin 60 mg/m2 ( day 1 ) is recommended for further development in AGC 4122 Background : Angiogenesis is essential for tumor growth and plays an important role in metastasis in gastrointestinal ( GI ) cancers . TEL is a highly selective and potent oral kinase inhibitor with activity against VEGFR family , PDGFR and KIT receptor tyrosine kinases . TEL has been studies in 250 pts in Phase 1 and Phase 1b studies . TEL0805 is a multicenter phase II study that administered TEL with X and P in previously untreated advanced gastric or GEJ cancer pts . METHODS From June 2009 to August 2010 , 48 pts were enrolled from the US and Spain . Treatment cycles were 21 days ( d ) : TEL 900 mg p.o . bid continuously , X 1,000 mg/m2p.o . bid D1 - 14 , P 80 mg/m2 D1 . RESULTS The majority ( 94 % ) of pts were metastatic ( 52 % with liver metastases ) . Tumor location was nearly equal between GEJ ( 54 % ) and gastric ( 46 % ) at presentation . 39 pts were evaluable for response per protocol ( PP ) . The ORR was 67 % ( CR 2.6 % , PR 64.1 % ) ; an additional 28.2 % of pts had SD as best response . Responses were observed independent of tumor location . The onset of response was rapid , median 49 d. The median PFS was 140 d ( range 46 to 341 + ) . The median OS has not been reached ( 20 pts censored PP ) . The most common toxicities were G1/2 fatigue or GI ; < 10 % of pts discontinued treatment due to TEL AEs . Sample s were available for PD in 28 patients . Reduction in plasma sVEGR2 levels up to 45 % from baseline was observed with a median of 26 % reduction in all participating pts . A statistically significant trend was observed between the degree of reduction in sVEGFR2 levels from baseline and clinical trial endpoints . Morphological changes in CT scans were noted that are consistent with potent anti-angiogenic activity . CONCLUSIONS TEL in combination with X and P achieved a rapid and sustained tumor regression in 2/3 of metastatic gastric and GEJ cancer pts regardless of tumor location , histology , or presence of liver mets . TEL demonstrated potent on target activity as demonstrated by the sVEGFR2 levels , which appear to correlate with clinical benefit and may provide a potential biomarker of activity . A global r and omized phase III study is planned BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Summary Progression-free survival ( PFS ) and time to progression ( TTP ) have been reported to correlate with overall survival ( OS ) in several types of cancers . To our knowledge , however , their use in the evaluation of new agents for AGC has not been investigated . We evaluated the potential of PFS and TTP to act as surrogates of OS in clinical trial setting s. R and omized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search . Correlations between PFS/TTP and OS were evaluated . Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis . The nonparametric Spearman rank correlation coefficient ( ρ ) between median PFS/TTP and OS was 0.70 ( 95 % CI , 0.59 to 0.82 ) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 ( 95 % CI , 0.68 to 0.92 ) . Correlation tended to be higher in trials reporting PFS ( ρ = 0.85 ; 0.72–0.97 ) than in those reporting TTP ( ρ = 0.60 ; 0.24–0.97 ) , trials in Non-Asian countries ( ρ = 0.80 ; 0.61–0.99 ) than Asia ( ρ = 0.67 ; 0.39–0.94 ) , trials in patients with measurable lesions only ( ρ = 0.91 ; 0.77–1.00 ) than in those including non-measurable lesions ( ρ = 0.71 ; 0.50–0.93 ) , albeit that none of these differences was significant . Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS . Further research is needed to clarify the surrogacy of PFS/TTP for OS or the role of PFS as the true end point in future r and omized clinical trials of chemotherapy for AGC BACKGROUND AND AIM East Asia has higher gastric cancer incidence and mortality rates than other regions . We present a subgroup analysis of East Asians in the positive study RAINBOW . METHODS Patients with advanced gastric or gastroesophageal junction adenocarcinoma previously treated with platinum and fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 of a 28-day cycle . RESULTS Of 665 intention-to-treat patients , 223 were East Asian . Median overall survival was 12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus paclitaxel ( hazard ratio : 0.986 , 95 % confidence interval : 0.727 - 1.337 , P = 0.929 ) . Median progression-free survival was 5.5 months for ramucirumab plus paclitaxel and 2.8 months for placebo plus paclitaxel ( hazard ratio : 0.628 , 95 % confidence interval : 0.473 - 0.834 , P = 0.001 ) . Objective response rates were 34 % for ramucirumab plus paclitaxel and 20 % for placebo plus paclitaxel . Grade ≥ 3 neutropenia ( 60 % vs 28 % ) and leukopenia ( 34 % vs 13 % ) were higher for ramucirumab plus paclitaxel . The rate of febrile neutropenia was low ( 4 % vs 4 % ) . Special interest adverse events included any grade bleeding/hemorrhage ( 55 % vs 25 % ) , proteinuria ( 27 % vs 7 % ) , and hypertension ( 22 % vs 2 % ) . CONCLUSIONS Ramucirumab plus paclitaxel significantly improves progression-free survival and response rate , with prolonged median overall survival and an acceptable safety profile in East Asians with advanced gastric cancer Background : In the phase III AVAGAST trial , the addition of bevacizumab to chemotherapy improved progression-free survival ( PFS ) but not overall survival ( OS ) in patients with advanced gastric cancer . We studied the role of Angiopoietin-2 ( Ang-2 ) , a key driver of tumour angiogenesis , metastasis and resistance to antiangiogenic treatment , as a biomarker . Methods : Previously untreated , advanced gastric cancer patients were r and omly assigned to receive bevacizumab ( n=387 ) or placebo ( n=387 ) in combination with chemotherapy . Plasma collected at baseline and at progression was analysed by ELISA . The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model . Logistic regression analysis was applied for correlations with metastasis . Results : Median baseline plasma Ang-2 levels were lower in Asian ( 2143 pg ml−1 ) vs non-Asian patients ( 3193 pg ml−1 ) , P<0.0001 . Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF . Baseline plasma Ang-2 correlated with the frequency of liver metastasis ( LM ) at any time : Odds ratio per 1000 pg ml−1 increase : 1.19 ; 95 % CI 1.10–1.29 ; P<0.0001 ( non-Asians ) and 1.37 ; 95 % CI 1.13–1.64 ; P=0.0010 ( Asians ) . Conclusions : Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM . Differences in Ang-2 mediated vascular response may , in part , account for outcome differences between Asian and non-Asian patients ; however , data have to be further vali date d. Ang-2 is a promising drug target in gastric cancer Background : Blockade of the vascular endothelial growth factor ( VEGF ) pathway shows evidence of activity in gastro-oesophageal ( GE ) and oesophageal cancer . We investigated the efficacy of sunitinib , a multikinase VEGF inhibitor , in patients with relapsed/refractory GE/oesophageal cancer . Methods : This was a single-stage Fleming phase II study . The primary end point was progression-free survival ( PFS ) at 24 weeks . If five or more patients out of a total of 25 were free of progressive disease at 24 weeks , sunitinib would be recommended for further study . Patients received sunitinib 37.5 mg orally daily and imaged every 6 weeks . Exploratory correlative analysis included serum growth factors , tumour gene expression and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) . Results : Twenty-five evaluable patients participated in the study . Progression-free survival at 24 weeks was 8 % ( n=2 patients ; confidence interval ( CI ) : 95 % 1.4–22.5 % ) , and the duration of best response for the patients was 23 and 72 weeks . Ten patients ( 42 % ) had stable disease ( SD ) for > 10 weeks . Overall response rate is 13 % . Median PFS is 7 weeks ( 95 % CI : 5.6–11.4 weeks ) and the median overall survival is 17 weeks ( 95 % CI : 8.9–25.3 weeks ) . Most common grade 3/4 toxicities included fatigue ( 24 % ) , anaemia ( 20 % ) thrombocytopenia ( 16 % ) , and leucopenia ( 16 % ) . No patients discontinued therapy due to toxicity . Serum VEGF-A and -C levels , tumour complement factor B ( CFB ) gene expression , and DCE-MRI correlated with clinical benefit , defined as SD or better as best response . Conclusion : Sunitinib is well tolerated but only a select subgroup of patients benefited . Serum VEGF-A and -C may be early predictors of benefit . On this study , patients with clinical benefit from sunitinib had higher tumour CFB expression , and thus has identified CFB as a potential predictor for efficacy of anti-angiogenic therapy . These findings need validation from future prospect i ve trials BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . Purpose This phase I trial evaluated the question of whether the st and ard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer , and assessed overall safety , pharmacokinetics , and preliminary antitumor activity of this combination . Material s and Methods Patients in dose level ( DL ) 1 received axitinib 5 mg twice a day ( days 1 to 21 ) with cisplatin 80 mg/m2 ( day 1 ) and capecitabine 1,000 mg/m2 twice a day ( days 1 to 14 ) in 21-day cycles . Maximum tolerated dose ( MTD ) was the highest dose at which ≤ 30 % of the first 12 patients experienced a dose-limiting toxicity ( DLT ) during cycle 1 . Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data . Results Three DLTs occurred during cycle 1 in three ( 25 % ) of the first 12 patients : ruptured abdominal aortic aneurysm , acute renal failure , and > 5 consecutive days of missed axitinib due to thrombocytopenia . DL1 was established as the MTD , since higher DL cohorts were not planned . Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension ( 36.4 % ) and decreased appetite and stomatitis ( 18.2 % each ) . Cisplatin/capecitabine slightly increased axitinib exposure ; axitinib decreased capecitabine and 5-fluorouracil exposure . Eight patients ( 36.4 % ) each had partial response or stable disease . Median response duration was 9.1 months ; median progression-free survival was 3.8 months . Conclusion In patients with advanced gastric cancer , st and ard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination . Adverse events were manageable PURPOSE The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival . To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer , AVAGAST included a prospect i ve , m and atory biomarker program . PATIENTS AND METHODS Patients with previously untreated , locally advanced or metastatic gastric cancer were r and omly assigned to bevacizumab ( n = 387 ) or placebo ( n = 387 ) in combination with chemotherapy . Blood and tumor tissue sample s were collected at baseline . Prespecified biomarkers included plasma vascular endothelial growth factor-A ( VEGF-A ) , protein expression of neuropilin-1 , and VEGF receptors-1 and -2 ( VEGFR-1 and VEGFR-2 ) . Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model . RESULTS Plasma was available from 712 patients ( 92 % ) , and tumor sample s were available from 727 patients ( 94 % ) . Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy . Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival ( hazard ratio [ HR ] , 0.72 ; 95 % CI , 0.57 to 0.93 ) versus patients with low VEGF-A levels ( HR , 1.01 ; 95 % CI , 0.77 to 1.31 ; interaction P = .07 ) . Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival ( HR , 0.75 ; 95 % CI , 0.59 to 0.97 ) versus patients with high neuropilin-1 expression ( HR , 1.07 ; 95 % CI , 0.81 to 1.40 ; interaction P = .06 ) . For both biomarkers , subgroup analyses demonstrated significance only in patients from non-Asian regions . CONCLUSION Plasma VEGF-A and tumor neuropilin-1 are strong biomarker c and i date s for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems Malignancies in the upper gastrointestinal ( UGI ) tract are amongst the most aggressive cancers and only few treatment options exist . We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab . The combination therapy could not be recommended in an unselected population of patients with chemo-refractory UGI cancer . However , a sub population of patients did benefit from the therapy . In this prospect ively planned biomarker study we investigated vascular endothelial growth factor A ( VEGF-A ) , VEGF receptor 2 ( VEGFR-2 ) and epidermal growth factor receptor ( EGFR ) by immunohistochemistry and KRAS mutation status detected by PCR as potential predictors of effect of therapy . High VEGF-A expression was correlated to longer overall survival ( HR : 0.8 , 95%CI : 0.7 - 0.9 ) and high VEGFR-2 expression to shorter progression free survival ( HR : 1.4 , 95%CI : 1.0 - 1.9 ) . EGFR expression and KRAS mutation status were not correlated to response or survival . We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab PURPOSE To evaluate the safety , maximum-tolerated dose ( MTD ) , pharmacokinetics ( PKs ) , pharmacodynamics , and preliminary anticancer activity of ramucirumab ( IMC-1121B ) , a fully human immunoglobulin G(1 ) monoclonal antibody targeting the vascular endothelial growth factor receptor (VEGFR)-2 . PATIENTS AND METHODS Patients with advanced solid malignancies were treated once weekly with escalating doses of ramucirumab . Blood was sample d for PK studies throughout treatment . The effects of ramucirumab on circulating vascular endothelial growth factor-A ( VEGF-A ) , soluble VEGFR-1 and VEGFR-2 , tumor perfusion , and vascularity using dynamic contrast-enhanced magnetic resonance imaging were assessed . Results Thirty-seven patients were treated with 2 to 16 mg/kg of ramucirumab . After one patient each developed dose-limiting hypertension and deep venous thrombosis at 16 mg/kg , the next lower dose ( 13 mg/kg ) was considered the MTD . Nausea , vomiting , headache , fatigue , and proteinuria were also noted . Four ( 15 % ) of 27 patients with measurable disease had a partial response ( PR ) , and 11 ( 30 % ) of 37 patients had either a PR or stable disease lasting at least 6 months . PKs were characterized by dose-dependent elimination and nonlinear exposure consistent with saturable clearance . Mean trough concentrations exceeded biologically relevant target levels throughout treatment at all dose levels . Serum VEGF-A increased 1.5 to 3.5 times above pretreatment values and remained in this range throughout treatment at all dose levels . Tumor perfusion and vascularity decreased in 69 % of evaluable patients . CONCLUSION Objective antitumor activity and antiangiogenic effects were observed over a wide range of dose levels , suggesting that ramucirumab may have a favorable therapeutic index in treating malignancies amenable to VEGFR-2 inhibition |
11,217 | 29,464,501 | The level of evidence identified for the use of probiotics in IBS was excellent in quality ; however , the evidence available for the use of probiotic interventions in CFS/ME was poor and limited .
There is currently insufficient evidence for the use of probiotics in CFS/ME patients , despite probiotic interventions being useful in IBS . | Gastrointestinal ( GI ) symptoms and irritable bowel ( IB ) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) .
The aim of this study was to conduct a systematic review of these symptoms in CFS/ME , along with any evidence for probiotics as treatment . | Background Chronic fatigue syndrome ( CFS ) presents a challenge for patients , health care providers , and health insurance groups because of its incapacitating nature , unknown cause , and poorly understood prognosis . We conducted a longitudinal population -based study to characterize the clinical course of CFS . Methods Sixty-five CFS subjects were identified from a r and om-digit-dialing survey of Wichita , Kansas residents and followed for up to 3 years . We evaluated changes in CFS classification ( partial or total remission , alternative medical or psychiatric diagnoses ) , CFS case-defining criteria , wellness scores , hours of activities and sleep , and treatments used to reduce fatigue . Associations between risk factors and outcomes were determined by use of logistic regression and generalized estimating equations models . Results Only 20%-33 % of the subjects were classified as having CFS at follow-up , 56.9 % ever experienced partial or total remission , 10 % sustained total remission , and 23.1 % received alternative diagnoses , of which 20 % were sleep disorders . Higher fatigue severity scores and total number of symptoms were negatively associated with ever remitting . Duration of illness ≤ 2 years was positively associated with sustained remission . Unrefreshing sleep persisted in at least 79 % of the subjects across all periods but , as with most of the CFS symptoms , tended to be less frequent over time . The number of activities affected by fatigue decreased over time , while wellness scores increased . At any follow-up , more than 35 % of subjects reporting reduced fatigue used complementary and alternative medicine therapies , and of those subjects , at least 50 % thought these therapies were responsible for reducing their fatigue . Conclusions The clinical course of CFS was characterized by an intermittent pattern of relapse and remission . Remission rates documented by our population -based study were similar to those reported in clinical studies . Shorter illness duration was a significant predictor of sustained remission , and thus early detection of CFS is of utmost importance . The persistence of sleep complaints and identification of sleep disorders suggest that CFS subjects be evaluated for sleep disturbances , which could be treated AIM To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome ( IBS ) and significant bloating . METHODS Forty-eight patients with Rome II IBS were r and omized in a parallel group , double-blind design to placebo or VSL # 3 twice daily ( 31 patients received 4 weeks and 17 patients 8 weeks of treatment ) . Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal . Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment . Weekly satisfactory relief of abdominal bloating was assessed . RESULTS Treatment with VSL # 3 was associated with reduced flatulence over the entire treatment period ( placebo 39.5 + /- 2.6 vs VSL # 3 29.7 + /- 2.6 , P = 0.011 ) ; similarly , during the first 4 weeks of treatment , flatulence scores were reduced ( placebo 40.1 + /- 2.5 vs VSL # 3 30.8 + /- 2.5 , P = 0.014 ) . Proportions of responders for satisfactory relief of bloating , stool-related symptoms , abdominal pain and bloating scores were not different . Colonic transit was retarded with VSL # 3 relative to placebo ( colon geometric center 2.27 + /- 0.20 vs 2.83 + /- 0.19 , P = 0.05 respectively ) . CONCLUSION VSL # 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating Human intestinal microbiota plays an important role in the maintenance of host health by providing energy , nutrients , and immunological protection . Intestinal dysfunction is a frequent complaint in myalgic encephalomyelitis/chronic fatigue syndrome ( ME/CFS ) patients , and previous reports suggest that dysbiosis , i.e. the overgrowth of abnormal population s of bacteria in the gut , is linked to the pathogenesis of the disease . We used high-throughput 16S rRNA gene sequencing to investigate the presence of specific alterations in the gut microbiota of ME/CFS patients from Belgium and Norway . 43 ME/CFS patients and 36 healthy controls were included in the study . Bacterial DNA was extracted from stool sample s , PCR amplification was performed on 16S rRNA gene regions , and PCR amplicons were sequenced using Roche FLX 454 sequencer . The composition of the gut microbiota was found to differ between Belgian controls and Norwegian controls : Norwegians showed higher percentages of specific Firmicutes population s ( Roseburia , Holdemania ) and lower proportions of most Bacteroidetes genera . A highly significant separation could be achieved between Norwegian controls and Norwegian patients : patients presented increased proportions of Lactonifactor and Alistipes , as well as a decrease in several Firmicutes population s. In Belgian subjects the patient/control separation was less pronounced , however some abnormalities observed in Norwegian patients were also found in Belgian patients . These results show that intestinal microbiota is altered in ME/CFS . High-throughput sequencing is a useful tool to diagnose dysbiosis in patients and could help design ing treatments based on gut microbiota modulation ( antibiotics , pre and probiotics supplementation ) Purpose The aim of this study is to test in a double-blinded , r and omised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms , colonic transit and quality of life in irritable bowel syndrome ( IBS ) patients who meet Rome III criteria . Background There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS . Methods This is a double-blinded , r and omised placebo-controlled study of a symbiotic mixture ( Probinul , 5 g bid ) over 4 weeks after 2 weeks of run-in . The primary endpoints were global satisfactory relief of abdominal flatulence and bloating . Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief . The secondary endpoints were change in abdominal bloating , flatulence , pain and urgency by a 100-mm visual analog scale , stool frequency and bowel functions on vali date d adjectival scales ( Bristol Scale and sense of incomplete evacuation ) . Pre- and post-treatment colonic transit time ( Metcalf ) and quality of life ( SF-36 ) were assessed . Results Sixty-four IBS patients ( symbiotic n = 32 , 64 % females , mean age 38.7 ± 12.6 years ) were studied . This symbiotic mixture reduced flatulence over a 4-week period of treatment ( repeated- measures analysis of covariance , p < 0.05 ) . Proportions of responders were not significantly different between groups . At the end of the treatment , a longer rectosigmoid transit time and a significant improvement in most SF-36 scores were observed in the symbiotic group . Conclusions This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients , a lack of adverse events and a good side-effect profile ; however , it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating . Further studies are warranted Background Recent data suggest a role for the intestinal microbiota in the pathogenesis of functional bowel disorders ( FBDs ) . Probiotic studies in FBDs generated inconsistent results suggesting a strain-specific and product-specific effect . Aim To investigate the clinical efficacy of Lactobacillus acidophilus NCFM ( L-NCFM ) and Bifidobacterium lactis Bi-07 ( B-LBi07 ) in nonconstipation FBDs . Methods A double-blind , placebo-control clinical trial of the probiotic bacterias L-NCFM and B-LBi07 twice a day ( 2 × 1011CFU/d ) versus placebo over 8 weeks . Primary endpoints were global relief of gastrointestinal symptoms and satisfaction with treatment . Secondary endpoints were change in symptoms severity , well-being , and quality of life . Microbiological effect was assessed by quantitative real time polymerase chain reaction on fecal sample s. Results Sixty patients ( probiotic , n=31 ; placebo , n=29 ) , 72 % females , 84 % whites , mean age 37 years . Abdominal bloating improved in the probiotics compared with the placebo group at 4 weeks ( 4.10 vs 6.17 , P=0.009 ; change in bloating severity P=0.02 ) and 8 weeks ( 4.26 vs 5.84 , P=0.06 ; change in bloating severity P<0.01 ) . Analyses on the irritable bowel syndrome subgroup ( n=33 ) showed similar results . Conclusions L-NCFM and B-LBi07 twice a day improve symptoms of bloating in patients with FBDs . These data supports the role of intestinal bacteria in the pathophysiology of FBD and the role for probiotic bacteria in the management of these disorders Certain therapeutic microbes , including Bifidobacteria infantis ( B. infantis ) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions ; however , the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear . In this study , we assessed the impact of oral administration of B. infantis 35624 , for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis ( UC ) ( n = 22 ) , chronic fatigue syndrome ( CFS ) ( n = 48 ) and psoriasis ( n = 26 ) in three separate r and omized , double-blind , placebo-controlled interventions . Additionally , the effect of B. infantis 35624 on immunological biomarkers in healthy subjects ( n = 22 ) was assessed . At baseline , both gastrointestinal ( UC ) and non-gastrointestinal ( CFS and psoriasis ) patients had significantly increased plasma levels of C-reactive protein ( CRP ) and the pro-inflammatory cytokines tumor necrosis factor α ( TNF-α ) and interleukin-6 ( IL-6 ) compared with healthy volunteers . B. infantis 35624 feeding result ed in reduced plasma CRP levels in all three inflammatory disorders compared with placebo . Interestingly , plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS . Furthermore , in healthy subjects , LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells ( P BMC s ) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding . These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions . In conclusion , these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system BACKGROUND Therapy trials with bacterial compounds in irritable bowel syndrome ( IBS ) have produced conflicting results and , so far , an E.-coli preparation has not been used . METHODS Two hundred and ninety-eight patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound Symbioflor-2 ( Symbiopharm GmbH , Herborn , Germany ) , an Escherichia coli product ( N = 148 ) , or placebo ( n = 150 ) in a double-blinded , r and omized fashion . Patients were seen weekly by the physician , who assessed the presence of core IBS symptoms . Both an abdominal pain score ( APS ) as well as a general symptom score ( GSS ) were used as primary endpoints . Responders had to have complete absence of IBS core symptoms at > or = 1 visit during treatment . RESULTS The responder rate in GSS to the drug was 27 / 148 ( 18.2 % ) in comparison to placebo with 7 / 150 ( 4.67 % ) ( p = 0.000397 ) . The improvement in APS was 28 / 148 ( 18.9 % ) and 10 / 150 ( 6.67 % ) for placebo ( p = 0.001649 ) . The response was reached from visit 3 onwards with both medication and placebo . Post-hoc analysis revealed no significant differences in efficacy of the drug between the gender and different age groups . CONCLUSION Treatment of IBS with the probiotic Symbioflor-2 is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners and by gastroenterologists Background and Aim . The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated . Methods . A r and omized , double-blind , three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups ( F_1 , F_2 , and F_3 ) . Each group received a daily oral administration of probiotic mixtures ( for 60 days ) F_1 or F_2 or placebo F_3 , respectively . Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics . Results . The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period ( t60 ) and was maintained quite similar during the follow-up period ( t90 ) . Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3 , and the same level was maintained during the follow-up period . Conclusions . Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota . This clinical study is registered with the clinical study registration number IS RCT N15032219 BACKGROUND Most previous estimates of the prevalence of chronic fatigue syndrome ( CFS ) have derived largely from treated population s , and have been biased by differential access to health care treatment linked with sex , ethnic identification , and socioeconomic status . OBJECTIVE To assess the point prevalence of CFS in an ethnically diverse r and om community sample . DESIGN AND PARTICIPANTS A sample of 28,673 adults in Chicago , Ill , was screened by telephone , and those with CFS-like symptoms were medically evaluated . MAIN OUTCOME MEASURES AND ANALYSES : Self-report question naires , psychiatric evaluations , and complete medical examinations with laboratory testing were used to diagnose patients with CFS . Univariate and multivariate statistical techniques were used to delineate the overall rate of CFS in this population , and its relative prevalence was subcategorized by sex , ethnic identification , age , and socioeconomic status . RESULTS There was a 65.1 % completion rate for the telephone interviews during the first phase of the study . Findings indicated that CFS occurs in about 0.42 % ( 95 % confidence interval , 0.29%-0.56 % ) of this r and om community-based sample . The highest levels of CFS were consistently found among women , minority groups , and persons with lower levels of education and occupational status . CONCLUSIONS Chronic fatigue syndrome is a common chronic health condition , especially for women , occurring across ethnic groups . Earlier findings suggesting that CFS is a syndrome primarily affecting white , middle-class patients were not supported by our findings Abstract Objective . Meta-analyses have indicated effect of probiotics on irritable bowel syndrome ( IBS ) . However , few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting . We aim ed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up . Material and methods . We r and omized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 1010 CFU per capsule . Primary endpoint was proportion of responders defined as patients reporting adequate relief ( AR ) at least 50 % of the time in the 6-month treatment period . Secondary outcomes were proportions of patients reporting AR at different time points , and change in gastrointestinal symptoms and health-related quality of life ( HrQOL ) from baseline to 6 and 12 months . Results . A total of 131 patients were included in this study . The proportion of responders in the treatment period was 52 % ( 35/67 ) in the probiotic group versus 41 % ( 26/64 ) in the placebo group , p = 0.18 . Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment . Patients improved in HrQOL , but with no statistically significant difference between the groups . Conclusion . During a 6-month treatment period , we were not able to detect a positive effect of probiotic when compared with placebo BACKGROUND Chronic fatigue syndrome ( CFS ) is a disorder of unknown etiology , consisting of prolonged , debilitating fatigue , and a multitude of symptoms including neurocognitive dysfunction , flu-like symptoms , myalgia , weakness , arthralgia , low- grade fever , sore throat , headache , sleep disturbances , and swelling and tenderness of lymph nodes . No effective treatment for CFS is known . OBJECTIVE The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide ( NADH ) i.e. , ENADA the stabilized oral absorbable form , in a r and omized , double-blind , placebo-controlled crossover study in patients with CFS . Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects . METHODS Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study . Medical history , physical examination , laboratory studies , and question naire were obtained at baseline , 4 , 8 , and 12 weeks . Subjects were r and omly assigned to receive either 10 mg of NADH or placebo for a 4-week period . Following a 4-week washout period , subjects were crossed to the alternate regimen for a final 4-week period . RESULTS No severe adverse effects were observed related to the study drug . Within this cohort of 26 patients , 8 of 26 ( 31 % ) responded favorably to NADH in contrast to 2 of 26 ( 8 % ) to placebo . Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients . CONCLUSION Collectively , the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinical ly perplexing disorder Objectives Efficacy of symbiotics in patients with irritable bowel syndrome ( IBS ) remains unknown . Methods Patients were r and omized to a prebiotic ( n=135 ) , or a symbiotic formulation containing Lactobacillus paracasei B21060 ( Flortec , n=132 ) . Primary efficacy was the responder rate for pain and global relief of symptoms in the overall population and in patients with predominant diarrhea ( n=47 ) . Post hoc time-trend analyses for changes within each treatment were carried out . Results Patients with absent/mild pain amounted to 54.7 % in the symbiotic group and to 57.4 % in the prebiotic group at treatment week 4 , and to 53.9 % and 53.4 % at the end of treatment . Patients with amelioration of well-being were , respectively , 60.7 % versus 61.7 % at treatment week 4 , and 63.3 % versus 60.9 % at the end of treatment . Within each treatment group , patients with absent/mild pain increased in the Flortec and the prebiotic group , but time trend analyses were significant only for Flortec ( P=0.019 ) . In IBS-predominant diarrhea , Flortec significantly reduced bowel movements , pain , and IBS scores . Conclusions To improve pain and well-being , Flortec is encouraging in patients with diarrhea predominant IBS . To establish its efficacy for the majority of IBS patients , Flortec has to be compared with an inert placebo in future work Background Some probiotics have shown efficacy for patients with irritable bowel syndrome ( IBS ) . Lactobacillus ( L. ) plantarum MF1298 was found to have the best in vitro probiotic properties of 22 strains of lactobacilli . The aim of this study was to investigate the symptomatic effect of L. plantarum MF1298 in subjects with IBS . Primary outcome was treatment preference and secondary outcomes were number of weeks with satisfactory relief of symptoms and IBS sum score . Methods The design was a r and omised double blind placebo-controlled crossover trial . 16 subjects with IBS underwent two three-week periods of daily intake of one capsule of 1010 CFU L. plantarum MF 1298 or placebo separated by a four-week washout period . Results Thirteen participants ( 81 % ; 95 % CI 57 % to 93 % ; P = 0.012 ) preferred placebo to L. plantarum MF1298 treatment . The mean ( SD ) number of weeks with satisfactory relief of symptoms in the periods with L. plantarum MF1298 and placebo were 0.50 ( 0.89 ) and 1.44 ( 1.26 ) , respectively ( P = 0.006 ) . IBS sum score was 6.44 ( 1.81 ) in the period with L. plantarum MF1298 treatment compared with 5.35 ( 1.77 ) in the period with placebo ( P = 0.010 ) . With a clinical ly significant difference in the IBS sum score of 2 in disfavour of active treatment , the number needed to harm was 3.7 , 95 % CI 2.3 to 10.9 . Conclusions This trial shows for the first time an unfavourable effect on symptoms in subjects with IBS after intake of a potential probiotic . The trial registration number Clinical trials NCT00355810 BACKGROUND Proton pump inhibitors may foster intestinal dysbiosis and related bowel symptoms . AIM To evaluate the effect of Lactobacillus paracasei F19 on bowel symptom onset in patients on long-term proton pump inhibitors . METHODS In this r and omized , double-blind , placebo-controlled study , patients with typical gastroesophageal reflux disease symptoms receiving pantoprazole 40 mg/d for six months were r and omly assigned to receive : ( A ) Lactobacillus paracasei F19 bid for three days/week for six months ; ( B ) placebo bid for three days/week for six months ; ( C ) Lactobacillus paracasei F19 bid for three days/week for three months and placebo bid for three days/week for the following three months ; ( D ) placebo bid for three days/week for three months and Lactobacillus paracasei F19 bid for three days/week for the following three months . Bloating , flatulence , abdominal pain and bowel habit were assessed monthly . RESULTS 100/312 patients were enrolled . In the parallel groups , the treatment-by-time interaction affected bloating ( p = 0.015 ) , while Lactobacillus paracasei F19 treatment alone affected flatulence ( p = 0.011 ) . Moreover , the treatment-by-time interaction significantly affected the mean score of bloating ( p = 0.01 ) and flatulence ( p < 0.0001 ) , the mean stool form ( p = 0.03 ) and mean stool frequency/week ( p = 0.016 ) . Analysis of the cross-over groups , limited to the first three months because of carry-over effect , confirmed these results . CONCLUSION Lactobacillus paracasei F19 supplementation prevents bowel symptom onset in patients on long-term proton pump inhibitors Purpose To study the therapeutic effects of probiotic Escherichia coli Nissle 1917 ( EcN ) in irritable bowel syndrome ( IBS ) and identify subgroups benefiting most . Background Some trials investigating therapeutic effects in irritable bowel syndrome have shown benefits in IBS subgroups only . Probiotic treatment seems to be promising . Methods Patients with irritable bowel syndrome ( 120 ; Rome II ) were recruited to a prospect i ve double-blind study and r and omized to either EcN ( n = 60 ) or placebo ( n = 60 ) given for 12 weeks . Objectives were to describe efficacy and safety of EcN in different groups of irritable bowel syndrome . Outcome was assessed by ‘ Integrative Medicine Patient Satisfaction Scale ’ . Results Altogether , the responder rate was higher in the EcN than in the placebo group . However , only after 10 and 11 weeks , the differences were significant ( Δ 20.0 % points [ 95 % CI 2.6 ; 37.4 ] , p = 0.01 and Δ 18.3 % points [ 95 % CI 1.0 ; 35.7 ] , p = 0.02 , respectively ) . The best response was observed in the subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel syndrome onset ( Δ 45.7 % points , p = 0.029 ) . No significant differences were observed in any other subgroup . Both treatment groups showed similar adverse events and tolerance . Conclusions Probiotic EcN shows effects in irritable bowel syndrome , especially in patients with altered enteric microflora , e.g. after gastroenterocolitis or administration of antibiotics Aim : To investigate the effects of a probiotic formulation , VSL#3 , on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea Background : The clinical effect of probiotics on irritable bowel syndrome ( IBS ) is still controversial . Aims : We aim ed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS ( D-IBS ) . Methods : Fifty patients with D-IBS were r and omized into placebo or probiotic mixture ( Lactobacillus acidophilus , Lactobacillus plantarum , Lactobacillus rhamnosus , Bifidobacterium breve , Bifidobacterium lactis , Bifidobacterium longum , and Streptococcus thermophilus 1.0 × 1010 CFU ) groups . Treatment was taken daily for 8 weeks . The primary outcome was adequate relief ( AR ) of overall IBS symptoms , which was assessed weekly for 10 weeks . A responder was defined as a patient who experienced AR for at least half of the 10-week study period . Secondary outcomes included the effects on individual symptoms , stool parameters , and IBS quality of life . The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis ( DGGE ) . Results : The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period ( P<0.05 ) . The proportion of responders was significantly higher in the probiotics group than in the placebo group ( 48 % vs. 12 % , P=0.01 ) . Stool consistency improved significantly in the probiotics group compared with the placebo group . Percent changes in individual symptom scores were similar in the 2 groups , but IBS quality of life improvement tended to be higher in the probiotics group . Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group ( 69.5 % vs. 56.5 % , P=0.005 ) . Conclusions : The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients , although it had no significant effect on individual symptoms . The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota BACKGROUND Probiotics may help resolve bowel symptoms and improve quality of life . We investigated the effects of 12 weeks of probiotics administration in colorectal cancer patients . METHODS We conducted a double-blind , r and omized , placebo-controlled trial . The participants took probiotics ( Lacidofil ) or placebo twice a day for 12 weeks . The cancer-related quality of life ( FACT ) , patient 's health-9 ( PHQ-9 ) , and bowel symptom question naires were completed by each participant . RESULTS We obtained data for 32 participants in the placebo group and 28 participants in the probiotics group . The mean ages of total participants were 56.18 ± .86 years and 58.3 % were male . Administration of probiotics significantly decreased the proportion of patients suffering from irritable bowel symptoms ( 0 week vs. 12 week ; 67.9 % vs. 45.7 % , p=0.03 ) , improved colorectal cancer-related FACT ( baseline vs. 12 weeks : 19.79 ± 4.66 vs. 21.18 ± 3.67 , p=0.04 ) and fatigue-related FACT ( baseline vs. 12 weeks : 43.00 ( 36.50 - 45.50 ) vs. 44.50 ( 38.50 - 49.00 ) , p=0.02 ) and PHQ-9 scores ( 0 weeks vs. 12 weeks ; 3.00 ( 0 - 8.00 ) vs. 1.00 ( 0 - 3.00 ) , p=0.01 ) . We found significant differences in changes of the proportion of patients with bowel symptoms ( p<0.05 ) , functional well-being scores ( p=0.04 ) and cancer-related FACT scores ( p=0.04 ) between the two groups . CONCLUSION Probiotics improved bowel symptoms and quality of life in colorectal cancer survivors Introduction This preliminary study aim ed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome ( IBS-D ) . The other objectives were to document any clinical improvement as judged by symptoms , quality of life , and histology . Patients and methods This was a r and omized , double blind , placebo-controlled trial in which S. boulardii , 750 mg/day , or placebo was administered for 6 weeks in IBS-D patients , in addition to ispaghula husk st and ard treatment . Results Thirty-seven patients received S. boulardii and 35 patients received the placebo . As compared with placebo , the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 ( IL-8 ) and tumor necrosis factor-&agr ; ( P<0.001 ) and an increase in anti-inflammatory IL-10 levels , as well as an increase in the tissue IL-10/IL-12 ratio ( P<0.001 ) . No significant change in the blood and tissue levels of cytokines was found in the placebo group . Bowel-related IBS-D symptoms reported in the patients ’ daily diary improved in both groups . However , overall improvement in the quality of life was more marked in the S. boulardii group . Although baseline histological findings were mild , an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates ( P=0.017 and 0.018 ) , epithelial mitosis ( P=0.003 ) , and intraepithelial lymphocytes ( P=0.024 ) . No serious adverse events were found in either group . Conclusion S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile , histology , and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial AIM to evaluate potential improvement effect for probiotic E. coliNissle 1917 in the management of refractory IBS in an Iranian population . METHODS a double blind placebo controlled approach has been used in the current clinical trial . 139 confirmed IBS patients were included into the study , and were given probiotic E.coli Nissle 1917 for 6 weeks . 11 items Birmingham IBS Symptom Question nairehas been used for evaluation of changes in the symptoms every 2 weeks . RESULTS sixty eight subjects ( 49 % ) were males . Mean±SD age of the participants was 38±13.3 years . 49(35.3 % ) of the patients were diarrhea-predominant . The total scores showed no significant difference between the intervention vs. control group(-6.7±6.8 vs. -6.7±6.5 , respectively ; p=0.95 ) ; neither did any of the question naire items any significant alterations in the two groups . After stratification of patients based on their IBS type , diarrhea-predominant patients showed a positive response to the probiotic improving their sleep ( p=0.05 and 0.03 at weeks 2 and 6 , respectively ) . Patients with constipation-predominant IBS showed no response to the probiotic ; while patients with diarrhea-constipation mixed IBS showed unfavorable response to the probiotic in the need for strain to pass a motion compared to the placebo ( p=0.03 and 0.02 at weeks 4 and 6 , respectively ) . CONCLUSION probiotic therapy with E.coli Nissle 1917 was not able to induce significant improvement in the symptoms of patients with non-categorized IBS . Nevertheless , when IBS patients were recategorized to subgroups according to their main symptoms , evaluation of the efficacy of the probiotic on some individual items in the symptom list reached the significance level . Prospect i ve clinical trials are recommended to confirm our findings AIM To assess the symptomatic efficacy of Lactobacillus plantarum 299v ( L. plantarum 299v ) ( DSM 9843 ) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome ( IBS ) patients fulfilling the Rome III criteria . METHODS In this double blind , placebo-controlled , parallel- design ed study , subjects were r and omized to daily receive either one capsule of L. plantarum 299v ( DSM 9843 ) or placebo for 4 wk . Frequency and intensity of abdominal pain , bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated . RESULTS Two hundred and fourteen IBS patients were recruited . After 4 wk , both pain severity ( 0.68 + 0.53 vs 0.92 + 0.57 , P < 0.05 ) and daily frequency ( 1.01 + 0.77 vs 1.71 + 0.93 , P < 0.05 ) were lower with L. plantarum 299v ( DSM 9843 ) than with placebo . Similar results were obtained for bloating . At week 4 , 78.1 % of the patients scored the L. plantarum 299v ( DSM 9843 ) symptomatic effect as excellent or good vs only 8.1 % for placebo ( P < 0.01 ) . CONCLUSION A 4-wk treatment with L. plantarum 299v ( DSM 9843 ) provided effective symptom relief , particularly of abdominal pain and bloating , in IBS patients fulfilling the Rome III criteria Background : Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology . The effect of probiotics in this syndrome remains unclear BACKGROUND We aim ed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a r and omized double-blind placebo-controlled clinical trial . METHODS Overall , 179 adults with irritable bowel syndrome ( Rome III criteria ) were r and omized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86 , F : 84 % , age : 42.5 ± 12.5 ) , or placebo ( n = 93 , F : 88 % , age : 45.4 ± 14 ) for 8 weeks followed by a 3-week washout period . After a 2-week run-in period , cardinal symptoms ( abdominal pain/discomfort , bloating/distension , bowel movement difficulty ) and changes in stool frequency and consistency were recorded daily and assessed each week . A safety assessment was carried out throughout the study . RESULTS The proportion of responders , defined by an improvement of abdominal pain/discomfort , was significantly higher ( p = 0.04 ) in the treated group than the placebo group ( 63 % vs 47 % , OR = 1.88 , 95 % , CI : 0.99 - 3.57 ) in the last 4 weeks of treatment . A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms . Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency . CONCLUSION Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification . Thus , Saccharomyces cerevisiae may be a new promising c and i date for improving abdominal pain in subjects with irritable bowel syndrome Background Irritable bowel syndrome ( IBS ) is a widespread functional disorder of the digestive tract . Its aetiology is unknown and therapeutic options are limited . Recent reports suggest that probiotics may have a role in regulating the motility of the digestive tract . Aim To assess the efficacy of Lactobacillus plantarum 299V ( LP299V ) in patients with IBS . Patients and methods Forty patients were r and omized to receive either LP299V in liquid suspension ( 20 patients ) or placebo ( 20 patients ) over a period of 4 weeks . Clinical examination was performed at baseline and at the end of the study . Additionally , patients assessed their symptoms by applying a scoring system . Results All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group ( P = 0.0012 ) . There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo ( P = 0.17 ) . With regards to all IBS symptoms an improvement was noted in 95 % of patients in the LP299V group vs 15 % of patients in the placebo group ( P < 0.0001 ) . Conclusions LP299V seems to have a beneficial effect in patients with IBS . Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS Therapy trials with bacterial compounds in irritable bowel syndrome ( IBS ) have produced conflicting results . This study was performed in 1988 and 1989 , and was re-analysed according to current IBS st and ards . Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor((R ) ) ( Symbiopharm GmbH , Herborn , Germany ) , an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli , or placebo in a double-blinded , r and omized fashion . Patients were seen weekly by the physician , who assessed the presence of core IBS symptoms . Responders had at least a 50 % decrease in global symptom score ( GSS ) and in abdominal pain score ( APS ) reports at > /=1 visit during treatment . The responder rate in GSS to the drug was 102/149 ( 68.5 % ) in comparison to placebo with 56/148 ( 37.8 % ) ( P < 0.001 ) , the improvement in APS was 108/149 ( 72.5 % ) and 66/148 ( 44.6 % ) respectively ( P = 0.001 ) . The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report . Kaplan-Meier analysis revealed a mean response time of 4 - 5 weeks for active treatment and more than 8 weeks for placebo ( P < 0.0001 ) . Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners |
11,218 | 29,419,895 | Last , review authors found no comparable data for the secondary outcome inflammatory markers .
The effects of pulmonary artery perfusion with blood during cardiopulmonary bypass ( CPB ) are uncertain owing to the small numbers of participants included in meta-analyses .
Risks of death and serious adverse events may be higher with pulmonary artery perfusion with blood during CPB , and robust evidence for any beneficial effects is lacking . | BACKGROUND Available evidence has been inconclusive on whether pulmonary artery perfusion during cardiopulmonary bypass ( CPB ) is associated with decreased or increased mortality , pulmonary events , and serious adverse events ( SAEs ) after open heart surgery .
To our knowledge , no previous systematic review s have included meta-analyses of these interventions .
OBJECTIVES To assess the benefits and harms of single-shot or continuous pulmonary artery perfusion with blood ( oxygenated or deoxygenated ) or a preservation solution compared with no perfusion during cardiopulmonary bypass ( CPB ) in terms of mortality , pulmonary events , serious adverse events ( SAEs ) , and increased inflammatory markers for adult surgical patients . | Introduction Absence of pulmonary perfusion during cardiopulmonary bypass ( CPB ) may be associated with reduced postoperative oxygenation . Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease ( COPD ) undergoing cardiac surgery . Methods 90 patients were r and omised to receive pulmonary artery perfusion during CPB with either oxygenated blood ( n=30 ) or histidine-tryptophan-ketoglutarate ( HTK ) solution ( n=29 ) compared with no pulmonary perfusion ( n=31 ) . The co primary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model ( MEM ) . Secondary outcomes were tracheal intubation time , serious adverse events , mortality , days alive outside the intensive care unit ( ICU ) and outside the hospital . Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion ( mean difference ( MD ) 0.94 ; 95 % CI 0.05 to 1.83 ; p=0.04 ) . The blood group had also a higher oxygenation index both longitudinally ( MEM , p=0.009 ) and at 21 hours ( MD 0.99 ; CI 0.29 to 1.69 ; p=0.007 ) compared with the HTK group . The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32 . Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion ( MEM , p=0.57 and 0.17 ) . Similarly , at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion ( MD 0.06 ; 95 % CI −0.73 to 0.86 ; p=0.87 ) . There were no statistical significant differences between the groups for the secondary outcomes . Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery . Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation . Trial registration number NCT01614951 ; Pre- results OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials OBJECTIVE Improved respiratory outcome has been shown after selective pulsatile pulmonary perfusion ( sPPP ) during cardiopulmonary bypass ( CPB ) . No contemporary study has analysed the impact of sPPP on alveolar and systemic inflammatory response in humans . METHODS Sixty-four patients undergoing a coronary artery bypass graft ( CABG ) were r and omized to sPPP or st and ard CPB ( 32 patients each ) . An alveolar-arterial oxygen gradient ( A-aDO(2 ) ) was measured preoperatively ( T0 ) , at ICU arrival ( T1 ) , 3 h postoperatively ( T2 ) and postextubation ( T3 ) . The bronchoalveolar lavage ( BAL ) was collected at T0 , T1 and T2 . White blood cells ( WBCs ) , neutrophils , mononucleates and lymphocytes in BAL infiltrates were compared between the two groups . A cytokine assay for interleukin-1 ( IL-1 ) , IL-8 , tumour necrosis factor alpha ( TNF-α ) , monocyte chemotactic protein-1 ( MCP-1 ) , growth regulated oncogene-alpha ( GRO-α ) and interferon (IFN)-γ was collected from the BAL and peripheral blood at the same time-points . Repeated-measure analysis of variance and non-parametric statistics were used to assess the between-group and during time differences . RESULTS The two groups proved comparable for perioperative variables . A-aDO(2 ) proved better after sPPP ( group-P = 0.0001 ; group time-P < 0.0001 ) . BAL infiltrates after sPPP showed lower WBCs , neutrophils and lymphocytes ( group-P = 0.0001 , group time-P = 0.0001 for all ) together with higher mononucleates ( group-P = 0.0001 , group time-P = 0.0001 ) . Proinflammatory cytokines and chemokine MCP-1 were lower in BAL after sPPP ( group-P = 0.005 , 0.034 , 0.036 and 0.005 , and group time-P = 0.001 , 0.009 , 0.001 and 0.0001 for IL-1 , IL-8 , TNF-α and MCP-1 , respectively ) , whereas the immune modulator IFN-γ significantly augmented after sPPP ( time-P = 0.0001 ) but remained stable after the st and ard CPB ( time-P = 0.101 , group-P = 001 , group time-P = 0.0001 ) . Indeed , serum cytokines were not different in the two groups during the study ( P = NS at single time-points and as a function of time ) . CONCLUSIONS sPPP attenuates alveolar inflammation , as demonstrated by the lower neutrophilic/lymphocytic alveolar infiltration , and the secretion of anti-inflammatory rather than proinflammatory mediators OBJECTIVE Acute lung injury still accounts for postoperative mortality after cardiopulmonary bypass ( CPB ) . The safety and the efficacy of pulsatile pulmonary perfusion ( PPP ) during CPB were analyzed . Preliminary results of the first PPP trial in human beings are reported . METHODS Thirty low-risk coronary artery bypass grafting ( CABG ) patients were prospect ively r and omized to receive PPP with oxygenated blood during CPB and aortic cross-clamping ( 15 patients , PPP-group ) or to conventional CPB ( 15 patients , control group ) . Alveolo-arterial oxygen gradient ( A-aDO(2 ) ) was set as the primary end point and collected preoperatively , at intensive care unit ( ICU ) arrival ( T1 ) , 3h postoperatively ( T2 ) , and post extubation ( T3 ) . Secondary end points were collected at the same time points and consisted of respiratory indices ( partial pressure of arterial oxygen/fraction of inspired O(2 ) ( PaO(2)/FiO(2 ) ) , lung compliance , mixed-venous partial pressure of oxygen ( pO(2 ) ) ) and hemodynamic pulmonary parameters ( indexed pulmonary vascular resistances ( PVRI ) , pulmonary arterial pressure ( PAP ) , pulmonary capillary wedge pressure ( PCWP ) , and cardiac index ( CI ) ) . Bronchoalveolar lavage ( BAL ) fluid was collected preoperatively , at ICU arrival ( T1-BAL ) and after 4h . RESULTS There were no PPP-related complications . Patients undergoing PPP showed a better preserved A-aDO(2 ) ( group-p=0.001 ) throughout the study period ( group × time-p = 0.0001 ) . PaO(2)/FiO(2 ) and lung compliance were better preserved by PPP ( group-p and group × time-p ≤ 0.05 for all ) . Pulmonary hemodynamic status was positively influenced by PPP , as shown by the higher CI ( group-p=0.0001 , group × time-p = 0.0001 ) , and the lower PVRI , PAP , and PCWP ( group-p ≤0.001 , group × time-p=0.0001 for all ) . Postoperative BAL specimens demonstrated a lower absolute count of white blood cells ( group-p=0.0001 ) , a higher percentage of monocytes/macrophages ( group-p=0.027 ) , and a lower percentage of neutrophils ( group-p=0.015 ) after PPP . CONCLUSIONS Oxygenated blood PPP proved safe and significantly ameliorated pulmonary hemodynamic parameters and respiratory indices in low-risk CABG OBJECTIVE We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting . The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs . METHODS Eighteen consecutive patients undergoing coronary artery bypass grafting were r and omly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta ( routine circulation , ten patients ) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery ( bilateral circulation , eight patients ) . Blood was simultaneously drawn from right atrium and pulmonary vein at 1 , 10 and 20 min reperfusion . The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined . Because of considerable interindividual scatter , the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point . RESULTS At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were + 44+/-15 % and + 43+/-28 % of the respective right atrial values . The respective values in bilateral circulation were -3+/-4 % and -6+/-7 % ( P=0.02 and P=0.05 vs. respective right atrium ) . Similar increments were found after 10 and 20 min . Platelet-monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation ( -21+/-6 % ) , but washed out in bilateral circulation ( + 5+/-8 % , P=0 . 007 ) . At 20 min reperfusion , activated polymorphonuclear neutrophils ( PMN ) were retained in routine circulation ( -16+/-9 % ) but washed out in bilateral circulation ( + 19+/-29 % , P=0.05 ; all data given as mean+/-SEM ) . CONCLUSIONS Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping This review summarizes the (patho)-physiological effects of ventilation with high FiO2 ( 0.8–1.0 ) , with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies . Hyperoxia is a cornerstone of the acute management of circulatory shock , a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements ( i.e. , the oxygen dept ) is crucial for survival , at least after trauma . On the other h and , “ oxygen toxicity ” due to the increased formation of reactive oxygen species limits its use , because it may cause serious deleterious side effects , especially in conditions of ischemia/reperfusion . While these effects are particularly pronounced during long-term administration , i.e. , beyond 12–24 h , several retrospective studies suggest that even hyperoxemia of shorter duration is also associated with increased mortality and morbidity . In fact , albeit the clinical evidence from prospect i ve studies is surprisingly scarce , a recent meta- analysis suggests that hyperoxia is associated with increased mortality at least in patients after cardiac arrest , stroke , and traumatic brain injury . Most of these data , however , originate from heterogenous , observational studies with inconsistent results , and therefore , there is a need for the results from the large scale , r and omized , controlled clinical trials on the use of hyperoxia , which can be anticipated within the next 2–3 years . Consequently , until then , “ conservative ” O2 therapy , i.e. , targeting an arterial hemoglobin O2 saturation of 88–95 % as suggested by the guidelines of the ARDS Network and the Surviving Sepsis Campaign , represents the treatment of choice to avoid exposure to both hypoxemia and excess hyperoxemia Background Five to thirty percent of patients undergoing cardiac surgery present with chronic obstructive pulmonary disease ( COPD ) and have a 2- to 10-fold higher 30-day mortality risk . Cardiopulmonary bypass ( CPB ) creates a whole body systemic inflammatory response syndrome ( SIRS ) that could impair pulmonary function . Impaired pulmonary function can , however , be attenuated by pulmonary perfusion with oxygenated blood or custodiol HTK ( histidine-tryptophan-ketoglutarate ) solution . Methods / Design The Pulmonary Protection Trial ( PP-Trial ) r and omizes 90 patients undergoing CPB-dependent cardiac surgery to evaluate whether pulmonary perfusion with oxygenated blood or custodiol HTK solution reduces postoperative pulmonary dysfunction in COPD patients . Further , we aim for a non-r and omized evaluation of postoperative pulmonary function after transcatheter aortic-valve implantation ( TAVI ) . The primary outcome measure is the oxygenation index measured from anesthesia induction to the end of surgery and until 24 hours after anesthesia induction for a total of six evaluations . Discussion Patients with COPD may be impaired by hypoxemia and SIRS . Thus , prolonged recovery and even postoperative complications and death may be reflected by the degree of hypoxemia and SIRS . The limited sample size does not aim for confirmatory conclusions on mortality , cardiovascular complications or risk of pneumonia and sepsis , but the PP-Trial is considered an important feasibility trial paving the road for a multicenter confirmatory trial . Trial registration Clinical Trials.gov : NCT01614951 Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . OBJECTIVES Patients undergoing cardiac surgery presenting with chronic obstructive pulmonary disease ( COPD ) have a higher 30-day mortality risk . In these patients , pulmonary dysfunction linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass ( CPB ) , which causes pulmonary hypoperfusion . We hypothesize that selective pulmonary perfusion ( sPP ) of the lungs leads to a reduction of pulmonary inflammation and a better clinical outcome . METHODS Fifty-nine COPD patients ( forced expiratory volume in 1 s/vital capacity < 70 % ) undergoing cardiac surgery procedures ( coronary artery bypass grafting 64 % , valve 14 % ) were block-r and omized to sPP ( venous blood , temperature 2 ° C , 4 l ) or st and ard CPB ( 28/28 ) . The primary end-point of the study was to evaluate the effect of pulmonary perfusion on gas exchange by measuring alveolar-arterial oxygen gradient . The surrogate end-points were inflammatory response , intensive care unit ( ICU ) stay , time on respirator ( TOR ) and major adverse cardiac and cerebrovascular events . A cytokine assay for interleukin-1β , IL-6 , IL-10 , tumour necrosis factor-α ( TNF-α ) and polymorphonuclear elastase was performed with peripheral blood at different time-points [ ( t1 ) pre-CPB , ( t2 ) end of CPB , ( t3 ) 3 h , ( t4 ) 24 h , ( t5 ) 48 h postoperatively ] . Repeated-measure analysis of variance and non-parametric statistics were used to assess the between-group and during time differences . RESULTS The two groups proved comparable for perioperative variables . Serum cytokines were not different in the two groups throughout the study ( P > 0.05 at single time-points ) , but as a function of time , the markers of the inflammatory response increased after CBP ( P < 0.05 pre-CPB to 24 h ) . Clinical end-points were statistically comparable in both groups , but with a trend towards a shorter TOR ( 72 ± 159 h/106 ± 193 h ) and ICU stay ( 3.9 ± 7.2 days/5.5 ± 9.2 days ) in the sPP group despite a slightly longer time on extracorporeal circulation ( 120 vs 158 min ) . CONCLUSIONS These results indicate a non-significant trend that repeated hypothermic lung perfusion with venous blood during CPB may have a protective effect on the lungs . A multicentre study design and larger cohort seem necessary to demonstrate the benefits of sPP more clearly OBJECTIVES To investigate markers of splanchnic perfusion and the extent of endotoxemia during cardiopulmonary bypass ( CPB ) and to compare the effects of dopamine and milrinone on both splanchnic perfusion and endotoxemia . DESIGN Prospect i ve , r and omized , blinded study . SETTING University teaching hospital . PARTICIPANTS Twenty-four patients scheduled for elective coronary artery bypass graft surgery ( CABG ) . INTERVENTIONS Patients were allocated to receive placebo ( eight patients ) , dopamine ( eight patients ) , or milrinone ( eight patients ) during CPB , and at seven times intraoperatively assays were performed of arterial and hepatic venous endotoxin levels , as well as measurements and /or calculations of intramucosal gastric pH ( pHi ) , arterial and hepatic venous lactate-pyruvate ratio ( lac/pyr ) , and hepatic venous oxygen saturation ( S(HV)O2 ) . MEASUREMENTS AND MAIN RESULTS Both splanchnic and systemic endotoxin levels increased significantly , and this was unaffected by either dopamine or milrinone . Gastric pHi did not change , and there were only modest increases in lac/pyr , which remained within the normal range of less than 10 in both splanchnic and systemic blood . In the placebo group , S(HV)O2 decreased at the onset of CPB and also significantly decreased during rewarming and at the end of CPB and surgery . In the dopamine-treated patients , S(HV)O2 was greater compared with placebo and milrinone during both hypothermic and rewarming phases . CONCLUSION Endotoxemia occurs during routine CPB . Neither pHi nor lac/pyr values showed adverse change , but hepatic venous oximetry may be a more sensitive indicator of splanchnic dysoxia in that S(HV)O2 was reduced during rewarming . Whether dopamine or milrinone confer protection against splanchnic ischemia remains uncertain BACKGROUND The aim of this study was to evaluate the protective effect of pulmonary perfusion with hypothermic protective solution on lung function after cardiopulmonary bypass in corrections of Tetralogy of Fallot . METHODS Sixty-four consecutive children with Tetralogy of Fallot were r and omly divided into a control group ( n = 30 ) and a protective group ( n = 34 ) . Hypothermic protective solution was infused to the main pulmonary artery in the protective group . Hemodynamics and lung functions were monitored . Concentrations of malondialdehyde , tumor necrosis factor-alpha , von Willebr and factor , and endothelin in plasma were measured . The interleukin-6 and interleukin-8 levels in bronchoalveolar lavage fluid were also determined . Lung biopsy specimens were obtained after weaning from cardiopulmonary bypass . RESULTS Oxygenation values ( oxygen index and alveolar-arterial O(2 ) gradient ) were better preserved in the protective group than in the control group . The time of mechanical ventilation and length of intensive care unit stay were shorter in the protective group compared with the control group . The tumor necrosis factor-alpha and malondialdehyde levels in plasma increased in both groups after operations , and the rising extents were lower in the protective group than in the control group . The von Willebr and factor and endothelin levels in plasma increased more significantly in the control group than in the protective group . The concentrations of interleukin-6 and interleukin-8 in bronchoalveolar lavage fluid were lower in the protective group than in the control group . The examination of histopathology demonstrated capillary hyperemia and hemorrhage , intra-alveolar edema , leukocytes accumulation , mitochondria swelling and vacuolation , and gas-blood barrier broadening in the control group , whereas there were no significant changes in the protective group . The intercellular adhesion molecule-1 expression on lung vascular endothelial cells was stronger in the control group . CONCLUSIONS Lung perfusion with hypothermic protective solution during cardiopulmonary bypass relieved lung injury in corrections of Tetralogy of Fallot . The inhibition of lung vascular endothelial cell injury may be the major mechanism of relieving cardiopulmonary bypass-induced lung injury OBJECTIVE Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection operated on with deep systemic hypothermia . Interaction between neutrophils and pulmonary endothelium along with ischemic insult and reperfusion are the major determinants of lung injury . The aim of this prospect i ve study was to evaluate the effect of continuous pulmonary perfusion during retro grade cerebral perfusion on lung function . METHODS Twenty-two patients referred for acute type A aortic dissection , who were free from preoperative respiratory dysfunction , were assigned prospect ively and alternately to one of 2 treatment groups . Pulmonary perfusion was performed during retro grade cerebral perfusion in group B ( 11 patients ) , whereas the conventional Ueda technique was applied in group A ( 11 patients ) . Lung function was evaluated on the basis of intubation time , scoring of chest radiographs at 12 hours after cardiopulmonary bypass , and Pao(2)/fraction of inspired oxygen ratio assessed from immediately before the operation to 72 hours after termination of cardiopulmonary bypass . RESULTS Study groups were homogeneous for age , sex , interval between symptom onset and surgical operation , previous aortic surgery , preoperative ejection fraction and pulmonary gas exchange function , extent of aortic repair , and concomitant procedures . Cardiopulmonary bypass time , length of retro grade cerebral perfusion , operation time , need for blood substitutes , and surgical revision for bleeding did not differ between treatment groups . Postoperative Pao(2)/fraction of inspired oxygen ratios were higher in group B than in group A , and the difference remained statistically significant throughout the study period . The incidence of prolonged ventilator support ( > 72 hours ) and the severity of the radiographic pulmonary infiltrate score were lower in the perfused group ( 18.2 % vs 72.7 % [ P = .015 ] and 0.81 + /- 0.75 vs 1.8 + /- 0.78 [ P = .028 ] , respectively ) . CONCLUSIONS Continuous pulmonary perfusion provided a better preservation of lung function in patients operated on with deep systemic hypothermia BACKGROUND Pulmonary artery perfusion during cardiopulmonary bypass ( CPB ) is a novel adjunctive method , which can minimize the lung ischemic-reperfusion injury and inflammatory response . This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension . METHODS Between June 2009 and December 2009 , 24 consecutive infants with congenital heart defects and pulmonary hypertension were r and omly divided into perfused group ( n = 12 ) and control group ( n = 12 ) . Oxygen index , alveolar-arterial O2 gradient , serum levels of malondialchehyche ( MDA ) , interleukin (IL)-6 , -8 , -10 , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , and P-selectin were measured before commencement and serially for 48 hours after termination of bypass . RESULTS Oxygenation values were better preserved in the perfused group than in the control group . The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB , but it was restored faster and earlier in the perfused group . The serum levels of IL-8 , sICAM-1 , and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group , except for sICAM-1 . The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups , but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB . The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels . Moreover , there were no significant differences in postoperative clinical characters , except for the intubated time . CONCLUSION In infants with congenital heart defects , pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response BACKGROUND Lung injury after cardiopulmonary bypass is a serious complication for infants with congenital heart disease and pulmonary hypertension . Excessive neutrophil sequestration in the lung occurring after reestablishment of pulmonary circulation implies that interaction between neutrophils and pulmonary endothelium is the major cause of lung injury . METHODS Thirty infants with either ventricular septal defect or atrioventricular septal defect and with pulmonary hypertension were enrolled in this study . We performed continuous pulmonary perfusion during total cardiopulmonary bypass on 16 patients ( perfused group ) and conventional cardiopulmonary bypass on 14 patients ( control group ) . PaO2/FiO2 and neutrophil counts were assessed from immediately before surgery to 24 hours after termination of cardiopulmonary bypass . RESULTS PaO2/FiO2 was higher in the perfused group than in the control group , and the difference was significant throughout the study period . Neutrophil counts decreased below prebypass values in both groups at 30 minutes after aortic unclamping , and the difference was significant in the control group but was not in the perfused group . Duration of postoperative ventilatory support was significantly less in the perfused group . CONCLUSIONS Our study demonstrates that arrested pulmonary circulation during cardiopulmonary bypass is the major risk factor of lung injury and that continuous pulmonary perfusion is effective in preventing lung injury BACKGROUND The present pilot study was conducted to evaluate the effect of isolated short-term lung perfusion during cardiopulmonary bypass ( CPB ) on inflammatory response and oxygenation . METHODS A total of 24 patients undergoing elective cardiac surgery with routine CPB were prospect ively assigned to three groups . Group I ( n = 7 ) , control subjects receiving neither lung perfusion nor ultrafiltration ; group II ( n = 9 ) , patients undergoing lung perfusion ; and group III ( n = 8) , patients undergoing lung perfusion plus ultrafiltration . Lung perfusion consisted of single-shot hypothermic pulmonary artery perfusion with oxygenated blood . Proteins indicative of leukocyte activation and lung injury were measured in plasma and bronchoalveolar lavage fluid ( BALF ) . The alveolar-arterial oxygen gradient ( A-aDO2 ) and the oxygenation index ( PO2/FiO2 ) were also determined . RESULTS Oxygenation values were best preserved in group III , followed by group II . After CPB , elastase-alpha1-proteinase inhibitor complex had increased in plasma in all groups ; in BALF it increased in groups I and II , but not in group III . Alpha2-macroglobulin increased significantly in BALF in group I but not in groups II and III . CONCLUSIONS These preliminary results provide some evidence that single-shot hypothermic lung perfusion with oxygenated blood at the beginning of CPB may have a protective effect on the lungs , especially when combined with ultrafiltration Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
11,219 | 19,018,261 | Sensitivity analyses showed these results to be robust , demonstrating that fulvestrant is an economically viable additional endocrine option in the United Kingdom for the treatment of hormone responsive advanced breast cancer | Drug therapies for advanced breast cancer in hormone-receptor-positive disease include both hormonal and chemotherapies .
Current UK practice is to minimise toxicity by using sequential hormonal agents for as long as clinical ly appropriate .
A Markov model was developed to investigate the cost effectiveness of different sequences of therapies , particularly exploring the effects of adding an additional hormonal agent , fulvestrant , to the treatment pathway . | Estrogens administered in high doses were commonly used for therapy of advanced breast cancer before the introduction of contemporary endocrine therapy . While the mechanism of the antitumor effect is unknown , in vitro investigations have shown estrogens in high concentrations to be toxic to cell growth . Further , it has been shown that exposure of MCF-7 cells to estrogens in low concentrations may enhance the sensitivity and also lower the toxicity threshold to estrogens . This study was design ed to evaluate treatment with diethylstilbestrol ( DES ) in postmenopausal women with advanced breast cancer becoming resistant to estrogen deprivation . Thirty-two patients with advanced breast cancer previously exposed to multiple endocrine treatment regimens ( median 4 , range 2–10 ) were enrolled . Their tumor should have revealed evidence of endocrine sensitivity ( previous partial response or at least stable disease for ≥6 months to therapy ) . Each patient received DES 5 mg t.i.d . Four patients terminated therapy after ≤2 weeks on therapy due to side effects ; another two patients terminated therapy before progression for similar reasons ( one patient after SD for 15 weeks and one with a PR after 39 weeks ) . Four patients obtained CR and six patients PR . In addition , two patients had SD for ≥6 months duration . Five patients had an objective response and one patient a SD lasting for ≥1 year . Our results reveal estrogens administered in high doses may have antitumor effects in breast cancer patients heavily pretreated with endocrine therapy . Such treatment represents a valuable alternative to chemotherapy in selected patients It was previously shown that letrozole ( Femara ) was significantly more potent than anastrozole ( Arimidex ) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer . The objective of this study was to compare letrozole ( 2.5 mg per day ) and anastrozole ( 1 mg per day ) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen . This r and omised , multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients . Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy . Patients had tumours that were either positive for oestrogen and /or progesterone receptors ( 48 % ) or of unknown receptor status ( 52 % ) . The primary efficacy endpoint was time to progression ( TTP ) . Secondary endpoints included objective response , duration of response , rate and duration of overall clinical benefit ( responses and long-term stable disease ) , time to treatment failure , and overall survival , as well as general safety . There was no difference between the treatment arms in TTP ; median times were the same for both treatments . Letrozole was significantly superior to anastrozole in the overall response rate ( ORR ) ( 19.1 % versus 12.3 % , P=0.013 ) , including in predefined subgroups ( receptor status-unknown , and soft-tissue- and viscera-dominant site of disease ) . There were no significant differences between the treatment arms in the rate of clinical benefit , median duration of response , duration of clinical benefit , time to treatment failure or overall survival . Both agents were well tolerated and there were no significant differences in safety . These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy Abstract Purpose . This retrospective evaluation of data from two r and omized , multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy , usually tamoxifen , and on the estrogen receptor ( ER ) antagonist fulvestrant ( ' Faslodex ' ) . Patients and methods . A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection . After progression on fulvestrant , some patients received another endocrine therapy . Responses to subsequent endocrine therapy were assessed using a question naire sent to the trial investigators . Best responses were classified as a complete or partial response ( CR or PR ) , stable disease ( SD ) lasting ≥24 weeks , or disease progression . Results . Follow-up data were available for 54 patients who derived clinical benefit ( CB , defined as CR , PR or SD ) from fulvestrant and who received subsequent endocrine therapy , result ing in a PR in 4 patients , SD in 21 patients , and disease progression in 29 patients . Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy , result ing in a PR in 1 patient , SD in 17 patients , and disease progression in 33 patients . Aromatase inhibitors were used as subsequent endocrine therapy in > 80 % of patients . Conclusions . After progression on fulvestrant , patients may retain sensitivity to other endocrine agents . Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women , and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required Fulvestrant ( ICI 182,780 ) is a new type of estrogen receptor ( ER ) antagonist that down‐regulates the ER and has no known agonist effects . The authors report the prospect ively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly ( n = 428 ) and anastrozole 1 mg daily ( n = 423 ) in postmenopausal women with advanced breast carcinoma ( ABC ) who previously had progressed after receiving endocrine treatment PURPOSE To compare two doses of letrozole ( 0.5 mg and 2.5 mg every day ) and megestrol acetate ( 40 mg qid ) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens . PATIENTS AND METHODS This double-blind , r and omized , multicenter , multinational study enrolled 602 patients , all of whom were included in the primary analysis in the protocol . Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy , had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months , or had experienced disease progression while receiving antiestrogen therapy for advanced disease . Tumors were required to be estrogen receptor- and /or progesterone receptor-positive or of unknown status . Confirmed objective response rate was the primary efficacy variable . Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality -of-life assessment s were collected for 1 year . RESULTS There were no statistically significant differences among the three treatment groups for overall objective tumor response . Patients treated with letrozole 0.5 mg had improvements in disease progression ( P = .044 ) and a decreased risk of treatment failure ( P = .018 ) , compared with patients treated with megestrol acetate . Letrozole 0.5 mg showed a trend ( P = .053 ) for survival benefit when compared with megestrol acetate . Megestrol acetate was more likely to produce weight gain , dyspnea , and vaginal bleeding , and the letrozole groups were more likely to experience headache , hair thinning , and diarrhea . CONCLUSION Given a favorable tolerability profile , once-daily dosing , and evidence of clinical ly relevant benefit , letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens Fulvestrant is an estrogen receptor antagonist with no agonist effects . In the second‐line treatment of advanced breast carcinoma , fulvestrant was shown previously to be as effective as the third‐generation aromatase inhibitor , anastrozole , in terms of time to disease progression and objective response rates . The authors reported the overall survival results from these studies PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in pre clinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were r and omized to 21-day cycles of oral capecitabine 1,250 mg/m(2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m(2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel result ed in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P = .0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P = .0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P = .006 ) compared with docetaxel . Gastrointestinal side effects and h and -foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC PURPOSE Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen . This study was design ed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor ( AI ) . PATIENTS AND METHODS A one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and , at most , one additional hormonal agent . Tumors must have been estrogen receptor and /or progesterone receptor positive . The primary end point was objective response rate , and secondary end points were time to disease progression , survival , duration of response , and toxicity . RESULTS Eighty patients were enrolled , and three were ineligible . Characteristics of the 77 eligible patients included median age of 68 years , performance score of 0 or 1 in 91 % of patients , visceral dominant disease in 88 % of patients , two prior hormonal treatments in 73 % of patients , and prior chemotherapy for metastatic disease in 32 % of patients . Eleven patients ( 14.3 % ) achieved a partial response , and 16 patients ( 20.8 % ) had stable disease for at least 6 months , for a clinical benefit rate of 35 % . Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen . Median time to progression was 3 months , and median survival time was 20.2 months . Fulvestrant was well tolerated . CONCLUSION Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI PURPOSE To compare the efficacy and tolerability of fulvestrant ( formerly ICI 182,780 ) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment . PATIENTS AND METHODS In this double-blind , double-dummy , parallel-group study , postmenopausal patients were r and omized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg . The primary end point was time to progression ( TTP ) . Secondary end points included objective response ( OR ) rate , duration of response ( DOR ) , and tolerability . RESULTS Patients ( n = 400 ) were followed for a median period of 16.8 months . Fulvestrant was as effective as anastrozole in terms of TTP ( hazard ratio , 0.92 ; 95.14 % confidence interval [ CI ] , 0.74 to 1.14 ; P = .43 ) ; median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole . OR rates were 17.5 % with both treatments . Clinical benefit rates ( complete response + partial response + stable disease > or = 24 weeks ) were 42.2 % for fulvestrant and 36.1 % for anastrozole ( 95 % CI , -4.00 % to 16.41 % ; P = .26 ) . In responding patients , median DOR ( from r and omization to progression ) was 19.0 months for fulvestrant and 10.8 months for anastrozole . Using all patients , DOR was significantly greater for fulvestrant compared with anastrozole ; the ratio of average response duration s was 1.35 ( 95 % CI , 1.10 to 1.67 ; P < 0.01 ) . Both treatments were well tolerated . CONCLUSION Fulvestrant was at least as effective as anastrozole , with efficacy end points slightly favoring fulvestrant . Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy BACKGROUND To compare the efficacy , safety and tolerability of letrozole , an advanced non-steroidal aromatase inhibitor , and fadrozole hydrochloride , an older-generation drug in this class , we conducted a r and omised double-blind trial in postmenopausal women with advanced breast cancer . PATIENTS AND METHODS One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and r and omly assigned to receive letrozole or fadrozole in a multicentre , r and omised double-blind trial in Japan . One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily ( n = 77 ) or fadrozole 1.0 mg twice daily ( n = 77 ) , for a minimum of 8 weeks . RESULTS Letrozole showed a significantly higher overall objective response rate [ complete response ( CR ) + partial response ( PR ) ] than fadrozole ( 31.2 % and 13.0 % , respectively ; P = 0.011 , Fisher 's exact test ) . Clinical benefits defined as CR , PR and stable disease ( no change in status for more than 24 weeks ) were also higher in patients treated with letrozole ( 50.6 % ) than fadrozole ( 35.1 % ) . Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue , bone and viscera ( P = 0.011 , stratified Mantel-Haenszel test ) . Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference ( P = 0.175 , log-rank test ) . Letrozole markedly reduced the estradiol , estrone and estrone sulfate levels in peripheral blood within 4 weeks . The suppressive effect of fadrozole on these hormone levels was insufficient . Adverse drug reactions were observed in 35.9 % of the patients treated with letrozole and in 39.5 % of those treated with fadrozole with no significant difference between the two groups ( P = 0.74 , Fisher 's exact test ) . Most of the adverse drug reactions were rated as grade 1 or 2 . CONCLUSIONS The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily , with similar safety and tolerability profiles PURPOSE To compare the efficacy and tolerability of fulvestrant ( formerly ICI 182,780 ) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment . PATIENTS AND METHODS Patients ( n = 451 ) with advanced breast cancer were r and omized to receive fulvestrant 250 mg as a once-monthly ( one x 5 mL ) intramuscular injection or an oral dose of anastrozole 1 mg in this open , parallel-group , multicenter trial . The primary end point was time to progression ( TTP ) . Secondary end points included objective response ( OR ) rates , defined as complete response ( CR ) or partial response ( PR ) , duration of response ( DOR ) , and tolerability . RESULTS Patients were followed for a median period of 14.4 months . In terms of TTP , fulvestrant was as effective as anastrozole ( hazard ratio , 0.98 ; confidence interval [ CI ] , 0.80 to 1.21 ; P = .84 ) . Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole . OR rates showed a numerical advantage for fulvestrant ( 20.7 % ) over anastrozole ( 15.7 % ) ( odds ratio , 1.38 ; CI , 0.84 to 2.29 ; P = .20 ) . Clinical benefit rates ( CR + PR + stable disease > or = 24 weeks ) were 44.6 % for fulvestrant and 45.0 % for anastrozole . Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole . Both treatments were well tolerated , with 3.2 % and 1.3 % of fulvestrant- and anastrozole-treated patients , respectively , withdrawn from treatment because of an adverse event . CONCLUSION Fulvestrant was as effective as anastrozole . These data confirm that fulvestrant is an additional , effective , and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy |
11,220 | 28,989,282 | It also improved IBS severity and other abdominal symptoms such as bloating , discomfort , and risk of urgency and fecal incontinence .
Conclusion Eluxadoline ’s place in clinical practice might prove useful since the pharmacological options of IBS-D are limited and eluxadoline showed a positive effect in treating the symptoms of | Background Irritable bowel syndrome with diarrhea ( IBS-D ) has limited options for treatment currently , including mainly anti-motility medications , antispasmodics , and antidepressants . | BACKGROUND & AIMS Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome ( IBS-D ) . A phase 3 , r and omized , double-blind , placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin . METHODS The trial included adults with IBS-D , mean abdominal pain and bloating scores of 3 or more , and loose stool , located at 270 centers in the United States and Europe from February 2012 through June 2014 . Those responding to a 2-week course of open-label rifaximin 550 mg 3 times daily , who then relapsed during an observation phase ( up to 18 weeks ) , were r and omly assigned to groups given repeat treatments of rifaximin 550 mg or placebo 3 times daily for 2 weeks . The primary end point was percentage of responders after first repeat treatment , defined as a decrease in abdominal pain of ≥30 % from baseline and a decrease in frequency of loose stools of ≥50 % from baseline , for 2 or more weeks during a 4-week post-treatment period . RESULTS Of 1074 patients ( 44.1 % ) who responded to open-label rifaximin , 382 ( 35.6 % ) did not relapse and 692 ( 64.4 % ) did ; of these , 636 were r and omly assigned to receive repeat treatment with rifaximin ( n = 328 ) or placebo ( n = 308 ) . The percentage of responders was significantly greater with rifaximin than placebo ( 38.1 % vs 31.5 % ; P = .03 ) . The percentage of responders for abdominal pain ( 50.6 % vs 42.2 % ; P = .018 ) was significantly greater with rifaximin than placebo , but not stool consistency ( 51.8 % vs 50.0 % ; P = .42 ) . Significant improvements were also noted for prevention of recurrence , durable response , and bowel movement urgency . Adverse event rates were low and similar between groups . CONCLUSIONS In a phase 3 study of patients with relapsing symptoms of IBS-D , repeat rifaximin treatment was efficacious and well tolerated . Clinical Trials.gov ID : NCT01543178 BACKGROUND & AIMS Eluxadoline is approved by the Food and Drug Administration for the treatment of adults with irritable bowel syndrome with diarrhea ( IBS‐D ) . Eluxadoline is a locally acting mixed & mgr;‐opiod and & kgr;‐opioid receptor agonist and & dgr;‐opioid receptor antagonist . The abuse potential of eluxadoline was evaluated as part of the Phase 2 and 3 clinical trials assessing the efficacy , safety , and tolerability of the drug . METHODS One Phase 2 ( IBS‐2001 ) and two Phase 3 ( IBS‐3001 and IBS‐3002 ) r and omized controlled trials enrolled patients meeting Rome III criteria for IBS‐D. Patients received oral twice‐daily double‐blind treatment with eluxadoline or placebo for 12 , 26 , or 52 weeks . The primary end point of these studies was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50 % of days . Safety data were pooled , and specific adverse event terms potentially related to abuse were assessed descriptively . Adverse events reported during a 2‐week post‐treatment period ( IBS‐3001 ) and a 4‐week single‐blind washout period ( IBS‐3002 ) were assessed for signs of opioid withdrawal . Potential withdrawal effects were assessed by using the Subjective Opiate Withdrawal Scale . RESULTS Overall , 807 and 1032 patients received 1 or more doses of eluxadoline ( 75 or 100 mg , respectively ) , and 975 patients received placebo . The overall incidence of adverse events potentially related to abuse did not differ significantly among the groups given placebo , eluxadoline 75 mg , or eluxadoline 100 mg ( 2.8 % , 2.7 % , and 4.3 % , respectively ) . The most common adverse events potentially related to abuse were anxiety and somnolence , which occurred in less than 2 % of patients in each group . Median overall Subjective Opiate Withdrawal Scale scores did not differ significantly among the groups given placebo , eluxadoline 75 mg , or eluxadoline 100 mg ( 3.0 , 2.0 , and 3.0 , respectively ) . CONCLUSIONS In an analysis of data from Phase 2 and Phase 3 trials of eluxadoline ( 75 or 100 mg ) for patients with IBS‐D , data revealed no signs of abuse potential for eluxadoline . Clinical Trials.gov numbers : NCT01130272 , NCT01553591 , NCT01553747 BACKGROUND Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome ( IBS ) . We evaluated rifaximin , a minimally absorbed antibiotic , as treatment for IBS . METHODS In two identically design ed , phase 3 , double-blind , placebo-controlled trials ( TARGET 1 and TARGET 2 ) , patients who had IBS without constipation were r and omly assigned to either rifaximin at a dose of 550 mg or placebo , three times daily for 2 weeks , and were followed for an additional 10 weeks . The primary end point , the proportion of patients who had adequate relief of global IBS symptoms , and the key secondary end point , the proportion of patients who had adequate relief of IBS-related bloating , were assessed weekly . Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment . Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating , abdominal pain , and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study . RESULTS Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment ( 40.8 % vs. 31.2 % , P=0.01 , in TARGET 1 ; 40.6 % vs. 32.2 % , P=0.03 , in TARGET 2 ; 40.7 % vs. 31.7 % , P<0.001 , in the two studies combined ) . Similarly , more patients in the rifaximin group than in the placebo group had adequate relief of bloating ( 39.5 % vs. 28.7 % , P=0.005 , in TARGET 1 ; 41.0 % vs. 31.9 % , P=0.02 , in TARGET 2 ; 40.2 % vs. 30.3 % , P<0.001 , in the two studies combined ) . In addition , significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms , bloating , abdominal pain , and stool consistency . The incidence of adverse events was similar in the two groups . CONCLUSIONS Among patients who had IBS without constipation , treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms , bloating , abdominal pain , and loose or watery stools . ( Funded by Salix Pharmaceuticals ; Clinical Trials.gov numbers , NCT00731679 and NCT00724126 . ) 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 Objectives : Eluxadoline is a mixed μ-opioid receptor ( OR ) and κ-OR agonist and δ-OR antagonist , approved for the treatment of irritable bowel syndrome with diarrhea ( IBS-D ) . This analysis evaluated the safety and tolerability of eluxadoline 75 and 100 mg twice daily ( BID ) in one Phase 2 ( IBS-2001 ) and two Phase 3 ( IBS-3001 and IBS-3002 ) studies . Methods : Adults with IBS-D ( Rome III criteria ) were r and omized to placebo or eluxadoline ( 75 or 100 mg ) BID for 12 ( IBS-2001 ) , 26 ( IBS-3002 ) , or 52 ( IBS-3001 ) weeks . Safety data were pooled . Adverse events ( AEs ) were assessed , with special focus on opioid-related AEs , including suspected sphincter of Oddi spasm ( SOS ) events . Results : 2,776 patients were included in the enrolled set ; the safety set comprised 2,814 patients , based on actual treatments received . The most frequent AEs in the placebo and eluxadoline 75 and 100 mg groups were constipation ( 2.5 , 7.4 , and 8.1 % , respectively ) and nausea ( 5.0 , 8.1 , and 7.1 % , respectively ) ; discontinuation due to constipation was uncommon ( 0.3 , 1.1 , and 1.5 % , respectively ) . Ten SOS events ( 10/1,839 ; 0.5 % ) occurred in eluxadoline-treated patients , manifesting as acute abdominal pain with elevated aminotransferases or lipase , or pancreatitis ; all occurred in patients without a gallbladder . Eight of these events occurred with the higher dose of eluxadoline , within 1 week of initiation of therapy , and all resolved with eluxadoline discontinuation . There were five events independently adjudicated as pancreatitis not associated with SOS , three of which were associated with heavy alcohol use . Conclusions : Eluxadoline was well tolerated in Phase 2 and 3 trials , with constipation and nausea the most common AEs . Consistent with the known adverse effects of opioid agonists , clinical ly apparent SOS events were observed in eluxadoline-treated patients . All occurred in patients without a gallbladder and the majority were observed in patients on the higher dose of eluxadoline , suggesting a possible association OBJECTIVE : There has been growing interest in the investigation of health-related quality of life ( HRQOL ) among patients with gastrointestinal ( GI ) disorders . We recently reported on the development and preliminary validation of the IBS-QOL , a specific quality -of-life measure for irritable bowel syndrome ( IBS ) . The aim of this study was to determine the longitudinal construct validity ( responsiveness ) of the IBS-QOL . METHODS : Female patients enrolled in a multicenter treatment trial for functional bowel disorders were studied pre- and posttreatment with the IBS-QOL and other health status measures . Based on the response to treatment for several variables ( pain/14-day score , daily function , and days in bed/3 months ) , patients were stratified into Responders , Partial Responders , and Nonresponders . Change scores in the IBS-QOL were then statistically compared with changes in the other variables to determine their correlation and whether Responders were significantly different from non- and Partial Responders on the IBS-QOL . RESULTS : There was a significant correlation between change scores on the IBS-QOL and the other measures of treatment effect ( Pain/14 days , r = 0.25 , p < 0.002 ; Sickness Impact Profile [ SIP ] Total Score , r = 0.28 , p < 0.0004 ) . In addition , the IBS-QOL scores significantly differentiated Responders from Nonresponders for most of the variables tested ( regression trend test for Pain/14 days , p < 0.04 ; SIP Total , p < 0.0001 ; SIP Physical , p < 0.0001 ; SIP Psychosocial , p < 0.002 , and SIP Eating , p < 0.04 ) . CONCLUSION : The IBS-QOL is responsive to treatment in a referral-based clinical population of patients with functional bowel disorders The mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist , eluxadoline , is licensed in the USA for the treatment of irritable bowel syndrome with diarrhoea ( IBS‐D ) , based on the results of two large Phase 3 clinical trials Effects of the currently marketed form of loperamide ( Imodium capsules ) that might relate to abuse potential were examined . Study I was a double‐blind “ dose run‐up ” in adult male subjects with a history of illicit drug use but no history of opioid addiction . Subjective responses to doses of loperamide ranging from 12 to 60 mg were compared with responses to 120 mg codeine sulfate ( 96 mg base ) and to placebo . Based on study I , loperamide ( 60 mg ) was used in study II and its effects were compared with those of codeine ( 96 mg base ) and placebo in an exaddict subject group . Study II subjects had had extensive opioid experience but were not actively addicted at the time of this double‐blind , inpatient study . In study II , as in study I , unlike loperamide and placebo , codeine induced pupillary constriction . Loperamide ( 60 mg ) induced a detectable subjective effect in somewhat over half the subjects , was “ liked ” little or not at all , and was identified as “ dope ” at a frequency less than that for a threshold dose of oral codeine . It was concluded that in its present form , i.e. , capsules containing loperamide mixed with magnesium stearate , loperamide poses little threat of potential abuse Objectives : Irritable bowel syndrome with diarrhea ( IBS-D ) is often managed with over-the-counter therapies such as loperamide , though with limited success . This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies . Methods : Adults with IBS-D ( Rome III criteria ) were enrolled and r and omized to placebo or eluxadoline ( 75 or 100 mg ) twice daily for 26 ( IBS-3002 ) or 52 ( IBS-3001 ) weeks . Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies . The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea . Results : A total of 2,428 patients were enrolled ; 36.0 % reported prior loperamide use , of whom 61.8 % reported prior inadequate IBS-D symptom control with loperamide . Among patients with prior loperamide use , a greater proportion treated with eluxadoline ( 75 and 100 mg ) were composite responders vs. those treated with placebo with inadequate prior symptom control , over weeks 1–12 ( 26.3 % ( P=0.001 ) and 27.0 % ( P<0.001 ) vs. 12.7 % , respectively ) ; similar results were observed over weeks 1–26 . When daily rescue loperamide use was imputed as a nonresponse day , the composite responder rate was still higher in patients receiving eluxadoline ( 75 and 100 mg ) vs. placebo over weeks 1–12 ( P<0.001 ) and weeks 1–26 ( P<0.001 ) . Adverse events included nausea and abdominal pain . Conclusions : Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment , with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment Background Effective and safe treatments are needed for patients who have irritable bowel syndrome ( IBS ) with diarrhea . We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline , a new oral agent with mixed opioid effects ( μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist ) , in patients with IBS with diarrhea . Methods We r and omly assigned 2427 adults who had IBS with diarrhea to eluxadoline ( at a dose of 75 mg or 100 mg ) or placebo twice daily for 26 weeks ( IBS-3002 trial ) or 52 weeks ( IBS-3001 trial ) . The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50 % of the days from weeks 1 through 12 and from weeks 1 through 26 . Results For weeks 1 through 12 , more patients in the eluxadoline groups ( 75 mg and 100 mg ) than in the placebo group reached the primary end point ( IBS-3001 trial , 23.9 % with the 75-mg dose and 25.1 % with the 100-mg dose vs. 17.1 % with placebo ; P=0.01 and P=0.004 , respectively ; IBS-3002 trial , 28.9 % and 29.6 % , respectively , vs. 16.2 % ; P<0.001 for both comparisons ) . For weeks 1 through 26 , the corresponding rates in IBS-3001 were 23.4 % and 29.3 % versus 19.0 % ( P=0.11 and P<0.001 , respectively ) , and the corresponding rates in IBS-3002 were 30.4 % and 32.7 % versus 20.2 % ( P=0.001 and P<0.001 , respectively ) . The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline , as compared with placebo , were nausea ( 8.1 % and 7.5 % vs. 5.1 % ) , constipation ( 7.4 % and 8.6 % vs. 2.5 % ) , and abdominal pain ( 5.8 % and 7.2 % vs. 4.1 % ) . Pancreatitis developed in 5 ( 2 in the 75-mg group and 3 in the 100-mg group ) of the 1666 patients in the safety population ( 0.3 % ) . Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women , with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily . ( Funded by Furiex Pharmaceuticals , an affiliate of Allergan ; IBS-3001 and IBS-3002 Clinical Trials.gov numbers , NCT01553591 and NCT01553747 , respectively . ) BACKGROUND & AIMS Simultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea ( IBS-D ) without constipating side effects . We evaluated the efficacy and safety of a minimally absorbed , μ-opioid receptor agonist and δ-opioid receptor antagonist ( eluxadoline ) in a phase 2 study in patients with IBS-D. METHODS We r and omly assigned 807 patients to groups that received oral placebo twice daily or 5 , 25 , 100 , or 200 mg oral eluxadoline for 12 weeks . The primary end point was clinical response at week 4 , defined by a mean reduction in daily pain score from baseline of ≥ 30 % , and of at least 2 points on 0 - 10 scale , as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale ( 1 - 7 ) for at least 66 % of daily diary entries during that week . RESULTS Significantly more patients receiving 25 mg ( 12.0 % ) or 200 mg ( 13.8 % ) eluxadoline met the primary end point of clinical response than patients given placebo ( 5.7 % ; P < .05 ) . Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency , global symptoms , quality of life , and adequate relief assessment s ( P < .05 ) . Additionally , patients receiving 100 mg ( 28.0 % ) or 200 mg ( 28.5 % ) eluxadoline were significantly more likely than those receiving placebo ( 13.8 % ; P < .005 ) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study . Eluxadoline was well tolerated with a low incidence of constipation . CONCLUSIONS In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D , patients given eluxadoline were significantly more likely to be clinical responders , based on a composite of improvement in abdominal pain and stool consistency . Further study of eluxadoline is warranted to assess its potential as a treatment for |
11,221 | 25,412,265 | Extrusion was the most difficult movement to control ( 30 % of accuracy ) , followed by rotation .
CAT aligns and levels the arches ; it is effective in controlling anterior intrusion but not anterior extrusion ; it is effective in controlling posterior buccolingual inclination but not anterior buccolingual inclination ; it is effective in controlling upper molar bodily movements of about 1.5 mm ; and it is not effective in controlling rotation of rounded teeth in particular . | OBJECTIVE To assess the scientific evidence related to the efficacy of clear aligner treatment ( CAT ) in controlling orthodontic tooth movement . | OBJECTIVE To evaluate the influence of attachments and interproximal reduction on canines undergoing rotational movement with Invisalign . MATERIAL S AND METHODS In this prospect i ve clinical study , 53 canines ( 33 maxillary and 20 m and ibular ) were measured from the virtual TREAT models of 31 participants treated with anterior Invisalign . The pretreatment virtual model of the predicted final tooth position was superimposed on the posttreatment virtual model using ToothMeasure , Invisalign 's proprietary measurement software . A one-way analysis of variance ( ANOVA ) ( P < .05 ) compared three treatment modalities : attachments only ( AO ) , interproximal reduction only ( IO ) , and neither attachments nor interproximal reduction ( N ) . Student 's t-tests ( P < .05 ) compared the mean accuracy of canine rotation between arches . RESULTS The mean accuracy of canine rotation with Invisalign was 35.8 % ( SD = 26.3 ) . Statistical analyses indicated that there was no significant difference in accuracy between groups AO , IO , and N ( P = .343 ) . There was no statistically significant difference ( P = .888 ) in rotational accuracy for maxillary and m and ibular canines for any of the treatment groups . The most commonly prescribed attachment shape was the vertical-ellipsoid ( 70.5 % ) . CONCLUSIONS Vertical-ellipsoid attachments and interproximal reduction do not significantly improve the accuracy of canine rotation with the Invisalign system OBJECTIVE Based on our previous pilot study , the objective of this extended study was to compare ( a ) casts to their corresponding digital ClinCheck ® models at baseline and ( b ) the tooth movement achieved at the end of aligner therapy ( Invisalign ® ) to the predicted movement in the anterior region . MATERIAL S AND METHODS Pre- and post-treatment casts as well as initial and final ClinChecks ® models of 50 patients ( 15 - 63 years of age ) were analyzed . All patients were treated with Invisalign ® ( Align Technology , Santa Clara , CA , USA ) . Evaluated parameters were : upper/lower anterior arch length and intercanine distance , overjet , overbite , dental midline shift , and the irregularity index according to Little . The comparison achieved/predicted tooth movement was tested for equivalence [ adjusted 98.57 % confidence interval ( - 1.00 ; + 1.00 ) ] . RESULTS Before treatment the anterior crowding , according to Little , was on average 5.39 mm ( minimum 1.50 mm , maximum 14.50 mm ) in the upper dentition and 5.96 mm ( minimum 2.00 mm , maximum 11.50 mm ) in the lower dentition . After treatment the values were reduced to 1.57 mm ( minimum 0 mm , maximum 4.5 mm ) in the maxilla and 0.82 mm ( minimum 0 mm , maximum 2.50 mm ) in the m and ible . We found slight deviations between pretreatment casts and initialClinCheck ® ranging on average from -0.08 mm ( SD ± 0.29 ) for the overjet and up to -0.28 mm ( SD ± 0.46 ) for the upper anterior arch length . The difference between achieved/predicted tooth movements ranged on average from 0.01 mm ( SD ± 0.48 ) for the lower anterior arch length , up to 0.7 mm ( SD ± 0.87 ) for the overbite . All parameters were significantly equivalent except for the overbite ( -1.02 ; -0.39 ) . CONCLUSION Performed with aligners ( Invisalign ® ) , the resolvement of the partly severe anterior crowding was successfully accomplished . Resolving lower anterior crowding by protrusion of the anterior teeth ( i.e. , enlargement of the anterior arch length ) seems well predictable . The initial ClinCheck ® models provided high accuracy compared to the initial casts . The achieved tooth movement was in concordance with the predicted movement for all parameters , except for the overbite Clear aligners provide a convenient model to measure orthodontic tooth movement ( OTM ) . We examined the role of in vivo aligner material fatigue and subject-specific factors in tooth movement . Fifteen subjects seeking orthodontic treatment at the University of Florida were enrolled . Results were compared with data previously collected from 37 subjects enrolled in a similar protocol . Subjects were followed prospect ively for eight weeks . An upper central incisor was programmed to move 0.5 mm . every two weeks using clear aligners . A duplicate aligner was provided for the second week of each cycle . Weekly polyvinyl siloxane ( PVS ) impressions were taken , and digital models were fabricated to measure OTM . Initial and final cone beam computed tomography ( CBCT ) images were obtained to characterize OTM . Results were compared to data from a similar protocol , where subjects received a new aligner biweekly . No significant difference was found in the amount of OTM between the two groups , with mean total OTM of 1.11 mm . ( st and ard deviation ( SD ) 0.30 ) and 1.07 mm . ( SD 0.33 ) for the weekly aligner and biweekly control groups , respectively ( P = 0.72 ) . Over eight weeks , in two-week intervals , material fatigue does not play a significant role in the rate or amount of tooth movement Fifty-one patients were enrolled in this study to explore the treatment effects of material stiffness and frequency of appliance change when using clear , sequential , removable appliances ( aligners ) . Patients were stratified based on pretreatment peer assessment rating ( PAR ) scores and need for extraction s. They were r and omized into 4 treatment protocol s : 1-week activation with soft material , 1-week activation with hard material , 2-week activation with soft material , and 2-week activation with hard material . Patients continued with their protocol s until either the series of aligners was completed , or until it was determined that the aligner was not fitting well ( study end point ) . Weighted PAR score and average incisor irregularity ( AII ) indexes were used to measure pretreatment and end-point study models , and average improvement was compared among the 4 groups . In addition to the evaluation of the 4 treatment groups , comparisons were made of the individual components of the PAR score to determine which occlusal components experienced the most correction with the aligners . The percentages and absolute extraction space closures were evaluated , and papillary bleeding scores before and during treatment were compared . Although no statistical difference was observed between the 4 treatment groups , a trend was noted with the 2-week frequency having a larger percentage of reduction in weighted PAR and AII scores , and greater extraction space closure . Anterior alignment was the most improved component , and buccal occlusion was the least improved . When analyzed by type of extraction , incisor extraction sites had a significantly greater percentage of closure than either maxillary or m and ibular premolar extraction sites . A statistically significant decrease in mean average papillary bleeding score was found during treatment when compared with pretreatment scores , although this difference was not clinical ly significant The purpose of this study was to compare the efficacy of overbite correction achieved by a conventional continuous arch wire technique and the segmented arch technique as recommended by Burstone . The sample comprised 50 adult patients ( age 18 to 40 years ) with deep bites . Twenty-five patients were treated with a continuous arch wire technique ( CAW ) ; in the second half of the sample , the segmented arch technique ( Burstone ) was used for correction of the vertical malocclusion . Lateral cephalograms and plaster cast models taken before and immediately after treatment were evaluated . Statistical analysis was performed on the collected data . The results showed that both techniques produced a highly significant overbite reduction ( CAW : -3.17 mm , p < 0.001 ; Burstone : -3.56 mm , p < 0.001 ) . The CAW group showed an extrusion in the molar area with subsequent posterior rotation of the m and ible ( 6occl-ML : + 1.30 mm ; 6occl-NSL : + 1.63 mm ; ML/NSL : + 1.94 degrees , all p < 0.001 ) . The Burstone group , however , showed overbite reduction by incisor intrusion without any substantial extrusion of posterior teeth ( upper 1-NSL : -1.50 mm ; lower 1-ML : -1.72 mm ; both p < 0.001 ) . As a consequence , no significant posterior rotation of the m and ible took place ( ML/NSL : + 0.52 degrees , n.s . ) . It is concluded that in adult patients the segmented arch technique ( Burstone ) can be considered as being superior to a conventional continuous arch wire technique if arch leveling by incisor intrusion is indicated |
11,222 | 27,537,281 | RESULTS In the aggregate , achieving high effective coverage for this set of interventions would very substantially reduce risk for our outcomes of interest and reduce outcome inequities .
Behavioral interventions targeting practice s at birth and in the hours that follow can have substantial impact in setting s where many births happen at home : in such circumstances early initiation of breastfeeding can reduce risk of newborn death by up to 20 % ; good thermal care practice s can reduce mortality risk by a similar order of magnitude .
Simple interventions delivered during pregnancy have considerable potential impact on important mortality outcomes . | BACKGROUND Although this is beginning to change , the content of antenatal care has been relatively neglected in safe-motherhood program efforts .
This appears in part to be due to an unwarranted belief that interventions over this period have far less impact than those provided around the time of birth .
In this par , we review available evidence for 21 interventions potentially deliverable during pregnancy at high coverage to neglected population s in low income countries , with regard to effectiveness in reducing risk of : maternal mortality , newborn mortality , stillbirth , prematurity and intrauterine growth restriction . | Background Pakistan has high maternal mortality , particularly in the rural areas . The delay in decision making to seek medical care during obstetric emergencies remains a significant factor in maternal mortality . Methods We present results from an experimental study in rural Pakistan . Village clusters were r and omly assigned to intervention and control arms ( 16 clusters each ) . In the intervention clusters , women were provided information on safe motherhood through pictorial booklets and audiocassettes ; traditional birth attendants were trained in clean delivery and recognition of obstetric and newborn complications ; and emergency transportation systems were set up . In eight of the 16 intervention clusters , husb and s also received specially design ed education material s on safe motherhood and family planning . Pre- and post-intervention surveys on selected maternal and neonatal health indicators were conducted in all 32 clusters . A district-wide survey was conducted two years after project completion to measure any residual impact of the interventions . Results Pregnant women in intervention clusters received prenatal care and prophylactic iron therapy more frequently than pregnant women in control clusters . Providing safe motherhood education to husb and s result ed in further improvement of some indicators . There was a small but significant increase in percent of hospital deliveries but no impact on the use of skilled birth attendants . Perinatal mortality reduced significantly in clusters where only wives received information and education in safe motherhood . The survey to assess residual impact showed similar results . Conclusions We conclude that providing safe motherhood education increased the probability of pregnant women having prenatal care and utilization of health services for obstetric complications Abstract Objective To evaluate whether routine administration of sublingual misoprostol 600 μg after delivery reduces postpartum haemorrhage . Design R and omised double blind placebo controlled trial . Setting Primary health centre in Bissau , Guinea-Bissau , West Africa . Participants 661 women undergoing vaginal delivery . Intervention Misoprostol 600 μg or placebo administered sublingually immediately after delivery . Main outcome measures Postpartum haemorrhage , defined as a loss of ≥ 500 ml and decrease in haemoglobin concentration after delivery . Results The incidence of postpartum haemorrhage was not significantly different between the two groups , the relative risk being 0.89 ( 95 % confidence interval 0.76 to 1.04 ) in the misoprostol group compared with the placebo group . Mean blood loss was 10.5 % ( −0.5 % to 20.4 % ) lower in the misoprostol group than in the control group . Severe postpartum haemorrhage of ≥ 1000 ml or ≥1500 ml occurred in 17 % ( 56 ) and 8 % ( 25 ) in the placebo group and 11 % ( 37 ) and 2 % ( 7 ) in the misoprostol group . Significantly fewer women in the misoprostol group experienced a loss of ≥1000 ml ( 0.66 , 0.45 to 0.98 ) or ≥ 1500 ml ( 0.28 , 0.12 to 0.64 ) . The decrease in haemoglobin concentration tended to be less in the misoprostol group , the mean difference between the two groups being 0.16 mmol/l ( −0.01 mmol/l to 0.32 mmol/l ) . Conclusion Sublingual misoprostol reduces the frequency of severe postpartum haemorrhage David Osrin and colleagues report findings from a cluster-r and omized trial conducted in Mumbai slums ; the trial aim ed to evaluate whether facilitator-supported women 's groups could improve perinatal outcomes WHO recommends that anthelmintic treatment be included in strategies to improve maternal nutrition in areas where hookworms are endemic and anaemia is prevalent . At present , few countries have adopted this recommendation , partly owing to the lack of data to support the adverse effects of hookworms on maternal health . A longitudinal study was conducted on 125 women in Sierra Leone ( in 1995/96 ) to measure the impact of single-dose albendazole ( 400 mg ) and daily iron-folate supplements ( 36 mg iron and 5 mg folate ) on haemoglobin and serum ferritin concentration during pregnancy . Women who received both albendazole and iron-folate supplements experienced no significant change ( P > 0.05 ) in the prevalence of anaemia and iron-deficiency anaemia between the first and third trimesters . These prevalence levels significantly increased ( P < 0.05 ) in women who received either albendazole or iron-folate supplements or neither . After controlling for baseline haemoglobin concentration and season , the mean decline in haemoglobin concentration between the first and third trimester in women who received albendazole was 6.6 g/L less than in women who received the control ( P = 0.0034 ) . The corresponding value for iron-folate supplements was 13.7 g/L haemoglobin ( P < 0.001 ) . The effects of albendazole and iron-folate supplements were additive . These findings lend support to WHO 's recommendation for anthelmintic treatment during pregnancy BACKGROUND More than 95 % of neonatal deaths occur in developing countries , approximately 50 % at home . Few data are available on the impact of h and -washing practice s by birth attendants or caretakers on neonatal mortality . OBJECTIVE To evaluate the relationship between birth attendant and maternal h and -washing practice s and neonatal mortality in rural Nepal . DESIGN Observational prospect i ve cohort study . SETTING Sarlahi District in rural southern Nepal . PARTICIPANTS Newborn infants were originally enrolled in a community-based trial assessing the effect of skin and /or umbilical cord cleansing with chlorhexidine on neonatal mortality in southern Nepal . A total of 23,662 newborns were enrolled and observed through 28 days of life . MAIN EXPOSURES Question naires were administered to mothers on days 1 and 14 after delivery to identify care practice s and risk factors for mortality and infection . Three h and -washing categories were defined : ( 1 ) birth attendant h and washing with soap and water before assisting with delivery , ( 2 ) maternal h and washing with soap and water or antiseptic before h and ling the baby , and ( 3 ) combined birth attendant and maternal h and washing . OUTCOME MEASURES Mortality within the neonatal period . RESULTS Birth attendant h and washing was related to a statistically significant lower mortality rate among neonates ( adjusted relative risk [ RR ] = 0.81 ; 95 % confidence interval [ CI ] , 0.66 - 0.99 ) , as was maternal h and washing ( adjusted RR = 0.56 ; 95 % CI , 0.38 - 0.82 ) . There was a 41 % lower mortality rate among neonates exposed to both h and -washing practice s ( adjusted RR = 0.59 ; 95 % CI , 0.37 - 0.94 ) . CONCLUSIONS Birth attendant and maternal h and washing with soap and water were associated with significantly lower rates of neonatal mortality . Measures to improve or promote birth attendant and maternal h and washing could improve neonatal survival rates OBJECTIVES To determine the effectiveness of birth plans in increasing use of skilled care at delivery and in the postnatal period among antenatal care ( ANC ) attendees in a rural district with low occupancy of health units for delivery but high antenatal care uptake in northern Tanzania . METHODS Cluster r and omised trial in Ngorongoro district , Arusha region , involving 16 health units ( 8 per arm ) . Nine hundred and five pregnant women at 24 weeks of gestation and above ( 404 in the intervention arm ) were recruited and followed up to at least 1 month postpartum . RESULTS Skilled delivery care uptake was 16.8 % higher in the intervention units than in the control [ 95 % CI 2.6 - 31.0 ; P = 0.02 ] . Postnatal care utilisation in the first month of delivery was higher ( difference in proportions : 30.0 % [ 95 % CI 1.3 - 47.7 ; P < 0.01 ] ) and also initiated earlier ( mean duration 6.6 ± 1.7 days vs. 20.9 ± 4.4 days , P < 0.01 ) in the intervention than in the control arm . Women 's and providers ' reports of care satisfaction ( received or provided ) did not differ greatly between the two arms of the study ( difference in proportion : 12.1 % [ 95 % CI -6.3 - 30.5 ] P = 0.17 and 6.9 % [ 95 % CI -3.2 - 17.1 ] P = 0.15 , respectively ) . CONCLUSION Implementation of birth plans during ANC can increase the uptake of skilled delivery and post delivery care in the study district without negatively affecting women 's and providers ' satisfaction with available ANC services . Birth plans should be considered along with the range of other recommended interventions as a strategy to improve the uptake of maternal health services BACKGROUND Most mothers breastfeed in Bangladesh , but they rarely practise exclusive breastfeeding . Hospital-based strategies for breastfeeding promotion can not reach them because about 95 % have home deliveries . We postulated that with the intervention of trained peer counsellors , mothers could be enabled to breastfeed exclusively for the recommended duration of 5 months . METHODS 40 adjacent zones in Dhaka were r and omised to intervention or control groups . Women were enrolled during the last trimester of pregnancy between February and December , 1996 . In the intervention group , 15 home-based counselling visits were scheduled , with two visits in the last trimester , three early postpartum ( within 48 h , on day 5 , between days 10 and 14 ) , and fortnightly thereafter until the infant was 5 months old . Peer counsellors were local mothers who received 10 days ' training . FINDINGS 363 women were enrolled in each group . Peer counselling significantly improved breastfeeding practice s. For the primary outcome , the prevalence of exclusive breastfeeding at 5 months was 202/228 ( 70 % ) for the intervention group and 17/285 ( 6 % ) for the control group ( difference=64 % ; 95 % CI 57%-71 % , p>0.0001 ) . For the secondary outcomes , mothers in the intervention group initiated breastfeeding earlier than control mothers and were less likely to give prelacteal and postlacteal foods . At day 4 , significantly more mothers in the intervention group breastfed exclusively than controls . INTERPRETATION Peer counsellors can effectively increase the initiation and duration of exclusive breastfeeding . We recommend incorporation of peer counsellors in mother and child health programmes in developing countries Background In the global context of a reduction of under-five mortality , neonatal mortality is an increasingly relevant component of this mortality . Malaria in pregnancy may affect neonatal survival , though no strong evidence exists to support this association . Methods In the context of a r and omised , placebo-controlled trial of intermittent preventive treatment ( IPTp ) with sulphadoxine-pyrimethamine ( SP ) in 1030 Mozambican pregnant women , 997 newborns were followed up until 12 months of age . There were 500 live borns to women who received placebo and 497 to those who received SP . Findings There were 58 infant deaths ; 60.4 % occurred in children born to women who received placebo and 39.6 % to women who received IPTp ( p = 0.136 ) . There were 25 neonatal deaths ; 72 % occurred in the placebo group and 28 % in the IPTp group ( p = 0.041 ) . Of the 20 deaths that occurred in the first week of life , 75 % were babies born to women in the placebo group and 25 % to those in the IPTp group ( p = 0.039 ) . IPTp reduced neonatal mortality by 61.3 % ( 95 % CI 7.4 % , 83.8 % ) ; p = 0.024 ] . Conclusions Malaria prevention with SP in pregnancy can reduce neonatal mortality . Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group . Alternatively , SP may have reduced the risk of neonatal infections . These findings are of relevance to promote the implementation of IPTp with SP , and provide insights into the underst and ing of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health . Trial Registration Clinical Trials.gov Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh . Methods A cluster-r and omized controlled trial was conducted in Mirzapur , Bangladesh . Twelve unions were r and omized to intervention or comparison arm . All women of reproductive age were eligible to participate . In the intervention arm , community health workers identified pregnant women ; made two antenatal home visits to promote birth and newborn care preparedness ; made four postnatal home visits to negotiate preventive care practice s and to assess newborns for illness ; and referred sick neonates to a hospital and facilitated compliance . Primary outcome measures were antenatal and immediate newborn care behaviours , knowledge of danger signs , care seeking for neonatal complications , and neonatal mortality . Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm , respectively . High coverage of antenatal ( 91 % visited twice ) and postnatal ( 69 % visited on days 0 or 1 ) home visitations was achieved . Indicators of care practice s and knowledge of maternal and neonatal danger signs improved . Adjusted mortality hazard ratio in the intervention arm , compared to the comparison arm , was 1.02 ( 95 % CI : 0.80–1.30 ) at baseline and 0.87 ( 95 % CI : 0.68–1.12 ) at endline . Primary causes of death were birth asphyxia ( 49 % ) and prematurity ( 26 % ) . No adverse events associated with interventions were reported . Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation , and improvements in targeted newborn care practice s suggests the intervention did not adequately address risk factors for mortality . The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions . Programs must ensure skilled care during childbirth , including management of birth asphyxia and prematurity , and curative postnatal care during the first two days of life , in addition to essential newborn care and infection prevention and management . Trial Registration Clinical trials.gov BACKGROUND Strong associations between delayed initiation of breastfeeding and increased neonatal mortality ( 2 - 28 d ) were recently reported in rural Ghana . Investigation into the biological plausibility of this relation and potential causal pathways is needed . OBJECTIVE The objective was to assess the effect of early infant feeding practice s ( delayed initiation , prelacteal feeding , established neonatal breastfeeding ) on infection-specific neonatal mortality in breastfed neonates aged 2 - 28 d. DESIGN This prospect i ve observational cohort study was based on 10 942 breastfed singleton neonates born between 1 July 2003 and 30 June 2004 , who survived to day 2 , and whose mothers were visited in the neonatal period . Verbal autopsies were used to ascertain the cause of death . RESULTS One hundred forty neonates died from day 2 to day 28 ; 93 died of infection and 47 of noninfectious causes . The risk of death as a result of infection increased with increasing delay in initiation of breastfeeding from 1 h to day 7 ; overall late initiation ( after day 1 ) was associated with a 2.6-fold risk [ adjusted odds ratio ( adj OR ) : 2.61 ; 95 % CI : 1.68 , 4.04 ] . Partial breastfeeding was associated with a 5.7-fold adjusted risk of death as a result of infectious disease ( adj OR : 5.73 ; 95 % CI : 2.75 , 11.91 ) . No obvious associations were observed between these feeding practice s and noninfection-specific mortality . Prelacteal feeding was not associated with infection ( adj OR : 1.11 ; 95 % CI : 0.66 , 1.86 ) or noninfection-specific ( adj OR : 1.33 ; 95 % CI : 0.55 , 3.22 ) mortality . CONCLUSIONS This study provides the first epidemiologic evidence of a causal association between early breastfeeding and reduced infection-specific neonatal mortality in young human infants Initiation of breast-feeding within 1 h after birth has been associated with reduced neonatal mortality in a rural Ghanaian population . In South Asia , however , breast-feeding patterns and low birth weight rates differ and this relationship has not been quantified . Data were collected during a community-based r and omized trial of the impact of topical chlorhexidine antisepsis interventions on neonatal mortality and morbidity in southern Nepal . In-home visits were conducted on d 1 - 4 , 6 , 8 , 10 , 12 , 14 , 21 , and 28 to collect longitudinal information on timing of initiation and pattern of breast-feeding . Multivariable regression modeling was used to estimate the association between death and breast-feeding initiation time . Analysis was based on 22,838 breast-fed newborns surviving to 48 h. Within 1 h of birth , 3.4 % of infants were breast-fed and 56.6 % were breast-fed within 24 h of birth . Partially breast-fed infants ( 72.6 % ) were at higher mortality risk [ relative risk ( RR ) = 1.77 ; 95 % CI = 1.32 - 2.39 ] than those exclusively breast-fed . There was a trend ( P = 0.03 ) toward higher mortality with increasing delay in breast-feeding initiation . Mortality was higher among late ( > or = 24 h ) compared with early ( < 24 h ) initiators ( RR = 1.41 ; 95 % CI = 1.08 - 1.86 ) after adjustment for low birth weight , preterm birth , and other covariates . Improvements in breast-feeding practice s in this setting may reduce neonatal mortality substantially . Approximately 7.7 and 19.1 % of all neonatal deaths may be avoided with universal initiation of breast-feeding within the first day or hour of life , respectively . Community-based breast-feeding promotion programs should remain a priority , with renewed emphasis on early initiation in addition to exclusiveness and duration of breast-feeding Exclusive breast-feeding ( EBF ) rates remain low despite numerous health benefits associated with this behavior . We conducted a r and omized trial on the effect of lactation counseling on EBF , which controlled for the Hawthorne effect while also varying the timing of the intervention . Pregnant women attending prenatal clinics in Tema were r and omly assigned to 1 of 2 intervention groups ( IG ) or to a control group ( C ) , as follows : 1 ) EBF support given pre- , peri- , and postnatally ( IG1 ; n = 43 ) ; 2 ) EBF support given only peri- and postnatally ( IG2 ; n = 44 ) ; or 3 ) nonbreast-feeding health educational support ( C ; n = 49 ) that had an equal amount of contact with lactation counselors . Two educational sessions were provided prenatally , and 9 home follow-up visits were provided in the 6-mo postpartum period . Infant feeding data were collected monthly at the participant 's home . The 3 groups did not differ in sociodemographic characteristics . At 6 mo postpartum , 90.0 % in IG1 and 74.4 % in IG2 had exclusively breast-fed during the previous month . By contrast , only 47.7 % in C were doing so ( P = 0.008 ) . Similarly , the percentage of EBF during the 6 mo was significantly higher ( P = 0.02 ) among IG1 and IG2 ( 39.5 % ) than among C ( 19.6 % ) . The 100 % increase in EBF rates can be attributed to the lactation counseling provided . Additional prenatal EBF support may not be needed within a context of strong routine prenatal EBF education BACKGROUND The effect of vitamin A supplementation on the survival of infants aged < 6 mo is unclear . Because most infant deaths occur in the first few month of life , maternal supplementation may improve infant survival . OBJECTIVES The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants < 6 mo of age . DESIGN Married women of reproductive age in 270 wards of Sarlahi district , Nepal , were eligible to participate . Wards were r and omly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate ( vitamin A ) , 42 mg all-trans-beta-carotene , or placebo . Pregnancies were followed until miscarriage , stillbirth , maternal death , or live birth of one or more infants , who were followed through 24 wk of age . RESULTS A total of 43559 women were enrolled ; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial . The rate of fetal loss was 92.0/1000 pregnancies in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.06 ( 95 % CI : 0.91 , 1.25 ) and 1.03 ( 95 % CI : 0.87 , 1.19 ) , respectively . The 24-wk mortality rate was 70.8/1000 live births in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.05 ( 95 % CI : 0.87 , 1.25 ) and 1.03 ( 95 % CI : 0.86 , 1.22 ) , respectively . CONCLUSIONS Small weekly doses of vitamin A or beta-carotene given to women before conception , during pregnancy , and through 24 wk postpartum did not improve fetal or early infant survival in Nepal BACKGROUND We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15 % . OBJECTIVE We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality . DESIGN The study was a double-blind , cluster-r and omized , controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal . In addition to vitamin A ( 1000 microg retinol equivalents ) , the intervention groups received either folic acid ( FA ; 400 microg ) , FA + iron ( 60 mg ) , FA + iron + zinc ( 30 mg ) , or multiple micronutrients ( MNs ; the foregoing plus 10 microg vitamin D , 10 mg vitamin E , 1.6 mg thiamine , 1.8 mg riboflavin , 2.2 mg vitamin B-6 , 2.6 microg vitamin B-12 , 100 mg vitamin C , 64 microg vitamin K , 20 mg niacin , 2 mg Cu , and 100 mg Mg ) . The control group received vitamin A only . RESULTS None of the supplements reduced fetal loss . Compared with control infants , infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15 - 20 % lower 3-mo mortality ; this pattern was not observed with MNs . The effect on mortality was restricted to preterm infants , among whom the relative risks ( RRs ) were 0.36 ( 95 % CI : 0.18 , 0.75 ) for FA , 0.53 ( 0.30 , 0.92 ) for FA + iron , 0.77 ( 0.45 , 1.32 ) for FA + iron + zinc , and 0.70 ( 0.41 , 1.17 ) for MNs . Among term infants , the RR for mortality was close to 1 for all supplements except MNs ( RR : 1.74 ; 95 % CI : 1.00 , 3.04 ) . CONCLUSIONS Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality . Among preterm infants , FA alone or with iron reduced mortality in the first 3 mo of life . MNs may increase mortality risk among term infants , but this effect needs further evaluation BACKGROUND Young infants are at risk of vitamin A deficiency . Supplementation of breastfeeding mothers improves the vitamin A status of their infants , but there are no data regarding its effect on infant mortality , and data on the effect of directly supplementing infants during the first few weeks of life are conflicting . OBJECTIVE The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single , large doses of vitamin A during the immediate postpartum period . DESIGN A r and omized , placebo-controlled , 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants ; 9208 of the mothers were HIV-negative at delivery , remained such during the postpartum year , and were retained in the current analysis . The infants were r and omly assigned within 96 h of delivery to 1 of 4 treatment groups : mothers and infants received vitamin A ( Aa ) , mothers received vitamin A and infants received placebo ( Ap ) , mothers received placebo and infants received vitamin A ( Pa ) , and both mothers and infants received placebo ( Pp ) . The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU . The mother-infant pairs were followed to 12 mo . RESULTS Hazard ratios ( 95 % CI ) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 ( 0.87 , 1.58 ) and 1.08 ( 0.80 , 1.46 ) , respectively . Hazard ratios ( 95 % CI ) for the Aa , Ap , and Pa groups compared with the Pp group were 1.28 ( 0.83 , 1.98 ) , 1.27 ( 0.82 , 1.97 ) , and 1.18 ( 0.76 , 1.83 ) , respectively . These data indicate no overall effect . Serum retinol concentrations among a sub sample of women were similar to reference norms . CONCLUSION Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status Night blindness occurs commonly among women during pregnancy in rural NEPAL : We examined the relationship between maternal night blindness and the risk of mortality occurring among infants in the first 6 mo of life . Stratified analysis by maternal night blindness status during pregnancy was done for 10,000 women participating in a r and omized , placebo-controlled trial of vitamin A and beta-carotene supplementation . Mortality of infants of non-night blind women in all three supplementation groups was similar , and when combined , was 63/1000 live births . Relative to this , mortality was higher by 63 % [ 95 % confidence interval ( CI ) : 9 - 138 % ) and 50 % ( 95 % CI : -3 to 133 % ) among infants of night blind women receiving placebo and beta-carotene , respectively , but only by 14 % ( 95 % CI : -33 to 93 % ) among those receiving vitamin A. Thus , 6-mo mortality was higher among infants of women who had night blindness during pregnancy . Maternal receipt of vitamin A reduced this risk Vitamin A supplementation reduces mortality in young children in areas of endemic vitamin A deficiency . However , it has no impact on the incidence of common morbidities . This discrepancy has been explained by an impact on case fatality , although with the exception of hospitalized measles cases , there is little direct evidence to support this hypothesis . We assessed the impact of newborn dosing with vitamin A on the incidence and case fatality of common childhood morbidities in early infancy in a community-based , r and omized trial in South India . Morbidity for each day in the previous 2 wk was assessed for the first 6 mo of life . A total of 11,619 live-born infants were enrolled and r and omized to receive either 48,000 IU ( 50.4 micromol retinol ) of oral vitamin A or placebo following delivery . There was no difference between treatment groups in the incidence of acute or chronic diarrhea , dysentery , or fever but a small increased incidence of acute respiratory illness ( ARI ) . Case fatality for diarrhea and fever were significantly reduced in the vitamin A group compared with placebo ( relative case fatality [ 95 % CI ] of 0.50 [ 0.27 , 0.90 ] and 0.60 [ 0.40 , 0.88 ] , respectively ) . There was a trend in reduction of case fatality for various definitions of ARI , but the evidence for this effect was modest . Survival analysis among those with morbid episodes confirmed the case fatality analysis . This trial demonstrated that the reduction in overall mortality due to newborn vitamin A dosing was driven primarily by a reduction in case fatality among infants OBJECTIVE To reduce prevalence of anaemia in low-income postpartum women . DESIGN A r and omised , non-blind clinical trial was conducted among 959 low-income , postpartum women in eleven clinics in Mississippi . The clinics were r and omised to one of three treatment groups : ( i ) selective anaemia screening of high-risk women as recommended currently ( control ) ; ( ii ) universal anaemia screening and treatment of anaemic women ( group I ) ; and ( iii ) universal Fe supplementation of 65 mg/d for two months to all low-income women ( group II ) . All study participants within each clinic received the same treatment . Women were followed up at 6 months after delivery . Hb was measured at baseline and at follow-up . The primary outcome variable was the proportion of women with anaemia after treatment . SETTING Eleven health clinics in Mississippi . SUBJECTS Low-income , postpartum women . RESULTS Baseline characteristics of the three study groups were compared using one-way ANOVA and an appropriate post hoc test for continuous variables and the χ2 test for categorical variables . Fifty-two per cent of postpartum women were anaemic ( Hb < 12·0 g/dl ) and the rate decreased to 33 % at 6 months after the intervention . Group II women , who received universal Fe supplementation , improved their Hb status significantly ( P < 0·001 ) at 6 months postpartum compared with the other groups . Prevalence of anaemia was also significantly lower among group II women ( 22·5 % ) compared with controls ( 34 % ) and group I women ( 43 % ; P < 0·001 ) . CONCLUSIONS A universal Fe supplementation strategy was effective in reducing the prevalence of anaemia among low-income postpartum women Background Maternal mortality is a major health problem concentrated in re source -poor regions . Accurate data on its causes using rigorous methods is lacking , but is essential to guide policy-makers and health professionals to reduce this intolerable burden . The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction , in one of the regions of the world with the highest maternal mortality ratios . Methods and Findings We conducted a prospect i ve study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo , Mozambique , using complete autopsies with histological examination . HIV detection was done by virologic and serologic tests , and malaria was diagnosed by histological and parasitological examination . During 26 mo there were 179 maternal deaths , of which 139 ( 77.6 % ) had a complete autopsy and formed the basis of this analysis . Of those with test results , 65 women ( 52.8 % ) were HIV-positive . Obstetric complications accounted for 38.2 % of deaths ; haemorrhage was the most frequent cause ( 16.6 % ) . Nonobstetric conditions accounted for 56.1 % of deaths ; HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis were the most common causes ( 12.9 % , 12.2 % , 10.1 % and 7.2 % respectively ) . Mycobacterial infection was found in 12 ( 8.6 % ) maternal deaths . Conclusions In this tertiary hospital in Mozambique , infectious diseases accounted for at least half of all maternal deaths , even though effective treatment is available for the four leading causes , HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis . These observations highlight the need to implement effective and available prevention tools , such as intermittent preventive treatment and insecticide-treated bed-nets for malaria , antiretroviral drugs for HIV/AIDS , or vaccines and effective antibiotics for pneumococcal and meningococcal diseases . Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement BACKGROUND Prenatal supplementation with micronutrients may increase birth weight and thus improve infant health and survival in setting s where infants and children are at risk of micronutrient deficiencies . OBJECTIVE To assess whether vitamin A and /or zinc supplementation given during pregnancy can improve birth weight , birth length , neonatal morbidity , or infant mortality . METHODS A double-blind , r and omized controlled trial supplementing women ( n = 2173 ) in Central Java , Indonesia throughout pregnancy with vitamin A , zinc , combined vitamin A+zinc , or placebo . RESULTS Out of 2173 supplemented pregnant women , 1956 neonates could be evaluated . Overall , zinc supplementation improved birth length compared to placebo or combined vitamin A+zinc ( 48.8 vs. 48.5 cm , p = 0.04 ) ; vitamin A supplementation improved birth length compared to placebo or combined vitamin A+zinc ( 48.7 vs. 48.2 cm , p = 0.04 ) . These effects remained after adjusting for maternal height , pre-pregnancy weight , and parity . There was no effect of supplementation on birth weight , the proportion of low birth weight , neonatal morbidity , or mortality . CONCLUSIONS Prenatal zinc or vitamin A supplementation demonstrates a small but significant effect on birth length , but supplementation with zinc , vitamin A or a combination of zinc and vitamin A , have no effect on birth weight , neonatal morbidity , or mortality This study tested the hypothesis that individual counselling in the third trimester would increase postpartum contraceptive use to a greater extent than only providing an educational leaflet . A total of 180 third trimester pregnant women of mean age 28.3 years who were attending Marmara University Hospital for prenatal care were enrolled . One-third were r and omly allocated to receive prenatal contraceptive counselling and the remaining two-thirds ( control group ) received an educational leaflet . Participants were followed-up at 6–9 months postpartum . The majority of subjects ( 91.5 % ) wanted to use contraception after delivery but 26.7 % did not know which method to use . At follow-up , 79.6 % of all women had begun a postpartum contraceptive regime and 68.7 % were using a modern contraceptive method . Overall , there was no statistically significant difference in postpartum contraception use between the control and intervention groups in this study population . It is , therefore , concluded that prenatal counselling was not superior to educational leaflets for increasing the use of effective and modern postpartum contraception OBJECTIVE To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A , either preformed or as beta carotene . DESIGN Double blind , cluster r and omised , placebo controlled field trial . SETTING Rural southeast central plains of Nepal ( Sarlahi district ) . SUBJECTS 44 646 married women , of whom 20 119 became pregnant 22 189 times . INTERVENTION 270 wards r and omised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo , vitamin A ( 7000 micrograms retinol equivalents ) or beta carotene ( 42 mg , or 7000 micrograms retinol equivalents ) for over 31/2 years . MAIN OUTCOME MEASURES All cause mortality in women during pregnancy up to 12 weeks post partum ( pregnancy related mortality ) and mortality during pregnancy to 6 weeks postpartum , excluding deaths apparently related to injury ( maternal mortality ) . RESULTS Mortality related to pregnancy in the placebo , vitamin A , and beta carotene groups was 704 , 426 , and 361 deaths per 100 000 pregnancies , yielding relative risks ( 95 % confidence intervals ) of 0 . 60 ( 0.37 to 0.97 ) and 0.51 ( 0.30 to 0.86 ) . This represented reductions of 40 % ( P<0.04 ) and 49 % ( P<0.01 ) among those who received vitamin A and beta carotene . Combined , vitamin A or beta carotene lowered mortality by 44 % ( 0.56 ( 0.37 to 0.84 ) , P<0.005 ) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births , or by 40 % ( P<0.02 ) . Differences in cause of death could not be reliably distinguished between supplemented and placebo groups . CONCLUSION Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural , undernourished population s of south Asia The practice and timing of routine antenatal visits for healthy pregnant women , introduced arbitrarily and without evidence of effectiveness , have become entrenched in obstetric practice over the last century . In 2001 the large , cluster r and omized WHO Antenatal Care Trial concluded that a goal -orientated package of antenatal care with reduced visits seemed not to affect maternal and perinatal outcomes . The reduced visit package has been implemented in several countries . The current re- analysis finds that the significantly increased perinatal mortality which occurred in the reduced visit package persists after adjustment for potential confounding factors . The WHO Antenatal Care Trial provided the first evidence from a r and omized trial that the traditional high frequency of routine visits in the third trimester may well reduce perinatal mortality BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development BACKGROUND Postpartum haemorrhage is a leading cause of maternal morbidity and mortality . Active management of the third stage of labour , including use of a uterotonic agent , has been shown to reduce blood loss . Misoprostol ( a prostagl and in E1 analogue ) has been suggested for this purpose because it has strong uterotonic effects , can be given orally , is inexpensive , and does not need refrigeration for storage . We did a multicentre , double-blind , r and omised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour . METHODS In hospitals in Argentina , China , Egypt , Irel and , Nigeria , South Africa , Switzerl and , Thail and , and Vietnam , we r and omly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly , according to routine practice , plus corresponding identical placebos . The medications were administered immediately after delivery as part of the active management of the third stage of labour . The primary outcomes were measured postpartum blood loss of 1000 mL or more , and the use of additional uterotonics without an unacceptable level of side-effects . We chose an upper limit of a 35 % increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence , which was assessed by the confidence interval of the relative risk . Analysis was by intention to treat . FINDINGS 9264 women were assigned misoprostol and 9266 oxytocin . 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded . 366 ( 4 % ) of women on misoprostol had a measured blood loss of 1000 mL or more , compared with 263 ( 3 % ) of those on oxytocin ( relative risk 1.39 [ 95 % CI 1.19 - 1.63 ] , p<0.0001 ) . 1398 ( 15 % ) women in the misoprostol group and 1002 ( 11 % ) in the oxytocin group required additional uterotonics ( 1.40 [ 1.29 - 1.51 ] , p<0.0001 ) . Misoprostol use was also associated with a significantly higher incidence of shivering ( 3.48 [ 3.15 - 3.84 ] ) and raised body temperature ( 7.17 [ 5.67 - 9.07 ] ) in the first hour after delivery . INTERPRETATION 10 IU oxytocin ( intravenous or intramuscular ) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital setting s where active management is the norm BACKGROUND Results of r and omised controlled trials of newborn ( age 1 - 3 days ) vitamin A supplementation have been inconclusive . The WHO is coordinating three large r and omised trials in Ghana , India , and Tanzania ( Neovita trials ) . We present the findings of the Neovita trial in Ghana . METHODS This study was a population -based , individually r and omised , double-blind , placebo-controlled trial in the Brong Ahafo region of Ghana . The trial participants were infants aged at least 2 h , identified at home or facilities on the day of birth or in the next 2 days , able to feed orally , and likely to stay in the study area for at least 6 months . They were r and omly assigned ( ratio 1:1 ) to receive either one oral dose of vitamin A ( 50,000 IU ) or placebo immediately after recruitment . The research team and parents of the infants were masked to treatment assignment . Follow-up home visits were undertaken every 4 weeks , when data were recorded for deaths , facility use , and care seeking . The primary outcome was post-supplementation mortality to 6 months of age . Analysis was by intention to treat . Potential adverse events were recorded at 1 and 3 days after supplementation . This trial is registered with the Australian New Zeal and Clinical Trials Registry (ANZCTR)CTRN12610000582055 . FINDINGS We assessed 26,414 livebirths for eligibility between Aug 16 , 2010 , and Nov 7 , 2011 . We recruited 22,955 newborn infants , with 11,474 r and omly assigned to receive vitamin A and 11,481 to receive placebo . Loss to follow-up was low with vital status at 6 months of age reported for 22,698 ( 98·9 % ) infants . We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group ( mortality risk 24·5 in 1000 supplemented infants ) and 248 deaths in the placebo group ( mortality risk 21·8 per 1000 supplemented infants ) , relative risk ( RR ) 1·12 ( 95 % CI 0·95 - 1·33 ; p=0·183 ) and risk difference ( RD ) 2·66 ( 95 % CI -1·25 to 6·57 ; p=0·18 ) . Adverse events within 3 days of supplementation did not differ by trial group . 122 infants died in the first 3 days after supplementation ; 70 ( 0·6 % ) in the vitamin A and 52 ( 0·5 % ) in the placebo group ( risk ratio [ RR ] 1·35 , 95 % CI 0·94 - 1·93 , p=0·102 ) . 53 infants were reported to have a bulging fontanelle ; 32 ( 0·3 % ) in the vitamin A group and 21 ( 0·2 % ) in the placebo group ( RR 1·53 , 0·88 - 2·62 , p=0·130 ) . INTERPRETATION The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana . FUNDING Bill & Melinda Gates Foundation grant to the WHO Please cite this paper as : Mobeen N , Durocher J , Zuberi N , Jahan N , Blum J , Wasim S , Walraven G , Hatcher J. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan : a r and omised placebo‐controlled trial . BJOG 2011;118:353–361 OBJECTIVES New developments in proteinuria assessment have included the use of spot urinary microalbumin to creatinine ratio measurements . This study determines the accuracy of spot urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks compared to the 24h urinary protein ( gold st and ard ) to detect significant proteinuria in hypertensive pregnant women . STUDY DESIGN 163 women presenting with pregnancy hypertension were recruited from antenatal clinics . On admission each participant had a spot urine sample tested using a semi-quantitative visual dipstick and a spot midstream urine sample collected and analysed using the semi-quantitative urinary microalbumin to creatinine ratio dipsticks read instrumentally on the Clinitek 50 urine chemistry analyser . A 24 h urinary protein estimation was then performed . The results of the urinary microalbumin to creatinine ratio dipsticks and the conventional visual dipsticks were compared to the 24 h urine protein . A urinary microalbumin to creatinine ratio of > or = 300 mg/g ( 1 + to 4 + on urine dipsticks ) was considered a positive result > or = 0.3g/24 h was considered significant proteinuria . RESULTS The visual dipstick had a sensitivity of 51 % ( 95 % CI [ 0.41 - 0.61 ] ) and specificity of 91 % ( 95 % CI [ 0.81 - 0.96 ] ) . The PPV and NPV was 89 % ( 95 % CI [ 0.77 - 0.95 ] ) and 58 % ( 95 % CI [ 0.48 - 0.67 ] ) , respectively . The urinary microalbumin to creatinine ratio dipsticks had a sensitivity of 63 % ( 95 % CI [ 0.52 - 0.72 ] ) and specificity of 81 % ( 95 % CI [ 0.70 - 0.89 ] ) . The PPV was 82 % ( 95 % CI [ 0.71 - 0.90 ] ) and NPV was 62 % ( 95 % CI [ 0.51 - 0.71 ] ) . CONCLUSION Neither the visual dipstick nor the urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system is accurate when compared to the total 24h urinary protein . Differences between the urinary microalbumin to creatinine ratio and 24h total urinary protein may be due to the variation in the albumin fraction of the total urinary protein of pre-eclampsia , technical problems with imprecision of the assay technique , and clinical causes of false positives and negatives . The improved sensitivity of the automated urinary microalbumin to creatinine ratio dipstick over the visual dipstick suggests it may be a suitable substitute for the visual dipstick in clinical practice IMPORTANCE Anemia is common in pregnancy and increases the risk of adverse outcomes . Iron deficiency is a leading cause of anemia in sub-Saharan Africa , and iron supplementation is the st and ard of care during pregnancy ; however , recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions . There is limited evidence on the safety of iron supplementation during pregnancy in these areas . OBJECTIVE To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized , double-blind , placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam , Tanzania , from September 28 , 2010 , through October 4 , 2012 . Iron-replete , nonanemic women were eligible if they were uninfected with human immunodeficiency virus , primigravidae or secundigravidae , and at or before 27 weeks of gestation . Screening of 21,316 women continued until the target enrollment of 1500 was reached . Analyses followed the intent-to-treat principle and included all r and omized participants . INTERVENTIONS Participants were r and omized to receive 60 mg of iron or placebo , returning every 4 weeks for st and ard prenatal care , including malaria screening , prophylaxis with the combination of sulfadoxine and pyrimethamine , and treatment , as needed . MAIN OUTCOMES AND MEASURES The primary outcomes were placental malaria , maternal hemoglobin level at delivery , and birth weight . RESULTS Among 1500 study participants ( 750 r and omized for each group ) , 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental sample s included in the analysis . Maternal characteristics were similar at baseline in the iron and placebo groups , and 1354 ( 91.7 % ) used malaria control measures . The risk of placental malaria was not increased by maternal iron supplementation ( relative risk [ RR ] , 1.03 ; 95 % CI , 0.65 - 1.65 ) , and iron supplementation did not significantly affect birth weight ( 3155 vs 3137 g , P = .89 ) . Compared with placebo , iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin ( 0.1 vs -0.7 g/dL , P < .001 ) and serum ferritin ( 41.3 vs 11.3 µg/L , P < .001 ) . Iron supplementation significantly decreased the risk of anemia at delivery by 40 % ( RR , 0.60 ; 95 % CI , 0.51 - 0.71 ) but not severe anemia ( RR , 0.68 ; 95 % CI , 0.41 - 1.14 ) . Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52 % ( RR , 0.48 ; 95 % CI , 0.32 - 0.70 ) and the risk of iron deficiency anemia by 66 % ( RR , 0.34 ; 95 % CI , 0.19 - 0.62 ) . CONCLUSIONS AND RELEVANCE Prenatal iron supplementation among iron-replete , nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control . Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group . These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01119612 BACKGROUND Neonatal tetanus is the cause of 23 to 73 % of neonatal deaths in developing countries and continues to be an important killer in many parts of India . METHODS In this nonr and omized cohort study in a rural area in India , tetanus toxoid immunization status was recorded for 1688 pregnant women . Liveborn children were followed up for 30 days for the occurrence of neonatal tetanus . Nonimmunized and partially immunized women were asked their reasons for not receiving tetanus toxoid vaccine . RESULTS Complete prenatal immunization with tetanus toxoid during pregnancy ( two doses 1 month apart ) was associated with an 88 % reduction in the risk of neonatal tetanus among the newborn children [ 95 % confidence interval ( CI ) 59 to 98 % ] . In multivariable analysis only complete immunization and the use of clean instruments for cutting the umbilical cord were independently associated with a reduction in risk of neonatal tetanus . Registration by the health care provider before 29 weeks of gestation , being 5 km or less from the vaccination facility , having two or more contacts with the health provider and having some school education were independently associated with complete immunization . CONCLUSIONS Immunization of pregnant women with tetanus toxoid was the single most effective intervention against neonatal tetanus independent of other interventions OBJECTIVE : To test the effectiveness of cognitive-behavioral counseling on the rate and duration of exclusive breastfeeding ( EBF ) during the first 6 months of an infant ’s life compared with routine counseling . METHODS : A single blind cluster-r and omized controlled trial was undertaken in 40 Union Councils of a rural district in the northwest province of Pakistan between May 2009 and April 2010 . By simple unmatched r and omization , 20 Union Councils were each allocated to intervention and control arms . Two hundred twenty-four third trimester pregnant women in the intervention and 228 third trimester pregnant women in the control arm were enrolled and followed-up biweekly until 6 months postpartum . Analyses were by intention to treat . Mothers in the intervention group received 7 sessions of cognitive-behavioral counseling from antenatal to 6 months postpartum , whereas the control group received an equal number of routine sessions . Proportion of mothers exclusively breastfeeding at 6 months postpartum and duration of EBF through these 6 months was assessed . RESULTS : At 6 months postpartum , 59.6 % of mothers in the intervention arm and 28.6 % in the control arm were exclusively breastfeeding . This translates into a 60 % reduced risk of stopping exclusively breastfeeding during the first 6 months ( adjusted hazard ratio , 0.40 [ 95 % confidence interval : 0.27–0.60 ] , P < .001 ) . Mothers in the intervention group were half as likely to use prelacteal feeds with their infants ( adjusted relative risk , 0.51 [ 95 % confidence interval : 0.34–0.78 ] ) . CONCLUSIONS : Compared with routine counseling , cognitive-behavioral counseling significantly prolonged the duration of EBF , doubling the rates of EBF at 6 months postpartum BACKGROUND Omphalitis contributes to neonatal morbidity and mortality in developing countries . Umbilical cord cleansing with antiseptics might reduce infection and mortality risk , but has not been rigorously investigated . METHODS In our community-based , cluster-r and omised trial , 413 communities in Sarlahi , Nepal , were r and omly assigned to one of three cord-care regimens . 4934 infants were assigned to 4.0 % chlorhexidine , 5107 to cleansing with soap and water , and 5082 to dry cord care . In intervention clusters , the newborn cord was cleansed in the home on days 1 - 4 , 6 , 8 , and 10 . In all clusters , the cord was examined for signs of infection ( pus , redness , or swelling ) on these visits and in follow-up visits on days 12 , 14 , 21 , and 28 . Incidence of omphalitis was defined under three sign-based algorithms , with increasing severity . Infant vital status was recorded for 28 completed days . The primary outcomes were incidence of neonatal omphalitis and neonatal mortality . Analysis was by intention-to-treat . This trial is registered with , number NCT00109616 . FINDINGS Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group . Severe omphalitis in chlorhexidine clusters was reduced by 75 % ( incidence rate ratio 0.25 , 95 % CI 0.12 - 0.53 ; 13 infections/4839 neonatal periods ) compared with dry cord-care clusters ( 52/4930 ) . Neonatal mortality was 24 % lower in the chlorhexidine group ( relative risk 0.76 [ 95 % CI 0.55 - 1.04 ] ) than in the dry cord care group . In infants enrolled within the first 24 h , mortality was significantly reduced by 34 % in the chlorhexidine group ( 0.66 [ 0.46 - 0.95 ] ) . Soap and water did not reduce infection or mortality risk . INTERPRETATION Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation Background There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations ( MMS ) on their offspring 's growth . We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth . The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0 - 54 months and a combination of these interventions would further improve these outcomes . Methods In the large , r and omized MINIMat trial ( Maternal and Infant Nutrition Interventions in Matlab ) , Bangladesh , 4436 pregnant women were enrolled between November 2001 and October 2003 and their children were followed until March 2009 . Participants were r and omized into six groups comprising 30 mg Fe and 400 μg folic acid ( Fe30F ) , 60 mg Fe and 400 μg folic acid ( Fe60F ) or MMS combined with either an early ( immediately after identification of pregnancy ) or a later usual ( at the time of their choosing , i.e. , usual care in this community ) program invitation to food supplementation . The anthropometry of 3267 children was followed from birth to 54 months , and 2735 children were available for analysis at 54 months . Results There were no differences in characteristics of mothers and households among the different intervention groups . The average birth weight was 2694 g and birth length was 47.7 cm , with no difference among intervention groups . Early invitation to food supplementation ( in comparison with usual invitation ) reduced the proportion of stunting from early infancy up to 54 months for boys ( p = 0.01 ) , but not for girls ( p = 0.31 ) . MMS result ed in more stunting than st and ard Fe60F ( p = 0.02 ) . There was no interaction between the food and micronutrient supplementation on the growth outcome . Conclusions Early food supplementation in pregnancy reduced the occurrence of stunting during 0 - 54 months in boys , but not in girls , and prenatal MMS increased the proportion of stunting in boys . These effects on postnatal growth suggest programming effects in early fetal life . Trial registration numberIS RCT N : IS RCT A study was carried out in Misungwi and Kwimba Districts , Tanzania to determine the effectiveness of clean delivery kits in preventing cord infection and puerperal sepsis and to provide qualitative information on community acceptability , correct use , and appropriateness of the kits . This study involved pregnant women aged 18 - 45 years old . In the delivery kit intervention population , the Maternal and Child Health Aide ( MCHA ) assigned to the health facility provided pregnant mothers with a clean delivery kit on their first antenatal visit . She explained how to use each of the kit components , with the aid of pictorial instructions included in the kit . The pregnant mothers were asked to convey the information to whoever assisted them during delivery . The MCHA also gave them health education based on the principles of the " six cleans " recognized by WHO ( i.e. , clean h and s , clean perineum , clean delivery surface , clean cord cutting and tying instruments , clean cutting surface ) . Women received the clean delivery kit free of charge in accordance with the r and omised stepped-wedge design schedule . During the first week following delivery , the Village Health Workers ( VHWs ) from both the intervention and control groups made two visits to the households of mothers who had delivered . They administered question naire about delivery to mother and birth attendant . During the two scheduled postpartum visits , those who were suspected to have puerperal sepsis or cord infection of the baby were referred to the health facility clinician for confirmation . Results indicated that use of clean delivery kit had a positive effect on reducing both cord infection and puerperal sepsis . The use of a clean home delivery kit coupled with an educational intervention about the " six cleans " had a significant effect on reducing the incidence of cord infection and puerperal sepsis among women enrolled in the study . In low re source setting s where home birth is common and clean delivery supplies are scarce , disposable kits can be made available through health clinics , markets , pharmacies or other channels to help reduce rates of infection OBJECTIVE . We adapted kangaroo mother care for immediate postnatal community-based application in rural Bangladesh , where the incidence of home delivery , low birth weight , and neonatal and infant mortality is high and neonatal intensive care is unavailable . This trial tested whether community-based kangaroo mother care reduces the overall neonatal mortality rate by 27.5 % , infant mortality rate by 25 % , and low birth weight neonatal mortality rate by 30 % . METHODS . Half of 42 unions in 2 Bangladesh divisions with the highest infant mortality rates were r and omly assigned to community-based kangaroo mother care , and half were not . One village per union was r and omly selected proportionate to union population size . A baseline survey of 39888 eligible consenting women collected sociodemographic information . Community-based workers were taught to teach community-based kangaroo mother care to all expectant and postpartum women in the intervention villages . A total of 4165 live births were identified and enrolled . Newborns were followed for 30 to 45 days and infants were followed quarterly through their first birthday to record infant care , feeding , growth , health , and vital status . RESULTS . Forty percent overall and ∼65 % of newborns who died were not weighed at birth , and missing birth weight was differential by study group . There was no difference in overall neonatal mortality rate or infant mortality rate . Except for care seeking , community-based kangaroo mother care behaviors were more common in the intervention than control group , but implementation was weak compared with the pilot study . CONCLUSIONS . The extensive missing birth weight and its potential bias render the evidence insufficient to justify implementing community-based kangaroo mother care . Additional experimental research ensuring baseline comparability of mortality , adequate kangaroo mother care implementation , and birth weight assessment is necessary to clarify the effect of community-based kangaroo mother care on survival BACKGROUND In HIV-1-infected women , poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes . We assessed the effects of vitamin A and multivitamins on birth outcomes in such women . METHODS In Tanzania , 1075 HIV-1-infected pregnant women at between 12 and 27 weeks ' gestation received placebo ( n=267 ) , vitamin A ( n=269 ) , multivitamins excluding vitamin A ( n=269 ) , or multivitamins including vitamin A ( n=270 ) in a r and omised , double-blind , placebo-controlled trial with a 2x2 factorial design . We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets . We did analyses by intention to treat . RESULTS 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins ( relative risk 0.61 [ 95 % CI 0.39 - 0.94 ] p=0.02 ) . Multivitamin supplementation decreased the risk of low birthweight ( < 2500 g ) by 44 % ( 0.56 [ 0.38 - 0.82 ] p=0.003 ) , severe preterm birth ( < 34 weeks of gestation ) by 39 % ( 0.61 [ 0.38 - 0.96 ] p=0.03 ) , and small size for gestational age at birth by 43 % ( 0.57 [ 0.39 - 0.82 ] p=0.002 ) . Vitamin A supplementation had no significant effect on these variables . Multivitamins , but not vitamin A , result ed in a significant increase in CD4 , CD8 , and CD3 counts . INTERPRETATION Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women . The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained BACKGROUND Supplementation of vitamin A in children aged 6 - 59 months improves child survival and is implemented as global policy . Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results . We aim ed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days ( 6 months ) . METHODS We did an individually r and omised , double-blind , placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania . Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam . In Kilombero , Ulanga , and Kilosa districts , women were seen at home as part of the health and demographic surveillance system . Newborn infants were eligible for r and omisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months . We r and omly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth . Infants were r and omly assigned in blocks of 20 , and investigators , participants ' families , and data analysis teams were masked to treatment assignment . We assessed infants on day 1 and day 3 after dosing , as well as at 1 , 3 , 6 , and 12 months after birth . The primary endpoint was mortality at 6 months , assessed by field interviews . The primary analysis included only children who were not lost to follow-up . This trial is registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12610000636055 . FINDINGS Between Aug 26 , 2010 , and March 3 , 2013 , 31,999 newborn babies were r and omly assigned to receive vitamin A ( n=15,995 ) or placebo ( n=16,004 ; 15,428 and 15,464 included in analysis of mortality at 6 months , respectively ) . We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months ( 26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group ; risk ratio 1·10 , 95 % CI 0·95 - 1·26 ; p=0·193 ) . There was no evidence of a differential effect for vitamin A supplementation on mortality by sex ; risk ratio for mortality at 6 months for boys was 1·08 ( 0·90 - 1·29 ) and for girls was 1·12 ( 0·91 - 1·39 ) . There was also no evidence of adverse effects of supplementation within 3 days of dosing . INTERPRETATION Neonatal vitamin A supplementation did not result in any immediate adverse events , but had no beneficial effect on survival in infants in Tanzania . These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation . FUNDING Bill & Melinda Gates Foundation to WHO Aim : To eluci date the impact of bathing on the prevalence of hypothermia among newborn babies exposed to the skin‐to‐skin ( STS ) care technique before and after bathing . Methods : Non‐asphyxiated newborns after vaginal delivery ( n=249 ) in a Ug and an referral hospital were consecutively enrolled and r and omized either to bathing at 60 min postpartum ( n=126 ) or no bathing ( n=123 ) . All mothers practised skin‐to‐skin care of their newborns . Four rectal and tympanic registration s of newborn temperatures were carried out in both groups directly after drying at birth , and at 60 , 70 and 90 min postpartum . Results : Bathing of newborns in the first hour after delivery result ed in a significantly increased prevalence of hypothermia , defined as temperature < 36.5 ° C , at 70 and at 90 min postpartum despite the use of warmed water and the application of the STS method . There was no neonatal mortality . Aside from the bathing procedure , no background factor potentially predisposing the newborns to hypothermia was identified Aim : Conventional care of prematurely born infants involves extended maternal‐infant separation and incubator care . Recent research has shown that separation causes adverse effects . Maternal‐infant skin‐to‐skin contact ( SSC ) provides an alternative habitat to the incubator , with proven benefits for stable prematures ; this has not been established for unstable or newborn low‐birthweight infants . SSC from birth was therefore compared to incubator care for infants between 1200 and 2199 g at birth . Methods : This was a prospect i ve , unblinded , r and omized controlled clinical trial ; potential subjects were identified before delivery and r and omized by computerized minimization technique at 5 min if eligible . St and ardized care and observations were maintained for 6 h. Stability was measured in terms of a set of pre‐determined physiological parameters , and a composite cardio‐respiratory stabilization score ( SCRIP ) . Results : 34 infants were analysed in comparable groups : 3/18 SSC compared to 12/13 incubator babies exceeded the pre‐determined parameters ( p < 0.001 ) . Stabilization scores were 77.11 for SSC versus 74.23 for incubator ( maximum 78 ) , mean difference 2.88 ( 95 % CI : 0.3–5.46 , p = 0.031 ) . All 18 SSC subjects were stable in the sixth hour , compared to 6/13 incubator infants . Eight out of 13 incubator subjects experienced hypothermia IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation Abstract Objective To assess the impact of supplementing newborn infants with vitamin A on mortality at age 6 months . Design Community based , r and omised , double blind , placebo controlled trial . Setting Two rural districts of Tamil Nadu , southern India . Participants 11 619 newborn infants allocated 24 000 IU oral vitamin A or placebo on days 1 and 2 after delivery . Main outcome measure Primary outcome measure was mortality at age 6 months . Results Infants in the vitamin A group had a 22 % reduction in total mortality ( 95%confidence interval 4 % to 37 % ) compared with those in the placebo group . Vitamin A had an impact on mortality between two weeks and three months after treatment , with no additional impact after three months . Conclusion Supplementing newborn infants with vitamin A can significantly reduce early infant mortality The long-term benefits of antenatal iron supplementation in child survival are not known . In 1999 - 2001 , 4,926 pregnant women in rural Nepal participated in a cluster-r and omized , double-masked , controlled trial involving 4 alternative combinations of micronutrient supplements , each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls , who received vitamin A only . They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival . Of 4,130 livebirths , 209 infants died in the first 3 months and 8 were lost to follow-up . Of those remaining , 3,761 were followed , 150 died between ages 3 months and 7 years , and 152 were lost to follow-up . Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group , as follows : folic acid , 13.4 ; folic acid-iron , 10.3 ; folic acid-iron-zinc , 12.0 ; multiple micronutrients ; 14.0 ; and controls , 15.2 . Hazard ratios were 0.90 ( 95 % confidence interval ( CI ) : 0.65 , 1.22 ) , 0.69 ( 95 % CI : 0.49 , 0.99 ) , 0.80 ( 95 % CI : 0.58 , 1.11 ) , and 0.93 ( 95 % CI : 0.66 , 1.31 ) , respectively , in the 4 supplementation groups . Maternal iron-folic acid supplementation reduced mortality among these children by 31 % between birth and age 7 years . These results provide additional motivation for strengthening antenatal iron-folic acid programs Aims : Evidence exists about prevention of postpartum haemorrhage ( PPH ) by oral administration of misoprostol in low-income countries , but effectiveness of prevention by lay community health workers ( CHW ) is not sufficient . This study aim ed to investigate whether a single dose ( 400 µg ) of oral misoprostol could prevent PPH in a community home-birth setting and to assess its acceptability and feasibility among rural Bangladeshi women . Methods : This quasi-experimental trial was conducted among 2,017 rural women who had home deliveries between November 2009 and February 2010 in two rural districts of northern Bangladesh . In the intervention district 1,009 women received 400 µg of misoprostol immediately after giving birth by the lay CHWs , and in the control district 1,008 women were followed after giving birth with no specific intervention against PPH . Primary PPH ( within 24 hours ) was measured by women 's self-reported subjective measures of the normality of blood loss using the ‘ cultural consensus model . ’ Baseline data provided socio-economic , reproductive , obstetric , and bleeding disorder information . Findings : The incidence of primary PPH was found to be lower in the intervention group ( 1.6 % ) than the control group ( 6.2 % ) ( p<0.001 ) . Misoprostol provided 81 % protection ( RR : 0.19 ; 95 % CI : 0.08–0.48 ) against developing primary PPH . The proportion of retained and manually removed placentae was found to be higher in the control group compared to the intervention group . Women in the control group were more likely to need an emergency referral to a higher level facility and blood transfusion than the intervention group . Unexpectedly few women experienced transient side effects of misoprostol . Eighty-seven percent of the women were willing to use the drug in future pregnancy and would recommend to other pregnant women . Conclusion : Community-based distribution of oral misoprostol ( 400 µg ) by CHW appeared to be effective , safe , acceptable , and feasible in reducing the incidence of PPH in rural areas of Bangladesh . This strategy should be scaled up across the country where access to skilled attendance is limited Background Maternal diet during pregnancy is one of the most important factors associated with adequate fetal growth . There are many complications associated with fetal growth restriction that lead to lifelong effects . The aim of this review was to describe the studies examining the effects of protein energy supplementation during pregnancy on fetal growth focusing on the context ual differences . Methods Relevant articles published between 2007 and 2012 were identified through systematic electronic search es of the PubMed , Science Direct , and EBSCO data base and the examination of the bibliographies of retrieved articles . The search aim ed to identify studies examining pregnant women receiving protein and /or energy during pregnancy and to assess fetal growth measures . Data of effectiveness and practical aspects of protein energy supplementation during pregnancy were extracted and compiled . Results Twenty studies ( 11 r and omized controlled trials , 8 controlled before and after , and 1 prospect i ve study ) were included in this review . Positive outcomes in infants and women can not be expected if the supplementation is not needed . Therefore , it is essential to correctly select women who will benefit from dietary intervention programs during pregnancy . However , there is currently no consensus on the most effective method of identifying these women . The content of protein in the supplements considering total diet is also an important determinant of fetal growth . Balanced protein energy supplementation ( containing up to 20 % of energy as protein ) given to pregnant women with energy or protein deficit appears to improve fetal growth , increase birth weight ( by 95–324 g ) and height ( by 4.6–6.1 mm ) , and decrease the percentage of low birth weight ( by 6 % ) . Supplements with excess protein ( > 20 % of energy as protein ) provided to women with a diet already containing adequate protein may conversely impair fetal growth . There is also no consensus on the best time to start supplementation . Conclusions Strong quality studies examining adequate criteria to screen women who would benefit from supplementation , time to start supplementation , and type of supplements are warranted Vitamin A is essential for immunity and growth . A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia , low birth weight , growth failure , HIV transmission , and mortality . Women received daily doses of iron and folate , either alone or combined with vitamin A ( 3 mg retinol equivalent ) , from 18 - 28 weeks ' gestation until delivery . In the vitamin A and control groups , respectively , the mean ( + /-SE ) birth weights were 2895+/-31 g and 2805+/-32 g ( P=.05 ) , the proportions of low-birth-weight infants were 14.0 % and 21.1 % ( P=.03 ) , the proportions of anemic infants at 6 weeks postpartum were 23.4 % and 40.6 % ( P<.001 ) , and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6 % and 27.8 % ( P=.76 ) and 27.7 % and 32.8 % ( P=.21 ) . Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia , but it did not affect perinatal HIV transmission OBJECTIVE To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine-pyrimethamine ( IPTp-SP ) in primi- and secundigravidae in rural Burkina Faso . METHODS Data of 1441 women enrolled in a health centre r and omized trial and delivering a live-singleton between September 2004 and October 2006 were analysed at individual level . Prevalence of peripheral and placental parasitaemia , anaemia ( PCV < 33 % ) , low-birth weight ( < 2500 g ; LBW ) , mean packed cell volume ( PCV ) and birth weight were compared in relation to the number of directly observed SP doses . RESULTS Two or more doses of SP significantly reduced the risk of placental parasitaemia [ adjusted odds ratio ( AOR ) = 0.04 , 95%CI = 0.003 - 0.60 , P = 0.023 ] and anaemia at delivery ( AOR = 0.31 , 95%CI = 0.18 - 0.52 , P < 0.001 ) . IPTp was associated with reduced risk of LBW in primigravidae ( AOR = 0.11 , 95%CI = 0.07 - 0.17 , P < 0.001 ) but not secundigravidae ( AOR = 0.70 , 95%CI = 0.26 - 1.91 , P = 0.452 ) . For each increment in number of SP doses mean PCV increased by 1.0 % ( 95%CI = 0.4 - 1.7 , P = 0.005 ) at 32 weeks gestation , by 1.2 % ( 95%CI = 0.2 - 2.2 , P = 0.025 ) at delivery and mean birth weight by 220 g ( 95%CI = 134 - 306 P < 0.001 ) in primigravidae and by 102 g ( 95%CI = 55 - 148 , P = 0.001 ) in secundigravidae . CONCLUSION The risk of malaria infection was significantly reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso . The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW . Incomplete uptake of IPTp-SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions . This needs to be taken into account when evaluating interventions at community level Objective : Immediate Kangaroo Mother Care ( KMC ) , an intervention following childbirth whereby the newborn is placed skin-to-skin ( STS ) on mother 's chest to promote thermal regulation , breastfeeding and maternal-newborn bonding , is being taught in very low-income countries to improve newborn health and survival . Existing data are review ed to document the association between community-based KMC ( CKMC ) implementation and its potential benefits . Study Design : New analyses of the sole r and omized controlled study of CKMC in Bangladesh and others ' experiences with immediate KMC are presented . Result : Newborns held STS less than 7 h per day in the first 2 days of life do not experience substantially better health or survival than babies without being held STS . Conclusion : Most women who were taught CKMC hold their newborns STS , but do so in a token manner unlikely to improve health or survival . Serious challenges exist to provide effective training and postpartum support to achieve adequate STS practice s. These challenges must be overcome before scaling up OBJECTIVES The aim of r and omized trial was to evaluate the effectiveness of anti-smoking counseling in the population of pregnant women from the maternity centers in Lódź , central Pol and . MATERIAL S AND METHODS One hundred and forty nine current smokers and 56 spontaneous quitters were r and omized into the smoking cessation intervention and 144 current smokers and 37 spontaneous quitters were included in the control group . The intervention program covered four midwife visits during pregnancy and one after delivery . The control units received st and ard written information about the health risk from maternal smoking to the fetus . RESULTS The chance of quitting smoking by the women was significantly higher in the intervention group than in the control group ( OR = 2.5 ; 95 % CI 1.8 - 3.7 ) . The difference in the mean infant birthweight between the quitters and non-quitters was 203.8 g ( p = 0.01 ) in the intervention group and 198.2 g in the control group ( p = 0.08 ) . After controlling for socio-demographic characteristics that could affect the birthweight , the differences remained significant in the intervention group - 182.8 g ( p = 0.02 ) , whereas in the control group it was 92.4 g ( p = 0.4 ) . CONCLUSIONS The midwife-assisted smoking cessation intervention seems to be an effective tool to help pregnant smokers make a decision to quit smoking BACKGROUND There are approximately 4 million neonatal deaths and half a million maternal deaths worldwide each year . There is limited evidence from clinical trials to guide the development of effective maternity services in developing countries . METHODS We performed a cluster-r and omized , controlled trial involving seven subdistricts ( talukas ) of a rural district in Pakistan . In three talukas r and omly assigned to the intervention group , traditional birth attendants were trained and issued disposable delivery kits ; Lady Health Workers linked traditional birth attendants with established services and documented processes and outcomes ; and obstetrical teams provided outreach clinics for antenatal care . Women in the four control talukas received usual care . The primary outcome measures were perinatal and maternal mortality . RESULTS Of the estimated number of eligible women in the seven talukas , 10,114 ( 84.3 percent ) were recruited in the three intervention talukas , and 9443 ( 78.7 percent ) in the four control talukas . In the intervention group , 9184 women ( 90.8 percent ) received antenatal care by trained traditional birth attendants , 1634 women ( 16.2 percent ) were seen antenatally at least once by the obstetrical teams , and 8172 safe-delivery kits were used . As compared with the control talukas , the intervention talukas had a cluster-adjusted odds ratio for perinatal death of 0.70 ( 95 percent confidence interval , 0.59 to 0.82 ) and for maternal mortality of 0.74 ( 95 percent confidence interval , 0.45 to 1.23 ) . CONCLUSIONS Training traditional birth attendants and integrating them into an improved health care system were achievable and effective in reducing perinatal mortality . This model could result in large improvements in perinatal and maternal health in developing countries OBJECTIVE The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery . STUDY DESIGN R and omized placebo-controlled , double-blinded trial in nulliparous normotensive women from population s with dietary calcium < 600 mg/d . Women who were recruited before gestational week 20 received supplements ( 1.5 g calcium/d or placebo ) throughout pregnancy . Primary outcomes were preeclampsia and preterm delivery ; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates . RESULTS The groups comprised 8325 women who were assigned r and omly . Both groups had similar gestational ages , demographic characteristics , and blood pressure levels at entry . Compliance were both 85 % and follow-up losses ( calcium , 3.4 % ; placebo , 3.7 % ) . Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia ( 4.1 % vs 4.5 % ) that was evident by 35 weeks of gestation ( 1.2 % vs 2.8 % ; P = .04 ) . Eclampsia ( risk ratio , 0.68 : 95 % CI , 0.48 - 0.97 ) and severe gestational hypertension ( risk ratio , 0.71 ; 95 % CI , 0.61 - 0.82 ) were significantly lower in the calcium group . Overall , there was a reduction in the severe preeclamptic complications index ( risk ratio , 0.76 ; 95 % CI , 0.66 - 0.89 ; life-table analysis , log rank test ; P = .04 ) . The severe maternal morbidity and mortality index was also reduced in the supplementation group ( risk ratio , 0.80 ; 95 % CI , 0.70 - 0.91 ) . Preterm delivery ( the neonatal primary outcome ) and early preterm delivery tended to be reduced among women who were < or = 20 years of age ( risk ratio , 0.82 ; 95 % CI , 0.67 - 1.01 ; risk ratio , 0.64 ; 95 % CI , 0.42 - 0.98 , respectively ) . The neonatal mortality rate was lower ( risk ratio , 0.70 ; 95 % CI , 0.56 - 0.88 ) in the calcium group . CONCLUSION A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity , maternal morbidity , and neonatal mortality , albeit these were secondary outcomes BACKGROUND Low maternal serum retinol level is a risk factor for mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) . Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality . The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency ; neonatal dosing is under consideration . We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT , HIV-free survival , and mortality in HIV-exposed infants . METHODS A total of 14,110 mother-infant pairs were enrolled < or = 96 h after delivery , and both mother and infant , mother only , infant only , or neither received vitamin A supplementation in a r and omized , placebo-controlled trial with a 2 x 2 factorial design . All but 4 mothers initiated breast-feeding . A total of 4495 infants born to HIV-positive women were included in the present analysis . RESULTS Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months . However , the timing of infant HIV infection modified the effect that supplementation had on mortality . Vitamin A supplementation had no effect in infants who were polymerase chain reaction ( PCR ) positive [ corrected ] for HIV at baseline . In infants who were PCR negative at baseline and PCR positive at 6 weeks , neonatal supplementation reduced mortality by 28 % ( P=.01 ) , but maternal supplementation had no effect . In infants who were PCR negative at 6 weeks , all 3 vitamin A regimens were associated with ~2-fold higher mortality ( P < or = .05 ) . CONCLUSIONS Targeted vitamin A supplementation of HIV-positive children prolongs their survival . However , postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks . These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas Abstract Objective : To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system . Design : 5 year controlled trial of all pregnant women in 28 villages r and omised to daily supplementation with high energy groundnut biscuits ( 4.3MJ/day ) for about 20 weeks before delivery ( intervention ) or after delivery ( control ) . Setting : Rural Gambia . Subjects : Chronically undernourished women ( twin bearers excluded ) , yielding 2047 singleton live births and 35 stillbirths . Main outcome measures : Birth weight ; prevalence of low birth weight ( < 2500 g ) ; head circumference ; birth length ; gestational age ; prevalence of stillbirths ; neonatal and postneonatal mortality . Results : Supplementation increased weight gain in pregnancy and significantly increased birth weight , particularly during the nutritionally debilitating hungry season ( June to October ) . Weight gain increased by 201 g ( P<0.001 ) in the hungry season , by 94 g ( P<0.01 ) in the harvest season ( November to May ) , and by 136 g ( P<0.001 ) over the whole year . The odds ratio for low birthweight babies in supplemented women was 0.61 ( 95 % confidence interval 0.47 to 0.79 , P<0.001 ) . Head circumference was significantly increased ( P<0.01 ) , but by only 3.1 mm . Birth length and duration of gestation were not affected . Supplementation significantly reduced perinatal mortality : the odds ratio was 0.47 ( 0.23 to 0.99 , P<0.05 ) for stillbirths and 0.54 ( 0.35 to 0.85 , P<0.01 ) for all deaths in first week of life . Mortality after 7 days was unaffected . Conclusion : Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers . This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality . The intervention can be successfully delivered through a primary healthcare system . Key messages In developing countries chronic maternal undernutrition is a prime contributor to the birth of over 25 million low birthweight babies annually and to high rates of neonatal mortality . An absence of well design ed field trials has created uncertainty about the potential efficacy of maternal feeding programmes This large scale r and omised controlled trial shows that dietary supplementation in pregnancy can be highly effective in reducing the proportion of low birthweight babies and perinatal mortality Incorporating supplementary feeding into a rural primary healthcare system is feasible Late pregnancy is the period most amenable to BACKGROUND Postpartum haemorrhage is a major cause of maternal mortality in the developing world . Although effective methods for prevention and treatment of such haemorrhage exist -- such as the uterotonic drug oxytocin -- most are not feasible in re source -poor setting s where many births occur at home . We aim ed to investigate whether oral misoprostol , a potential alternative to oxytocin , could prevent postpartum haemorrhage in a community home-birth setting . METHODS In a placebo-controlled trial undertaken between September , 2002 , and December , 2005 , 1620 women in rural India were r and omised to receive oral misoprostol ( n=812 ) or placebo ( n=808 ) after delivery . 25 auxiliary nurse midwives undertook the deliveries , administered the study drug , and measured blood loss . The primary outcome was the incidence of acute postpartum haemorrhage ( defined as > or = 500 mL bleeding ) within 2 h of delivery . Analysis was by intention-to-treat . The trial was registered with the US clinical trials data base ( http://www . clinical trials.gov ) as number NCT00097123 . FINDINGS Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage ( 12.0 % to 6.4 % , p<0.0001 ; relative risk 0.53 [ 95 % CI 0.39 - 0.74 ] ) and acute severe postpartum haemorrhage ( 1.2 % to 0.2 % , p<0.0001 ; 0.20 [ 0.04 - 0.91 ] . One case of postpartum haemorrhage was prevented for every 18 women treated . Misoprostol was also associated with a decrease in mean postpartum blood loss ( 262.3 mL to 214.3 mL , p<0.0001 ) . Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group . Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control . INTERPRETATION Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss . The drug 's low cost , ease of administration , stability , and a positive safety profile make it a good option in re source -poor setting The benefits of initiating breastfeeding in the first hour of life and exclusively breastfeeding thereafter are well documented . However , little is known about how best to promote these practice s. In this study , we assess the impact of Buddhist nuns and wat ( pagoda ) grannies on optimal breastfeeding behaviours in rural Cambodia . We did so by interviewing r and omly selected mothers of infants less than 6 months of age . A total of 440 mothers in programme and control communities completed the baseline survey ( before programme start-up ) , and 467 mothers responded 1 year later . Mothers ' exposure to breastfeeding promotion activities was high . At follow-up , 76 % of mothers in programme communities indicated that nuns had advised them about breastfeeding , 73 % received a home visit and 72 % reported attending an educational session . At baseline , mothers in programme communities were 11 % more likely ( RR = 1.11 , CI : 0.74 - 1.68 ) than mothers in control communities to initiate breastfeeding in the first hour of life . At follow-up , they were 62 % more likely ( RR = 1.62 , CI : 1.30 - 2.01 ) to do so . Similarly , at baseline , mothers in programme communities were 54 % more likely ( RR = 1.54 , CI : 1.21 - 1.96 ) than mothers in control communities to breastfeed exclusively in the previous 24 h. At follow-up , they were 81 % more likely ( RR = 1.81 , CI : 1.49 - 2.21 ) to do so . Programme planners may consider using community-based volunteers as one strategy to improve breastfeeding practice s and child survival In response to the concept that a good postpartum program should begin prenatally , this study was design ed to determine whether the provision of expert contraceptive counseling during the antenatal period would have an impact on contraceptive uptake , patterns of contraceptive usage , and pregnancy rates during the first year after childbirth . Over 500 women attending antenatal clinics in each of three centers ( Edinburgh , Scotl and ; Shanghai , People 's Republic of China ; Cape Town , South Africa ) were r and omized to receive expert contraceptive advice ( participants , n = 771 ) or the st and ard advice routinely given in that setting ( controls , n = 866 ) . Follow-up was by postal or interviewer-administered question naires at 16 and 52 weeks after childbirth . There were no significant differences in the prevalence of contraceptive use at one year ( over 79 % in all centers ) between participants and controls . In Edinburgh , participants were more likely to undergo sterilization ( p < 0.01 ) than controls , otherwise there were no differences among Edinburgh , Shanghai , or Cape Town in either the methods of contraception chosen or in the methods used over time . Contraceptive counseling delivered antenatally appeared to have no impact on the pregnancy rate during the first year after childbirth . In Shanghai , over 11 % of women in both groups underwent termination of pregnancy in the year of follow-up . In conclusion , although women in all centers said they found the opportunity to discuss contraception antenatally was useful , it had very little effect on contraceptive use or on subsequent pregnancy rates Objective To assess the effectiveness of 600 μg oral misoprostol on postpartum haemorrhage ( PPH ) and postpartum anaemia in a low income country home birth situation BACKGROUND Helminth infections during pregnancy may be associated with adverse outcomes , including maternal anemia , low birth weight , and perinatal mortality . Deworming during pregnancy has therefore been strongly advocated , but its benefits have not been rigorously evaluated . METHODS In Entebbe , Ug and a , 2507 pregnant women were recruited to a r and omized , double-blind , placebo-controlled trial investigating albendazole and praziquantel in a 2 x 2 factorial design [ IS RCT N32849447 ] . Hematinics and sulphadoxine-pyrimethamine for presumptive treatment of malaria were provided routinely . Maternal and perinatal outcomes were recorded . Analyses were by intention to treat . RESULTS At enrollment , 68 % of women had helminths , 45 % had hookworm , 18 % had Schistosoma mansoni infection ; 40 % were anemic ( hemoglobin level , < 11.2 g/dL ) . At delivery , 35 % were anaemic ; there was no overall effect of albendazole ( odds ratio [ OR ] , 0.95 ; 95 % confidence interval [ CI ] , 0.79 - 1.15 ) or praziquantel ( OR , 1.00 ; 95 % CI , 0.83 - 1.21 ) on maternal anemia , but there was a suggestion of benefit of albendazole among women with moderate to heavy hookworm ( OR , 0.45 ; 95 % CI , 0.21 - 0.98 ; P=.15 for interaction ) . There was no effect of either anthelminthic treatment on mean birth weight ( difference in mean associated with albendazole : -0.00 kg ; 95 % CI , -0.05 to 0.04 kg ; difference in mean associated with praziquantel : -0.01 kg ; 95 % CI , -0.05 to 0.04 kg ) or on proportion of low birth weight . Anthelminthic use during pregnancy showed no effect on perinatal mortality or congenital anomalies . CONCLUSIONS In our study area , where helminth prevalence was high but infection intensity was low , there was no overall effect of anthelminthic use during pregnancy on maternal anemia , birth weight , perinatal mortality , or congenital anomalies . The possible benefit of albendazole against anemia in pregnant women with heavy hookworm infection warrants further investigation BACKGROUND Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality . The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established . We aim ed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age . METHODS We undertook an individually r and omised , double-blind , placebo-controlled trial in Haryana , India . We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana , India , aged 15 - 49 years , and screened every identified livebirth . Eligible participants were neonates whose parents consented to participate , were likely to stay in the study area until at least 6 months of age , and were able to feed orally at the time of enrolment . Participants were r and omly assigned to receive oral capsules containing vitamin A ( retinol palmitate 50,000 IU plus vitamin E 9·5 - 12·6 IU ) or placebo ( vitamin E 9·5 - 12·6 IU ) within 72 h of birth . R and omisation was in blocks of 20 according to a r and omisation list prepared by a statistician not otherwise involved with the trial . Investigators , participants ' families , and the data analysis team were masked to treatment allocation . The primary outcome was mortality between supplementation and 6 months of age . Analysis included all participants assigned to study groups . This trial is registered with Clinical Trials.gov , number NCT01138449 , and the Indian Council of Medical Research Clinical Trial Registry , number CTRI/2010/091/000220 . FINDINGS Between June 24 , 2010 , and July 1 , 2012 we screened 47,777 neonates and r and omly assigned 44,984 to receive vitamin A ( 22,493 ) or placebo ( 22,491 ) . Between supplementation and 6 months of age , 656 infants died in the vitamin A group compared with 726 in the placebo group ( 29·2 per 1000 vs 32·3 per 1000 ; difference -3·1 per 1000 , 95 % CI -6·3 to 0·1 ; risk ratio 0·90 , 95 % CI 0·81 to 1·00 ) . We noted no significant interactions between the intervention effect and sex on mortality at 6 months ( p=0·409 ) . Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated , with the exception of a small excess risk of transient bulging fontanelle ( 205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group , risk ratio 2·56 [ 95 % CI 1·98 - 3·32 ] ) . INTERPRETATION The findings of this study , done in a population in which vitamin A deficiency is a moderate public health problem , are consistent with a modest reduction in mortality between supplementation and 6 months of age . These findings must be viewed together with similar trials in other population s to enable determination of appropriate public health policy . FUNDING Bill & Melinda Gates Foundation to WHO OBJECTIVE To test the safety , acceptability , feasibility , and effectiveness of community-based education and distribution of misoprostol for prevention of postpartum hemorrhage at home birth in Afghanistan . METHODS A nonr and omized experimental control design in rural Afghanistan . RESULTS A total of 3187 women participated : 2039 in the intervention group and 1148 in the control group . Of the 1421 women in the intervention group who took misoprostol , 100 % correctly took it after birth , including 20 women with twin pregnancies . Adverse effect rates were unexpectedly lower in the intervention group than in the comparison group . Among women in the intervention group , 92 % said they would use misoprostol in their next pregnancy . In the intervention area where community-based distribution of misoprostol was introduced , near-universal uterotonic coverage ( 92 % ) was achieved compared with 25 % coverage in the control areas . CONCLUSION In Afghanistan , community-based education and distribution of misoprostol is safe , acceptable , feasible , and effective . This strategy should be considered for other countries where access to skilled attendance is limited BACKGROUND About 500,000 sepsis-related deaths per year arise in the first 3 days of life . On the basis of results from non-r and omised studies , use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries . We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus . METHODS In a trial in Soweto , South Africa , 8011 women ( aged 12 - 51 years ) were r and omly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour , and their 8129 newborn babies were assigned to full-body ( intervention group ) or foot ( control group ) washes with chlorhexidine at birth , respectively . In a subset of mothers ( n=5144 ) , we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria . Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00136370 . FINDINGS Rates of neonatal sepsis did not differ between the groups ( chlorhexidine 141 [ 3 % ] of 4072 vs control 148 [ 4 % ] of 4057 ; p=0.6518 ) . Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine ( 217 [ 54 % ] of 401 ) and control groups ( 234 [ 55 % ] of 429 ] did not differ ( efficacy -0.05 % , 95 % CI -9.5 to 7.9 ) . INTERPRETATION Because chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or the vertical acquisition of potentially pathogenic bacteria among neonates , we need other interventions to reduce childhood mortality . FUNDING US Agency for International Development , National Vaccine Program Office and Centers for Disease Control 's Antimicrobial Resistance Working Group , and Bill & Melinda Gates Foundation BACKGROUND Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa . However , there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful . METHODS We did a r and omised , placebo-controlled trial , of children aged 1 - 35 months and living in Pemba , Zanzibar . We assigned children to daily oral supplementation with : iron ( 12.5 mg ) and folic acid ( 50 mug ; n=7950 ) , iron , folic acid , and zinc ( n=8120 ) , or placebo ( n=8006 ) ; children aged 1 - 11 months received half the dose . Our primary endpoints were all-cause mortality and admission to hospital . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59549825 . FINDINGS The iron and folic acid-containing groups of the trial were stopped early on Aug 19 , 2003 , on the recommendation of the data and safety monitoring board . To this date , 24 076 children contributed a follow-up of 25,524 child-years . Those who received iron and folic acid with or without zinc were 12 % ( 95 % CI 2 - 23 , p=0.02 ) more likely to die or need treatment in hospital for an adverse event and 11 % ( 1 - 23 % , p=0.03 ) more likely to be admitted to hospital ; there were also 15 % ( -7 to 41 , p=0.19 ) more deaths in these groups . INTERPRETATION Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death . In the presence of an active programme to detect and treat malaria and other infections , iron-deficient and anaemic children can benefit from supplementation . However , supplementation of those who are not iron deficient might be harmful . As such , current guidelines for universal supplementation with iron and folic acid should be revised BACKGROUND We undertook a multicentre r and omised controlled trial that compared the st and ard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits . METHODS Clinics in Argentina , Cuba , Saudi Arabia , and Thail and were r and omly allocated to provide either the new model ( 27 clinics ) or the st and ard model currently in use ( 26 clinics ) . All women presenting for antenatal care at these clinics over an average of 18 months were enrolled . Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions . Those who did not require further specific assessment or treatment were offered the basic component of the new model , and those deemed at higher risk received the usual care for their conditions ; however , all were included in the new-model group for the analyses , which were by intention to treat . The primary outcomes were low birthweight ( < 2500 g ) , pre-eclampsia/eclampsia , severe postpartum anaemia ( < 90 g/L haemoglobin ) , and treated urinary-tract infection . There was an assessment of quality of care and an economic evaluation . FINDINGS Women attending clinics assigned the new model ( n=12568 ) had a median of five visits compared with eight within the st and ard model ( n=11958 ) . More women in the new model than in the st and ard model were referred to higher levels of care ( 13.4 % vs 7.3 % ) , but rates of hospital admission , diagnosis , and length of stay were similar . The groups had similar rates of low birthweight ( new model 7.68 % vs st and ard model 7.14 % ; stratified rate difference 0.96 [ 95 % CI -0.01 to 1.92 ] ) , postpartum anaemia ( 7.59 % vs 8.67 % ; 0.32 ) , and urinary-tract infection ( 5.95 % vs 7.41 % ; -0.42 [ -1.65 to 0.80 ] ) . For pre-eclampsia/eclampsia the rate was slightly higher in the new model ( 1.69 % vs 1.38 % ; 0.21 [ -0.25 to 0.67 ] ) . Adjustment by several confounding variables did not modify this pattern . There were negligible differences between groups for several secondary outcomes . Women and providers in both groups were , in general , satisfied with the care received , although some women assigned the new model expressed concern about the timing of visits . There was no cost increase , and in some setting s the new model decreased cost . INTERPRETATIONS Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes . It could be implemented without major resistance from women and providers and may reduce cost BACKGROUND Up to half of neonatal deaths in high mortality setting s are due to infections , many of which can originate through the freshly cut umbilical cord stump . We aim ed to assess the effectiveness of two cord-cleansing regimens with the promotion of dry cord care in the prevention of neonatal mortality . DESIGN We did a community-based , parallel cluster-r and omised trial in Sylhet , Bangladesh . We divided the study area into 133 clusters , which were r and omly assigned to one of the two chlorhexidine cleansing regimens ( single cleansing as soon as possible after birth ; daily cleansing for 7 days after birth ) or promotion of dry cord care . R and omisation was done by use of a computer-generated sequence , stratified by cluster-specific participation in a previous trial . All livebirths were eligible ; those visited within 7 days by a local female village health worker trained to deliver the cord care intervention were enrolled . We did not mask study workers and participants to the study interventions . Our primary outcome was neonatal mortality ( within 28 days of birth ) per 1000 livebirths , which we analysed on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT00434408 . RESULTS Between June , 2007 , and September , 2009 , we enrolled 29 760 newborn babies ( 10 329 , 9423 , and 10 008 in the multiple-cleansing , single-cleansing , and dry cord care groups , respectively ) . Neonatal mortality was lower in the single-cleansing group ( 22·5 per 1000 livebirths ) than it was in the dry cord care group ( 28·3 per 1000 livebirths ; relative risk [ RR ] 0·80 [ 95 % CI ] 0·65 - 0·98 ) . Neonatal mortality in the multiple-cleansing group ( 26·6 per 1000 livebirths ) was not statistically significantly lower than it was in the dry cord care group ( RR 0·94 [ 0·78 - 1·14 ] ) . Compared with the dry cord care group , we recorded a statistically significant reduction in the occurrence of severe cord infection ( redness with pus ) in the multiple-cleansing group ( risk per 1000 livebirths=4·2 vs risk per 1000 livebirths=1·2 ; RR 0·35 [ 0·15 - 0·81 ] ) but not in the single-cleansing group ( risk per 1000 livebirths=3·3 ; RR 0·77 [ 0·40 - 1·48 ] ) . INTERPRETATION Chlorhexidine cleansing of a neonate 's umbilical cord can save lives , but further studies are needed to establish the best frequency with which to deliver the intervention . FUNDING United States Agency for International Development and Save the Children 's Saving Newborn Lives program , through a grant from the Bill & Melinda Gates Foundation OBJECTIVE : To estimate the effects of chlorhexidine vaginal and baby wipes on fetal and neonatal mortality , respectively , and infection-related morbidity . METHODS : We performed a placebo-controlled , r and omized trial of chlorhexidine vaginal and neonatal wipes to reduce neonatal sepsis and mortality in three hospitals in Pakistan . The primary study outcome was a composite of neonatal sepsis or 7-day perinatal mortality . RESULTS : From 2005 to 2008 , 5,008 laboring women and their neonates were r and omly assigned to receive either chlorhexidine wipes ( n=2,505 ) or wipes with a saline placebo ( n=2,503 ) . The primary outcome was similar in the chlorhexidine and control groups ( 3.1 % compared with 3.4 % ; relative risk 0.91 , 95 % confidence interval 0.67–1.24 ) as was the composite rate of neonatal sepsis or 28-day perinatal mortality ( 3.8 % compared with 3.9 % , relative risk 0.96 , 95 % confidence interval 0.73–1.27 ) . At day 7 , the chlorhexidine group had a lower rate of neonatal skin infection ( 3.3 % compared with 8.2 % , P<.001 ) . With the exception of less frequent 7-day hospitalization in the chlorhexidine group , there were no significant differences in maternal outcomes between the groups . CONCLUSION : Using maternal chlorhexidine vaginal wipes during labor and neonatal chlorhexidine wipes does not reduce maternal and perinatal mortality or neonatal sepsis . The finding of reduced superficial skin infections on day 7 without change in sepsis or mortality suggests that this difference , although statistically significant , may not be of major importance . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00121394 . LEVEL OF EVIDENCE : BACKGROUND Exclusive breastfeeding is recommended until age 6 months . We assessed the feasibility , effectiveness , and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India . METHODS We developed the intervention through formative research , pair-matched eight communities on their baseline characteristics , and r and omised one of each pair to receive the intervention and the other to no specific intervention . We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities . We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities . Feeding at age 3 months , and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed . All analyses were by intention to treat . FINDINGS We assessed 483 and 412 individuals at 3 months in the intervention and control groups , respectively , and 468 and 412 at 6 months . At 3 months , exclusive breastfeeding rates were 79 % ( 381 ) in the intervention and 48 % ( 197 ) in the control communities ( odds ratio 4.02 , 95 % CI 3.01 - 5.38 , p<0.0001 ) . The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months ( 0.64 , 0.44 - 0.95 , p=0.028 ) and 6 months ( 0.85 , 0.72 - 0.99 , p=0.04 ) . The mean weights and lengths , and the proportion with weight-for-height or height-for-age Z scores of 2 or less , at age 3 months and 6 months did not differ much between groups . Intervention effect on exclusive breastfeeding , diarrhoeal morbidity , and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births . INTERPRETATION Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible , reduces the risk of diarrhoea , and does not lead to growth faltering OBJECTIVE To determine feasibility of community-based distribution of misoprostol for preventing postpartum hemorrhage ( PPH ) to pregnant woman through community volunteers working under government health services . METHODS Implemented in one district in Nepal . The primary measure of performance was uterotonic protection after childbirth , measured using pre- and postintervention surveys ( 28 clusters , each with 30 households ) . Maternal deaths were ascertained through systematic health facility and community-based surveillance ; causes of death were assigned based on verbal autopsy . RESULTS Of 840 postintervention survey respondents , 73.2 % received misoprostol . The st and ardized proportion of vaginal deliveries protected by a uterotonic rose from 11.6 % to 74.2 % . Those experiencing the largest gains were the poor , the illiterate , and those living in remote areas . CONCLUSION Community-based distribution of misoprostol for PPH prevention can be successfully implemented under government health services in a low-re source , geographically challenging setting , result ing in much increased population -level protection against PPH , with particularly large gains among the disadvantaged Background Maternal malnutrition and poor gestational weight gain are the most important causes of low birth weight and high rates of newborn mortality . Objective To assess the effects of nutrition counseling in the third trimester of pregnancy on maternal weight gain , birth weight of newborn , and breastfeeding practice s. Methods This was a longitudinal experimental study with nutrition intervention for a period of 3 months . One hundred fifteen women ( 57 in the intervention group and 58 in the comparison group ) who were visiting the Maternal and Child Health Training Institute at 6 months of pregnancy were r and omly selected . The intervention group was given nutrition education twice in the first month and once a month for the next 2 months before delivery ; the comparison group received routine hospital advice on food intake , immunization , personal hygiene , and breastfeeding . The women were weighed monthly up to delivery , the newborn infants ' birth weights were measured within 24 hours after delivery , and breastfeeding practice s were observed 1 month after delivery . Results Women in the intervention group gained 1.73 kg more weight during the third trimester than women in the comparison group ( 5.61 vs. 3.88 kg , p < 0.001 ) . The mean birthweight of babies of women in the intervention group was 0.44 kg greater than that of babies of women in the comparison group ( 2.86 vs. 2.42 kg , p < 0.001 ) . In the intervention group , 10.5 % of babies were born with low birthweight , compared with 48.3 % of the babies of women in the comparison group ( p < 0.001 ) . In the intervention group , 75.4 % of mothers initiated breastfeeding within 1 hour after birth , compared with 34.5 % of mothers in the comparison group ( p < 0.001 ) . Conclusions Nutrition education only during the third trimester improved weight gain during pregnancy , reduced 78 % of low birth weight , and improved breast-feeding practice OBJECTIVE The objective of this study was to determine if cleansing the birth canal with an antiseptic solution at delivery reduces infections in mothers and their newborn babies . METHODS Women giving birth in the University Hospital , Alex and ria , and their newborns were studied . No intervention for 3 months was followed by 3 months of intervention . Intervention consisted of manually wiping the maternal birth canal with a 0.25 % chlorhexidine solution at admission and at every vaginal examination before delivery . Babies were also wiped with chlorhexidine . RESULTS The study enrolled 4415 women and 4431 newborns . The nonintervention phase comprised 2128 mothers and 2138 newborns , and 2287 mothers and 2293 babies were enrolled in the intervention phase . There were no adverse reactions related to the intervention among the mothers or their children . There was no difference in the overall number of neonatal admissions in both groups , but the admissions because of infection , deaths , and mortalities from infection were significantly less in the intervention group . Among mothers receiving the intervention , admissions , deaths , and infections were significantly reduced . CONCLUSIONS Cleansing the birth canal with chlorhexidine reduced neonatal and maternal postpartum infections . The safety , simplicity , and low cost of the procedure suggest that it should be considered st and ard care for the reduction of infant and maternal morbidity and mortality OBJECTIVES Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus , unresolved questions remain concerning the required minimum number of doses and the result ing duration of effective immunity . This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization . METHODS A r and omized , double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues . RESULTS Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers . Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent duration s of up to 12 or 13 years . CONCLUSIONS The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death BACKGROUND Large reductions in transmission of HIV-1 from mother to child have been achieved in more-developed countries due to the use of antiretrovirals . Short-course regimens , suitable for re source -poor countries , have also been shown to significantly reduce peripartum HIV-1 transmission . We assessed the efficacy of short-course regimens with zidovudine and lamivudine in a predominantly breastfeeding population . METHODS We did a r and omised , double-blind , placebo-controlled trial in South Africa , Ug and a , and Tanzania . Between June , 1996 , and January , 2000 , HIV-1-infected mothers were r and omised to one of four regimens : A , zidovudine plus lamivudine starting at 36 weeks ' gestation , followed by oral intrapartum dosing and by 7 days ' postpartum dosing of mothers and infants ; B , as regimen A , but without the prepartum component ; C , intrapartum zidovudine and lamivudine only ; or placebo . From Feb 18 , 1998 , onward , women were only r and omised to one of the active treatment groups . Primary outcomes were HIV-1 infection and child mortality at week 6 and month 18 after birth . Analysis was by intention to treat of those r and omised before Feb 18 , 1998 . FINDINGS 1797 HIV-1-infected women were identified . Week 6 HIV-1 transmission rates were 5.7 % for group A , 8.9 % for group B , 14.2 % for group C , and 15.3 % for the placebo group . Respective relative risks for HIV-1 transmission in the treatment groups compared with placebo were 0.37 ( 95 % CI 0.21 - 0.65 ) , 0.58 ( 0.36 - 0.94 ) , and 0.93 ( 0.62 - 1.40 ) . For the combined endpoint of HIV-1 infection and infant mortality at week 6 rates were 7.0 % , 11.6 % , 17.5 % , and 18.1 % , respectively , with relative risks of 0.39 ( 0.24 - 0.64 ) , 0.64 ( 0.42 - 0.97 ) , and 0.97 ( 0.68 - 1.38 ) . 1081 ( 74 % ) of the women analysed initiated breastfeeding . Based on an interval-censored survival analysis , HIV-1 infection rates at month 18 were 15 % ( 95 % CI 9 - 23 ) , 18 % ( 12 - 26 ) , 20 % ( 13 - 30 ) and 22 % ( 16 - 30 ) , respectively . INTERPRETATION Although at week 6 after birth , regimens A and B were effective in reducing HIV-1 transmission , benefits have diminished considerably after 18 months of follow-up . Introduction of short-course regimens to prevent mother-to-child transmission of HIV-1 in less-developed countries should be accompanied by interventions to minimise the risk of subsequent transmission via breastfeeding Intermittent preventive treatment of malaria during pregnancy ( IPTp ) and insecticide-treated nets ( ITN ) are recommended malaria interventions during pregnancy ; however , there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa . An individually-r and omised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp , ITNs alone , or ITNs used in combination with IPTp on maternal anaemia and low birth weight ( LBW ) in a highl and area of southwestern Ug and a. The overall prevalence of malaria infection , maternal anaemia and LBW was 15.0 % , 14.7 % and 6.5 % , respectively . Maternal and fetal outcomes were generally remarkably similar across all intervention groups ( P>0.05 for all outcomes examined ) . A marginal difference in maternal haemoglobin was observed in the dual intervention group ( 12.57g/dl ) compared with the IPTp and ITN alone groups ( 12.40g/dl and 12.44g/dl , respectively ; P=0.04 ) , but this was too slight to be of clinical importance . In conclusion , none of the preventive strategies was found to be superior to the others , and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed . With ITNs offering a number of advantages over IPTp , yet showing comparable efficacy , we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission The last decades of the 20th century witnessed a major epidemiological and nutritional transition in Latin America . Mortality due to infectious diseases and malnutrition declined in most countries and neonatal deaths now account for a growing proportion of infant deaths . In Brazil , infant mortality fell from 82.8 per 1000 live births in 1980 to 27.4 per 1000 in 2000 . There were also marked improvements in undernutrition : 37.1 % of Brazilian children < 5 years of age were stunted in 1974 compared with 10.5 % in 1996 . Because of the speed of epidemiological and nutritional changes , and motivated by the successful implementation and follow-up of two previous population -based birth cohorts in 1982 and 1993 , the research team decided to start a new cohort in 2004 to assess the magnitude of changes in maternal and child health status and their determinants . The existence of three prospect i ve birth cohorts in the same population would provide a unique opportunity to study time trends over a 22-year span Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates . Design R and omised , placebo controlled , two by two factorial trial . Setting Bissau , Guinea-Bissau . Participants 1717 low birthweight neonates born at the national hospital . Intervention Neonates who weighed less than 2.5 kg were r and omly assigned to 25 000 IU vitamin A or placebo , as well as to early BCG vaccine or the usual late BCG vaccine , and were followed until age 12 months . Main outcome measure Mortality , calculated as mortality rate ratios ( MRRs ) , after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo . Results No interaction was observed between vitamin A supplementation and BCG vaccine allocation ( P=0.73 ) . Vitamin A supplementation at birth was not significantly associated with mortality : the MRR of vitamin A supplementation compared with placebo , controlled for r and omisation to “ early BCG ” versus “ no early BCG ” was 1.08 ( 95 % CI 0.79 to 1.47 ) . Stratification by sex revealed a significant interaction between vitamin A supplementation and sex ( P=0.046 ) , the MRR of vitamin A supplementation being 0.74 ( 95 % CI 0.45 to 1.22 ) in boys and 1.42 ( 95 % CI 0.94 to 2.15 ) in girls . When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau , the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 ( 95 % CI 0.87 to 1.33 ) ; 0.80 ( 95 % CI 0.58 to 1.10 ) in boys and 1.41 ( 95 % CI 1.04 to 1.90 ) in girls ( P=0.01 for interaction between neonatal vitamin A and sex ) . Conclusions The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that , overall , it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau . Worryingly , the trials show that vitamin A supplementation at birth can be harmful in girls . Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects . Trial registration Clinical Trials.gov NCT00168610 OBJECTIVES . We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality through 24 weeks of age . PATIENTS AND METHODS . This was a community-based , double-masked , cluster-r and omized , placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh . The study was nested into and balanced across treatment arms of an ongoing placebo-controlled , weekly maternal vitamin A or β-carotene supplementation trial . Study -defined sectors ( N = 596 ) were evenly r and omized for newborns of participating mothers to receive a single , oral supplement of vitamin A ( 50000 IU ) or placebo as droplets of oil squeezed from a gelatinous capsule . Mothers provided informed consent for newborn participation at ∼28 weeks ' gestation . After birth , typically at home ( where > 90 % of births occurred ) , infants were supplemented and their vital status was followed through 24 weeks of age . The main outcome measure was mortality through 24 weeks of age . RESULTS . We obtained maternal consent to dose 17116 live-born infants ( 99.8 % of all eligible ) among whom 15937 ( 93.1 % ) were visited to be supplemented < 30 days after birth and for whom vital status at 24 weeks of age was known . Dosed infants ( n = 15902 [ 99.8 % ] ) received their study supplement at a median age of 7 hours . Relative to control subjects , the risk of death in vitamin A – supplemented infants was 0.85 , reflecting a 15 % reduction in all-cause mortality . Protective relative risks were indistinguishable by infant gender , gestational age , birth weight , age at dosing , maternal age , parity , or across the 3 treatment arms of the maternal supplementation trial . CONCLUSIONS . Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh . These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia BACKGROUND Exclusive breastfeeding ( EBF ) is reported to be a life-saving intervention in low-income setting s. The effect of breastfeeding counselling by peer counsellors was assessed in Africa . METHODS 24 communities in Burkina Faso , 24 in Ug and a , and 34 in South Africa were assigned in a 1:1 ratio , by use of a computer-generated r and omisation sequence , to the control or intervention clusters . In the intervention group , we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers . The data gathering team were masked to the intervention allocation . The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks . Country-specific prevalence ratios were adjusted for cluster effects and sites . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00397150 . FINDINGS 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso ( n=392 and n=402 , respectively ) , Ug and a ( n=396 and n=369 , respectively ) , and South Africa ( n=535 and 485 , respectively ) . The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 ( 79 % ) of 392 and 139 ( 35 % ) of 402 , respectively , in Burkina Faso ( prevalence ratio 2·29 , 95 % CI 1·33 - 3·92 ) ; 323 ( 82 % ) of 396 and 161 ( 44 % ) of 369 , respectively , in Ug and a ( 1·89 , 1·70 - 2·11 ) ; and 56 ( 10 % ) of 535 and 30 ( 6 % ) of 485 , respectively , in South Africa ( 1·72 , 1·12 - 2·63 ) . The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 ( 77 % ) and 94 ( 23 % ) , respectively , in Burkina Faso ( 3·27 , 2·13 - 5·03 ) ; 305 ( 77 % ) and 125 ( 34 % ) , respectively , in Ug and a ( 2·30 , 2·00 - 2·65 ) ; and 41 ( 8 % ) and 19 ( 4 % ) , respectively , in South Africa ( 1·98 , 1·30 - 3·02 ) . At 24 weeks , the prevalences based on 24-h recall were 286 ( 73 % ) in the intervention cluster and 88 ( 22 % ) in the control cluster in Burkina Faso ( 3·33 , 1·74 - 6·38 ) ; 232 ( 59 % ) and 57 ( 15 % ) , respectively , in Ug and a ( 3·83 , 2·97 - 4·95 ) ; and 12 ( 2 % ) and two ( < 1 % ) , respectively , in South Africa ( 5·70 , 1·33 - 24·26 ) . The prevalences based on 7-day recall were 279 ( 71 % ) in the intervention cluster and 38 ( 9 % ) in the control cluster in Burkina Faso ( 7·53 , 4·42 - 12·82 ) ; 203 ( 51 % ) and 41 ( 11 % ) , respectively , in Ug and a ( 4·66 , 3·35 - 6·49 ) ; and ten ( 2 % ) and one ( < 1 % ) , respectively , in South Africa ( 9·83 , 1·40 - 69·14 ) . Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 ( 5 % ) and 36 ( 9 % ) , respectively , in Burkina Faso ( 0·57 , 0·27 - 1·22 ) ; 39 ( 10 % ) and 32 ( 9 % ) , respectively , in Ug and a ( 1·13 , 0·81 - 1·59 ) ; and 45 ( 8 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·16 , 0·78 - 1·75 ) . The prevalence at age 24 weeks in the intervention and control clusters was 26 ( 7 % ) and 32 ( 8 % ) , respectively , in Burkina Faso ( 0·83 , 0·45 - 1·54 ) ; 52 ( 13 % ) and 59 ( 16 % ) , respectively , in Ug and a ( 0·82 , 0·58 - 1·15 ) ; and 54 ( 10 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·31 , 0·89 - 1·93 ) . INTERPRETATION Low-intensity individual breastfeeding peer counselling is achievable and , although it does not affect the diarrhoea prevalence , can be used to effectively increase EBF prevalence in many sub-Saharan African setting s. FUNDING European Union Sixth Framework International Cooperation-Developing Countries , Research Council of Norway , Swedish International Development Cooperation Agency , Norwegian Programme for Development , Research and Education , South African National Research Foundation , and Rockefeller Brothers Foundation Abstract Objective : To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women . Design : Double blind cluster r and omised controlled trial . Setting : Rural community in south eastern Nepal . Participants : 4926 pregnant women and 4130 live born infants . Interventions : 426 communities were r and omised to five regimens in which pregnant women received daily supplements of folic acid , folic acid-iron , folic acid-iron-zinc , or multiple micronutrients all given with vitamin A , or vitamin A alone ( control ) . Main outcome measures : Birth weight , length , and head and chest circumference assessed within 72 hours of birth . Low birth weight was defined < 2500 g. Results : Supplementation with maternal folic acid alone had no effect on birth size . Folic acid-iron increased mean birth weight by 37 g ( 95 % confidence interval −16 g to 90 g ) and reduced the percentage of low birthweight babies ( < 2500 g ) from 43 % to 34 % ( 16 % ; relative risk=0.84 , 0.72 to 0.99 ) . Folic acid-iron-zinc had no effect on birth size compared with controls . Multiple micronutrient supplementation increased birth weight by 64 g ( 12 g to 115 g ) and reduced the percentage of low birthweight babies by 14 % ( 0.86 , 0.74 to 0.99 ) . None of the supplement combinations reduced the incidence of preterm births . Folic acid-iron and multiple micronutrients increased head and chest circumference of babies , but not length . Conclusions : Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight . Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk . What is already known on this topic Deficiencies in micronutrients are common in women in developing countries and have been associated with low birth weight and preterm delivery What this study adds In rural Nepal maternal supplementation with folic acid-iron reduced the incidence of low birth weight by 16 % A multiple micronutrient supplement of 14 micronutrients , including folic acid , iron , and zinc , reduced low birth weight by 14 % , thus conferring no advantage over folic Objective : To examine the association between breast-feeding initiation time and neonatal mortality in India , where breast-feeding initiation varies widely from region to region . Study Design : Data were collected as part of a community-based , r and omized , placebo-controlled trial of the impact of vitamin A supplementation in rural villages of Tamil Nadu , India . Multivariate binomial regression analysis was used to estimate the association between neonatal mortality and breast-feeding initiation time ( < 12 h , 12 to 24 h , > 24 h ) among infants surviving a minimum of 48 h. Result : Among 10 464 newborns , 82.1 % were first breast-fed before 12 h , 13.8 % were breast-fed between 12 and 24 h , and 4.1 % were breast-fed after 24 h. After adjusting for birth weight , gestational age and other covariates , late initiators ( > 24 h ) were at ∼78 % higher risk of death ( relative risk=1.78 ( 95 % confidence interval (CI)=1.03 to 3.10 ) ) . There was no difference in mortality risk when comparing babies fed in the first 12 h compared with the second 12 h after birth . Conclusion : Late ( > 24 h ) initiation of breast-feeding is associated with a higher risk of neonatal mortality in Tamil Nadu . Emphasis on breast-feeding promotion programs in low-re source setting s of India where early initiation is low could significantly reduce neonatal mortality OBJECTIVE To determine whether vitamin A supplementation at birth could reduce infant morbidity and mortality . STUDY DESIGN We conducted a placebo-controlled trial among 2067 Indonesian neonates who received either 52 micromol ( 50,000 IU ) orally administered vitamin A or placebo on the first day of life . Infants were followed up at 1 year to determine the impact of this intervention on infant mortality . A subgroup ( n = 470 ) was also examined at 4 and 6 months of age to examine the impact on morbidity . RESULTS Vital status was confirmed in 89 % of infants in both groups at 1 year . There were 19 deaths in the control group and 7 in the vitamin A group ( relative risk = 0.36 ; 95 % confidence interval = 0.16 , 0.87 ) . The impact was stronger among boys , infants of normal compared with low birth weight , and those of greater ponderal index . Among infants examined at 4 months of age , the 1-week period prevalence of common morbidities was similar for vitamin A and control infants . However , during this same 4-month period , 73 % and 51 % more control infants were brought for medical treatment for cough ( p = 0.008 ) and fever ( p = 0.063 ) , respectively . CONCLUSIONS Neonatal vitamin A supplementation may reduce the infant mortality rate and the prevalence of severe respiratory infection among young infants Anthelmintic treatment , which is recommended during pregnancy in areas where there is a high rate of anaemia , needs further investigation . We examined prospect ively the association between anthelmintic treatment and maternal anaemia , birthweight , and infant mortality in a study of prenatal supplements , in which women received albendazole twice during pregnancy . Women given albendazole in the second trimester of pregnancy had a lower rate of severe anaemia during the third trimester . Birthweight of infants of women who had received two doses of albendazole rose by 59 g ( 95 % CI 19 - 98 ) , and infant mortality at 6 months fell by 41 % ( RR 0.59 ; 95 % CI 0.43 - 0.82 ) . Antenatal anthelmintics could be effective in reducing maternal anaemia and improving birthweight and infant survival in hookworm-endemic regions CONTEXT Maternal vitamin A deficiency is a public health concern in the developing world . Its prevention may improve maternal and infant survival . OBJECTIVE To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized , double-masked , placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks ( 84 days ) postpartum in rural northern Bangladesh between 2001 and 2007 . Interventions Five hundred ninety-six community clusters ( study sectors ) were r and omized for pregnant women to receive weekly , from the first trimester through 12 weeks postpartum , 7000 μg of retinol equivalents as retinyl palmitate , 42 mg of all-trans beta carotene , or placebo . Married women ( n = 125,257 ) underwent 5-week surveillance for pregnancy , ascertained by a history of amenorrhea and confirmed by urine test . Blood sample s were obtained from participants in 32 sectors ( 5 % ) for biochemical studies . MAIN OUTCOME MEASURES All-cause mortality of women related to pregnancy , stillbirth , and infant mortality to 12 weeks ( 84 days ) following pregnancy outcome . RESULTS Groups were comparable across risk factors . For the mortality outcomes , neither of the supplement group outcomes was significantly different from the placebo group outcomes . The numbers of deaths and all-cause , pregnancy-related mortality rates ( per 100,000 pregnancies ) were 41 and 206 ( 95 % confidence interval [ CI ] , 140 - 273 ) in the placebo group , 47 and 237 ( 95 % CI , 166 - 309 ) in the vitamin A group , and 50 and 250 ( 95 % CI , 177 - 323 ) in the beta carotene group . Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 ( 95 % CI , 0.75 - 1.76 ) and 1.21 ( 95 % CI , 0.81 - 1.81 ) , respectively . In the placebo , vitamin A , and beta carotene groups the rates of stillbirth and infant mortality were 47.9 ( 95 % CI , 44.3 - 51.5 ) , 45.6 ( 95 % CI , 42.1 - 49.2 ) , and 51.8 ( 95 % CI , 48.0 - 55.6 ) per 1000 births and 68.1 ( 95 % CI , 63.7 - 72.5 ) , 65.0 ( 95 % CI , 60.7 - 69.4 ) , and 69.8 ( 95 % CI , 65.4 - 72.3 ) per 1000 live births , respectively . Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study ( 1.46 [ 95 % CI , 1.42 - 1.50 ] μmol/L vs 1.13 [ 95 % CI , 1.09 - 1.17 ] μmol/L and 1.18 [ 95 % CI , 1.14 - 1.22 ] μmol/L , respectively ; P < .001 ) and reduced , but did not eliminate , gestational night blindness ( 7.1 % for vitamin A vs 9.2 % for placebo and 8.9 % for beta carotene [ P < .001 for both ] ) . CONCLUSION Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh , compared with placebo , did not reduce all-cause maternal , fetal , or infant mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00198822 BACKGROUND The benefits and safety of vitamin A supplementation linked to immunisation in infancy need to be assessed before it can be widely recommended . We assessed the safety and benefits of maternal postpartum and infant vitamin A supplementation administered with each of the three diphtheria-tetanus-pertussis ( DPT ) and poliomyelitis immunisations and with a fourth dose with measles immunisation . METHODS From January , 1995 , we enrolled 9424 mother-infant pairs from Ghana , India , and Peru in this r and omised , double-blind , placebo-controlled trial . 4716 mothers of infants in the vitamin A group received 200000 IU vitamin A , and their infants were given 25000 IU vitamin A with each of the first three doses of DPT/poliomyelitis immunisation at 6 , 10 , and 14 weeks . In the control group , 4708 mothers and their infants received placebo at the same times . At 9 months , with measles immunisation , infants in the vitamin A group were given a further dose of 25000 IU and those in the control group received 100000 IU vitamin A. Infants were followed up to age 12 months . The primary outcome measures were vitamin A status , signs of acute toxic effects , anthropometric indicators , and severe morbidity . Analysis was by intention to treat . FINDINGS 3933 ( 93 % ) of the eligible 4212 infants on vitamin A and 3938 ( 93 % ) of the eligible 4227 controls received all four study doses . At the 6-month follow-up , there was a small decrease in vitamin A deficiency in the vitamin A group compared with controls ( serum retinol < or = 0.70 micromol/L 101 [ 29.9 % ] vs 122 [ 37.1 % ; 95 % CI of the difference -14.3 % to -0.2 % ] ) . This effect was no longer apparent at 9 and 12 months . There were no significant between-group differences in mortality throughout the study . The rate ratio to compare all deaths up to age 9 months in the two groups was 0.96 ( 95 % CI 0.73 to 1.27 ) . Fewer than 1 % of the infants had bulging fontanelle . The intervention had no effect on anthropometric status , or on overall or severe morbidity . INTERPRETATION The trial confirmed the safety of the intervention , but shows no sustained benefits in terms of vitamin A status beyond age 6 months or infant morbidity BACKGROUND In 2009 , on the basis of promising evidence from trials in south Asia , WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival . In the Newhints trial , we aim ed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate ( NMR ) and essential newborn-care practice s. METHODS The Newhints cluster r and omised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region , Ghana . 49 zones were r and omly assigned to the Newhints intervention and 49 to the control intervention by use of restricted r and omisation with stratification to ensure comparability between interventions . Community-based surveillance volunteers ( CBSVs ) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practice s , weigh and assess babies for danger signs , and refer as necessary . Primary outcomes were NMR and coverage of key essential newborn-care practice s. Analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00623337 . FINDINGS 16,168 ( 99 % ) of 16,329 deliveries between November , 2008 , and December , 2009 , were livebirths ; the status at 1 month was known for 15,619 ( 97 % ) livebirths . 482 neonatal deaths were recorded . Coverage data were available from 6029 women in Newhints zones ; of these 4358 ( 72 % ) reported having CBSV visits during pregnancy and 3815 ( 63 % ) reported having postnatal visits . This coverage increased substantially from June , 2009 , after the introduction of new implementation strategies and reached almost 90 % for pregnancy visits by the end of the trial and 75 % for postnatal visits . The Newhints intervention significantly increased coverage of key essential newborn-care behaviours , except for four or more antenatal-care visits ( 5975 [ 76 % ] of 7859 vs 5988 [ 74 % ] of 8121 , respectively ; relative risk 1·02 , 95 % CI 0·96 - 1·09 ; p=0·52 ) and baby delivered in a facility ( 5373 [ 68 % ] vs 5539 [ 68 % ] , respectively ; 0·97 , 0·81 - 1·14 ; p=0·69 ) . The largest increase was for care-seeking , with 102 ( 77 % ) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 ( 55 % ) of 139 in control zones ( 1·43 , 1·17 - 1·76 ; p=0·001 ) . Increases were also noted in bednet use during pregnancy ( 5398 [ 69 % ] of 7859 vs 5135 [ 63 % ] of 8121 , respectively ; 1·12 , 1·03 - 1·21 ; p=0·005 ) , money saved for delivery or emergency ( 5730 [ 86 % ] of 6681 vs 5525 [ 80 % ] of 6941 , respectively ; 1·09 , 1·05 - 1·12 ; p<0·0001 ) , transport arranged in advance for facility ( 2496 [ 37 % ] vs 2061 [ 30 % ] , respectively ; 1·30 , 1·12 - 1·49 ; p=0·0004 ) , birth assistant for home delivery washed h and s with soap ( 1853 [ 93 % ] of 1992 vs 1817 [ 87 % ] of 2091 , respectively ; 1·05 , 1·02 - 1·09 ; p=0·001 ) , initiation of breastfeeding in less than 1 h of birth ( 3743 [ 49 % ] of 7673 vs 3280 [ 41 % ] of 7921 , respectively ; 1·22 , 1·07 - 1·40 ; p=0·004 ) , skin to skin contact ( 3355 [ 44 % ] vs 1931 [ 24 % ] , respectively ; 2·30 , 1·85 - 2·87 ; p=0·0002 ) , first bath delayed for longer than 6 h ( 3131 [ 41 % ] vs 2269 [ 29 % ] , respectively ; 1·65 , 1·27 - 2·13 ; p<0·0001 ) , exclusive breastfeeding for 26 - 32 days ( 1217 [ 86 % ] of 1414 vs 1091 [ 80 % ] of 1371 ; 1·10 , 1·04 - 1·16 ; p=0·001 ) , and baby sleeping under bednet for 8 - 56 days ( 4548 [ 79 % ] of 5756 vs 4291 [ 73 % ] of 5846 ; 1·09 , 1·03 - 1·15 ; p=0·002 ) . There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones . The overall NMRs per 1000 livebirths were 29·8 and 31·9 , respectively ( 0·92 , 0·75 - 1·12 ; p=0·405 ) . INTERPRETATION The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme setting s in south Asia . Because there is no suggestion of any heterogeneity ( p=0·850 ) between these trials and Newhints , the meta- analysis summary estimate of a reduction of 12 % ( 95 % CI 5 - 18 ) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia . Improvements in the quality of delivery and neonatal care in health facilities and development of innovative , effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions . FUNDING WHO , Bill & Melinda Gates Foundation , and UK Department for International Development Abstract Objective To determine the influence of multiple contraceptive counselling sessions during antenatal care on use of modern postpartum contraception . Method A total of 216 eligible pregnant women were r and omised into antenatal and postnatal counselling groups . The ‘ Antenatal group ’ received one-to-one antenatal contraceptive counselling on several occasions while the ‘ Postnatal group ’ received a single one-to-one contraceptive counselling session at the sixth week postnatal check , as is routinely practised . All participants were contacted six months postpartum by telephone or personal visit , and question ed about their contraceptive use , if any . Results More women who had multiple antenatal contraceptive counselling sessions used modern contraceptive methods than those who had a single postnatal counselling session ( 57 % vs. 35 % ; p = 0.002 ) . There was also a significantly more frequent use of contraception among previously undecided patients in the Antenatal group ( p = 0.014 ) . Conclusion Multiple antenatal contraceptive counselling sessions improve the use of modern postpartum contraception BACKGROUND In sub-Saharan Africa , most women present late for delivery with unknown HIV status , which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV . We aim ed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone . METHODS We r and omly assigned 1119 babies of Malawian women with HIV-1 who presented late ( ie , within 2 h of expected delivery ) to either nevirapine alone or nevirapine and zidovudine . Both drugs were given immediately after birth : one dose of nevirapine ( 2 mg/kg weight ) was given as a single dose ; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week ( 4 mg/kg weight ) . Infant HIV infection was determined at birth and at 6 - 8 weeks . Primary outcome was HIV infection in babies at 6 - 8 weeks in those not infected at birth . Analysis was by intention to treat . FINDINGS The overall rate of mother-to-child transmission at 6 - 8 weeks was 15.3 % in 484 babies who received nevirapine and zidovudine and 20.9 % in 468 babies who received nevirapine only ( p=0.03 ) . At 6 - 8 weeks , in babies who were HIV negative at birth , 34 ( 7.7 % ) babies who had nevirapine and zidovudine and 51 ( 12.1 % ) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36 % . This finding remained after controlling for maternal viral load and other factors at baseline . Adverse events were mild and of similar frequency in the two groups . INTERPRETATION Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy . The nevirapine and zidovudine regimen is safe and easy to implement The impact of antenatal counselling on couples ' knowledge and practice of contraception was investigated . An interview question naire was used before and after conducting counselling sessions with 200 pregnant women and 100 spouses . The participants were followed up immediately after delivery and 3 months later . Both the control and study groups displayed a lack of knowledge of contraception . Counselling sessions improved the couples ' knowledge and practice in the study group . Involving husb and s in family planning counselling sessions led to joint decisions being made and encouraged women 's use of contraception . The majority of couples retained most of the information given . Integrating family planning counselling into antenatal care in all facilities and involving the husb and are recommended With a view to determining the effectiveness of a method for the control of tetanus neonatorum which would be independent of medical examination or care , a double-blind field trial covering 1618 women was conducted between 1961 and 1966 in a rural area of Colombia with an estimated existing tetanus neonatorum death rate of 11.6 per 100 births . The study group was given 1 - 3 injections of 1 ml of an aluminium-phosphate-adsorbed tetanus toxoid more than 6 weeks apart , and the control group a similar number of injections of an influenza-virus vaccine . There was no statistically significant difference between those in the two groups given one injection . Those in the control group given 2 or 3 injections had a tetanus neonatorum death rate of 7.8 deaths per 100 births , and the corresponding subjects in the study group had none . This difference is unlikely to have occurred by chance BACKGROUND Umbilical cord infection ( omphalitis ) is a risk factor for neonatal sepsis and mortality in low-re source setting s where home deliveries are common . We aim ed to assess the effect of umbilical-cord cleansing with 4 % chlorhexidine ( CHX ) solution , with or without h and washing with antiseptic soap , on the incidence of omphalitis and neonatal mortality . METHODS We did a two-by-two factorial , cluster-r and omised trial in Dadu , a rural area of Sindh province , Pakistan . Clusters were defined as the population covered by a functional traditional birth attendant ( TBA ) , and were r and omly allocated to one of four groups ( groups A to D ) with a computer-generated r and om number sequence . Implementation and data collection teams were masked to allocation . Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study . One intervention comprised birth kits containing 4 % CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting h and washing . One intervention was CHX solution only and another was h and washing only . St and ard dry cord care was promoted in the control group . The primary outcomes were incidence of neonatal omphalitis and neonatal mortality . The trial is registered with Clinical Trials.gov , number NCT00682006 . FINDINGS 187 clusters were r and omly allocated to one of the four study groups . Of 9741 newborn babies delivered by participating TBAs , factorial analysis indicated a reduction in risk of omphalitis with CHX application ( risk ratio [RR]=0·58 , 95 % CI 0·41 - 0·82 ; p=0·002 ) but no evidence of an effect of h and washing ( RR=0·83 , 0·61 - 1·13 ; p=0·24 ) . We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing ( RR=0·62 , 95 % CI 0·45 - 0·85 ; p=0·003 ) but no evidence of an effect of h and washing promotion on neonatal mortality ( RR=1·08 , 0·79 - 1·48 ; p=0·62 ) . We recorded no serious adverse events . INTERPRETATION Application of 4 % CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan . Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high-mortality setting s. FUNDING The United States Agency for International Development Low birth weight , prematurity , and intrauterine growth retardation represent important health tasks for neonates . Pregnancy outcome risk categories based on combinations of these variables and a measure of body proportions were developed and tested with respect to how well they predict poor growth during infancy . Data were collected during a prospect i ve community-based survey of births representative of the Cebu region of the Philippines . In the sample of 2139 births for which there were available birth weight and gestational age data , 20 % of infants were classified as growth retarded and 12 % were low birth weight . Low birth weight , the more conservative category , was a better predictor of small infant size at 12 months of age than intrauterine growth retardation . Rohrer 's index , which captures information about patterns of intrauterine growth , improves the positive predictive value of categories based either on intrauterine growth retardation or low birth weight . Infants who had an adequate Rohrer 's index , ie , were well proportioned at birth , were smaller at 12 months of age than infants who had a low Rohrer 's index , ie , had weight deficits relative to their lengths at birth . Important questions about the value of the intrauterine growth retardation classification are raised by the results BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh . Therefore the project for advancing the health of newborns and mothers ( Projahnmo ) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality . METHODS In Sylhet district , 24 clusters ( with a population of about 20 000 each ) were r and omly assigned in equal numbers to one of two intervention arms or to the comparison arm . Because of the study design , masking was not feasible . All married women of reproductive age ( 15 - 49 years ) were eligible to participate . In the home-care arm , female community health workers ( one per 4000 population ) identified pregnant women , made two antenatal home visits to promote birth and newborn-care preparedness , made postnatal home visits to assess newborns on the first , third , and seventh days of birth , and referred or treated sick neonates . In the community-care arm , birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers . The primary outcome was reduction in neonatal mortality . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number 00198705 . FINDINGS The number of clusters per arm was eight . The number of participants was 36059 , 40159 , and 37598 in the home-care , community-care , and comparison arms , respectively , with 14 769 , 16 325 , and 15 350 livebirths , respectively . In the last 6 months of the 30-month intervention , neonatal mortality rates were 29.2 per 1000 , 45.2 per 1000 , and 43.5 per 1000 in the home-care , community-care , and comparison arms , respectively . Neonatal mortality was reduced in the home-care arm by 34 % ( adjusted relative risk 0.66 ; 95 % CI 0.47 - 0.93 ) during the last 6 months versus that in the comparison arm . No mortality reduction was noted in the community-care arm ( 0.95 ; 0.69 - 1.31 ) . INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system , low health-care use , and high neonatal mortality & NA ; We performed this r and omized trial to determine whether infants receiving skin‐to‐skin care ( SSC ) grew more rapidly and had a shorter duration of hospital stay compared with infants held by their parents in a traditional way . Infants who met eligibility criteria ( ≤32 wk of gestation , ≤1500 g , minimal ventilatory support , and hemodynamically stable ) were r and omized to traditional holding ( TH ) or SSC groups . Parents in both groups were allowed to hold infants for a total of 8 hours per day ( periods of up to 4 hr , twice/d ) . During the study , infants in the TH group were held 4.8 ± 3.5 times per week and 76 ± 39 minutes per day , and infants in the SSC group were held 4.0 ± 2.8 times per week and 79 ± 40 minutes per day . No significant differences were observed in weight accretion or linear growth . However , exposure to SSC was associated with greater head growth , even after controlling for head circumference at birth ( p = .03 ) . SSC may increase the likelihood of successful breastfeeding . J Dev Behav Pediatr 24:163‐168 , 2003 . Index terms : skin‐to‐skin care , growth A prospect i ve observational study of post‐delivery care and neonatal body temperature , carried out at Kathm and u Maternity Hospital , was followed by a r and omized controlled intervention study using three simple methods for maintaining body temperature . There were 500 infants in the initial observation study and 300 in the intervention study . In the observation study , 85 % ( 420/495 ) of infants had temperatures < 36 ° C at 2 h and nearly 50 % ( 198/405 ) had temperatures < 36 ° C at 24 h ( 14 % were < 35 ° C ) . Most of the infants who were cold at 24 h had initially become cold at the time of delivery ( only seven infants had been both well dried and wrapped ) . In the intervention study , all infants were dried and wrapped before r and om assignment to one of the three methods : the “ kangaroo ” method , the traditional “ oil massage ” or a “ plastic swaddler ” . All three were found to be equally effective . Overall , 38 % ( 114/298 ) of the infants had temperatures < 36 ° C at 2 h and 18 % ( 41/231 ) at 24 h ( when none was < 35 ° C ) BACKGROUND A previous trial in Nepal showed that supplementation with vitamin A or its precursor ( betacarotene ) in women of reproductive age reduced pregnancy-related mortality by 44 % ( 95 % CI 16 - 63 ) . We assessed the effect of vitamin A supplementation in women in Ghana . METHODS ObaapaVitA was a cluster-r and omised , double-blind , placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana . The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters . All women of reproductive age ( 15 - 45 years ) who gave informed consent and who planned to remain in the area for at least 3 months were recruited . Participants were r and omly assigned by cluster of residence to receive a vitamin A supplement ( 25 000 IU retinol equivalents ) or placebo capsule orally once every week . R and omisation was blocked and based on an independent , computer-generated list of numbers , with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo . Capsules were distributed during home visits undertaken every 4 weeks , when data were gathered on pregnancies , births , and deaths . Primary outcomes were pregnancy-related mortality and all-cause female mortality . Cause of death was established by verbal post mortems . Analysis was by intention to treat ( ITT ) with r and om-effects regression to account for the cluster-r and omised design . Adverse events were synonymous with the trial outcomes . This trial is registered with Clinical Trials.gov , number NCT00211341 . FINDINGS 544 clusters ( 104 484 women ) were r and omly assigned to vitamin A supplementation and 542 clusters ( 103 297 women ) were assigned to placebo . The main reason for participant drop out was migration out of the study area . In the ITT analysis , there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group ( 348 deaths per 100 000 pregnancies ) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group ( 377 per 100 000 pregnancies ) ; adjusted odds ratio 0.92 , 95 % CI 0.73 - 1.17 ; p=0.51 . 1326 women died in 292 560 woman-years in the vitamin A supplementation group ( 453 deaths per 100 000 years ) compared with 1298 deaths in 289 310 woman-years in the placebo group ( 449 per 100 000 years ) ; adjusted rate ratio 1.01 , 0.93 - 1.09 ; p=0.85 . INTERPRETATION The body of evidence , although limited , does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies . FUNDING UK Department for International Development , and USAID A r and omized open-label trial , including 834 pregnant women , examined efficacy and recorded adverse events of ivermectin ( ivc ) and albendazole ( alb ) alone and combined ( comb ) on soil-transmitted helminth infections ( STHs ) in the second trimester of pregnancy . One abortion occurred in the alb group and 10 stillbirths ( 1 , 5 , 3 , and 1 ) in the ivc , alb , comb , and the reference group ( ref ) with no STHs , respectively . Two babies were born with congenital abnormalities ( 1 [ ivc ] and 1 [ ref ] ) . The prevalence of anemia at first antenatal care ( ANC ) visit was 20.6 % ( 23.7 % [ ivc ] , 21.1 % [ alb ] , 22.2 % [ comb ] , and 16.1 % [ ref ] ) . Anemia was reduced to 8.5 % at 36 weeks of gestation with 10.9 % ( ivc ) , 11.5 % ( alb ) , 7.7 % ( comb ) , and 6.9 % ( ref ) . Hookworm cure rates were 29.4 % ( ivc ) , 95.5 % ( alb ) , and 92.6 % ( comb ) . No severe adverse events were reported by the women after the administration of ivc , alb , or comb during the second trimester of pregnancy , but long-term pharmacovigillance is needed to assess safety of ivc , alb , or comb in pregnancy OBJECTIVE To assess the effect on birthweight of antenatal mebendazole plus iron vs. placebo plus iron in a highly hookworm-endemic area . METHODS Double-blind , r and omized controlled trial set in rural and peri-urban communities in the Peruvian Amazon region . A total of 1042 second trimester pregnant women between the ages of 18 and 44 years were recruited from April to November 2003 , and followed to July 2004 . Women were r and omly assigned to receive either mebendazole ( 500 mg single dose ) plus iron supplements ( 60 mg elemental iron daily ) or placebo plus iron supplements . The primary outcome was mean infant birthweight and secondary measures included proportion of low birthweight babies and maternal anaemia . RESULTS The prevalence of hookworm infection was 47.5 % . There were no differences between intervention groups in mean birthweight ( 3104 g vs. 3090 g , P = 0.629 ) , proportion of low birthweight ( < 2500 g ; 8.1%vs . 8.7 % , P = 0.755 ) or maternal anaemia in the third trimester [ 33.0 % ( 158/479 ) vs. 32.3 % ( 152/471 ) , P = 0.815 ] . However , the proportion of very low birthweight ( < 1500 g ) was significantly lower in the mebendazole group [ 0 % ( 0/479 ) vs. 1.5 % ( 7/471 ) , P = 0.007 ] . CONCLUSIONS This trial provides additional evidence for the use of anthelmintics , over and above iron supplementation , within antenatal care programmes in hookworm-endemic areas . Benefits of de-worming may be higher in countries not having an antenatal iron supplementation programme or where intensity of hookworm infections is higher OBJECTIVE Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome . We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1 . DESIGN AND METHODS In Durban , South Africa 728 pregnant HIV infected women received either vitamin A ( 368 ) or placebo ( 360 ) in a r and omized , double-blind trial . The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery . HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis . Results are reported on mother-to-child transmission rates up to 3 months of age . RESULTS There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [ 20.3 % ; 95 % confidence interval ( CI ) , 15.7 - 24.9 ] and placebo groups ( 22.3 % ; 95 % CI , 17.5 - 27.1 ) , nor were there differences in foetal or infant mortality rates between the two groups . Women receiving vitamin A supplement were , however , less likely to have a preterm delivery ( 11.4 % in the vitamin A and 17.4 % in the placebo group ; P = 0.03 ) and among the 80 preterm deliveries , those assigned to the vitamin A group were less likely to be infected ( 17.9 % ; 95 % CI , 3.5 - 32.2 ) than those assigned to the placebo group ( 33.8 % ; 95 % CI , 19.8 - 47.8 ) . CONCLUSION Vitamin A supplementation , a low-cost intervention , does not appear to be effective in reducing overall mother-to-child transmission of HIV ; however , its potential for reducing the incidence of preterm births , and the risk of mother-to-child transmission of HIV in these infants needs further investigation |
11,223 | 17,784,966 | Conclusion In general , therapeutic hypothermia seems to have a beneficial effect on the outcome of term neonates with moderate to severe hypoxic ischemic encephalopathy . | Background The objective of this study was to systematic ally review r and omized trials assessing therapeutic hypothermia as a treatment for term neonates with hypoxic ischemic encephalopathy . | Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury , but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth . This study reports a multicenter , r and omized , controlled , pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event . The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers , and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vinel and tests between normothermic and hypothermic groups . Thirty-two hypothermic and 33 normothermic neonates were enrolled . The entry criteria selected a severely affected group of neonates , with 77 % Sarnat stage III . Ten hypothermia ( 10/32 , 31 % ) and 14 normothermia ( 14/33 , 42 % ) patients expired . Controlling for treatment group , outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers ( odds ratio 10.7 , 95 % confidence interval 1.3 - 90 ) . Severely abnormal motor scores ( Psychomotor Development Index < 70 ) were recorded in 64 % of normothermia patients and in 24 % of hypothermia patients . The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group ( 52 % ) than the normothermia group ( 84 % ) ( P = 0.019 ) . Although these results need to be vali date d in a large clinical trial , this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality . Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials OBJECTIVE To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS Twenty-six term infants with Apgar < or=6 at 5 minutes or cord/first arterial pH < 7.1 , plus evidence of encephalopathy , were studied . After parental consent had been obtained , 13 infants received selective head cooling with the rectal temperature maintained at 35.0 degrees C in 6 infants and at 34.5 degrees C in 7 infants . The remaining 13 infants were normothermic . Cooling was achieved by circulating water at 10 degrees C through a cap placed around the head . Rectal , fontanelle , and nasopharyngeal temperatures were monitored . RESULTS One cooled infant died 2 days after rewarming , and 3 control infants died . Seizures occurred in 9 (69%)of 13 cooled infants and 5 ( 38 % ) of 13 control infants . Respiratory support within the first 72 hours of life was required in 10 of 13 infants in both the cooled and control groups . Three cooled infants and 1 control infant received nitric oxide for persistent pulmonary hypertension . During the same interval , 6 of the cooled infants and 4 of the control infants had episodes in which their blood pressure fell to < 40 mm Hg ; in 2 infants in each group , the lowest blood pressure was below 35 mm Hg . No requirement for volume expansion or increased inotropic support was seen in any infant during stepwise rewarming . All of the cooled infants demonstrated a fall in heart rate during cooling , but the rate was < 80/min in only 2 cases and no infant had a rate < 70/min . No infant demonstrated an abnormal rhythm or was clinical ly compromised by the change in heart rate . One infant cooled to a rectal temperature of 34.5 degrees C had a prolonged QT interval of 570 ms associated with a heart rate of 85/min on electrocardiogram aged 34 hours . This returned to normal after rewarming . Platelet counts below 150 x 10(9)/L , hypoglycemia below 2.6 mmol/L , and highest creatinine were not statistically different between cooled and control infants . Positive precooling blood cultures were found in 1 cooled and 1 control infant . The mean cap water input temperature used during cooling was 10 + /- 1 degrees C. During active cooling , the mean difference between rectal and nasopharyngeal temperature was 1.4 degrees C in the infants who were not receiving respiratory support , but this gradient could not be measured in those who were receiving respiratory support that involved delivery of warmed gases to the nasopharynx . CONCLUSIONS This study suggests that selective head cooling combined with mild systemic hypothermia of 34.4 degrees C or 35.0 degrees C is a stable , well-tolerated method of reducing cerebral temperature in term newborn infants after perinatal asphyxia OBJECTIVE . The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy . METHODS . A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings , assigned r and omly to head cooling for 72 hours , starting within 6 hours after birth ( with the rectal temperature maintained at 34.5 ± 0.5 ° C ) , or conventional care , were studied . Death or severe disability at 18 months of age was assessed in a multicenter , r and omized , controlled study ( the CoolCap trial ) . RESULTS . Treatment , lower encephalopathy grade , lower birth weight , greater amplitude-integrated electroencephalographic amplitude , absence of seizures , and higher Apgar score , but not gender or gestational age , were associated significantly with better outcomes . In a multivariate analysis , each of the individually predictive factors except for Apgar score remained predictive . There was a significant interaction between treatment and birth weight , categorized as ≥25th or < 25th percentile for term , such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling . For larger infants , the number needed to treat was 3.8 . Pyrexia ( ≥38 ° C ) in control infants was associated with adverse outcomes . Although there was a small correlation with birth weight , the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy . CONCLUSIONS . Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy . The protective effect of hypothermia was greater in larger infants Hypoxic-ischemic encephalopathy ( HIE ) remains one of the most important neurologic complications in the newborn . Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage . Furthermore , recent data have suggested that platelet-activating factor ( PAF ) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury . The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia . In addition , we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid ( CSF ) after hypoxic-ischemic brain injury . The group of asphyxiated infants ( Group 1 ) consisted of 21 full-term ( gestational age > 37 weeks ) . These infants were r and omized and divided into either a st and ard therapy group ( Group 1a ; n=10 ) or cooling group ( Group 1b ; n=11 ) . Head cooling combined with minimal hypothermia ( rectal temperature 36.5 - 36 degrees C ) was started as soon as practicable after birth . The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h . The control group ( Group 2 ) consisted of seven full-term infants and none of these infants showed any sign of asphyxia . To measure PAF concentration in CSF , CSF with lumbar puncture was collected into tubes immediately before the cooling ( 1 - 3h after birth ) and again after 36h . We had no evidence of severe adverse events related to hypothermia . In Group 1a , two infants died after 72h of life ; however , all newborn infants in Group 1b survived . Convulsion required treatment in three infants of st and ard therapy group ( 1a ) ; none of the infants in Group 1b had clinical seizure activity . Abnormal EEG patterns were found in four infants of Group 1a ; no EEG abnormalities were noted in Group 1b ( P<0.05 ) . On admission ( before cooling ) , PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control ( P<0.001 ) . Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups ( Group 1a vs. 1b ) ( P>0.05 ) . Obtained PAF level in CSF after 36h , showed a profound decline in cooling group of infants compared to Group 1a infants ( P<0.01 ) . In conclusion , the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging . Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants School performance testing was completed at 8 years of age on 145 children who had had neonatal encephalopathy associated with birth asphyxia as term infants and on a comparison peer group of 155 children . The prospect ively identified clinical categories of encephalopathy for the neonates were 56 mild ( hyperalertness , hyperexcitability ) , 84 moderate ( lethargy , hypotonia , suppressed primitive reflexes ) , and 5 severe ( stupor , flaccidity , absent primitive reflexes ) . The mortality rate to 8 years of age was 13 % . The incidence of impairment , which included cerebral palsy , blindness , cognitive delay , convulsive disorder , and severe hearing loss , was 16 % among those assessed at 8 years ( 75 % of survivors ) . Intellectual , visual-motor integration , and receptive vocabulary scores , as well as reading , spelling , and arithmetic grade levels for those with moderate or severe encephalopathy , were significantly below ( p less than 0.01 ) those in the mild encephalopathy or peer comparison groups . Predictors of reading performance for the study group included category of encephalopathy , birth weight for gestational age , native language , and mother 's educational level ( multiple R = 0.58 ) . Nonimpaired survivors of moderate encephalopathy were more likely to be more than one grade level delayed than were children from the peer group ( reading 35 % vs 15 % , spelling 18 % vs 8 % , arithmetic 20 % vs 12 % , p less than 0.01 ) . Thus children who had moderate and severe neonatal encephalopathy are at risk for physical and mental impairment and reduced school performance . Children with mild encephalopathy had school performance scores similar to those of their peers BACKGROUND Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia . We did a multicentre r and omised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy . METHODS 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography ( aEEG ) were r and omly assigned to either head cooling for 72 h , within 6 h of birth , with rectal temperature maintained at 34 - 35 degrees C ( n=116 ) , or conventional care ( n=118 ) . Primary outcome was death or severe disability at 18 months . Analysis was by intention to treat . We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before r and omisation -- ie , severe loss of background amplitude , and seizures-- and those with less severe changes . FINDINGS In 16 babies , follow-up data were not available . Thus in 218 infants ( 93 % ) , 73/110 ( 66 % ) allocated conventional care and 59/108 ( 55 % ) assigned head cooling died or had severe disability at 18 months ( odds ratio 0.61 ; 95 % CI 0.34 - 1.09 , p=0.1 ) . After adjustment for the severity of aEEG changes with a logistic regression model , the odds ratio for hypothermia treatment was 0.57 ( 0.32 - 1.01 , p=0.05 ) . No difference was noted in the frequency of clinical ly important complications . Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes ( n=46 , 1.8 ; 0.49 - 6.4 , p=0.51 ) , but was beneficial in infants with less severe aEEG changes ( n=172 , 0.42 ; 0.22 - 0.80 , p=0.009 ) . INTERPRETATION These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy , it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes BACKGROUND Hypothermia is protective against brain injury after asphyxiation in animal models . However , the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain . METHODS We conducted a r and omized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy . Infants were r and omly assigned to usual care ( control group ) or whole-body cooling to an esophageal temperature of 33.5 degrees C for 72 hours , followed by slow rewarming ( hypothermia group ) . Neurodevelopmental outcome was assessed at 18 to 22 months of age . The primary outcome was a combined end point of death or moderate or severe disability . RESULTS Of 239 eligible infants , 102 were assigned to the hypothermia group and 106 to the control group . Adverse events were similar in the two groups during the 72 hours of cooling . Primary outcome data were available for 205 infants . Death or moderate or severe disability occurred in 45 of 102 infants ( 44 percent ) in the hypothermia group and 64 of 103 infants ( 62 percent ) in the control group ( risk ratio , 0.72 ; 95 percent confidence interval , 0.54 to 0.95 ; P=0.01 ) . Twenty-four infants ( 24 percent ) in the hypothermia group and 38 ( 37 percent ) in the control group died ( risk ratio , 0.68 ; 95 percent confidence interval , 0.44 to 1.05 ; P=0.08 ) . There was no increase in major disability among survivors ; the rate of cerebral palsy was 15 of 77 ( 19 percent ) in the hypothermia group as compared with 19 of 64 ( 30 percent ) in the control group ( risk ratio , 0.68 ; 95 percent confidence interval , 0.38 to 1.22 ; P=0.20 ) . CONCLUSIONS Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy Aims . To determine the practicality and safety of head cooling with mild or minimal systemic hypothermia in term neonates with moderate to severe hypoxic-ischemic encephalopathy . Methods . Study group infants ≥37 weeks ' gestation , who had an umbilical artery pH ≤7.09 or Apgars ≤6 at 5 minutes , plus evidence of encephalopathy . Infants with major congenital abnormalities were excluded . Trial Design . Infants were r and omized to either no cooling ( controls ; rectal temperature = 37.0 ± 0.2 ° C , n = 10 ) or sequentially , either minimal systemic cooling ( rectal temperature = 36.3 ± 0.2 ° C , n = 6 ) or mild systemic cooling ( rectal temperature = 35.7 ± 0.2 ° C , n = 6 ) . Head cooling was accomplished by circulating water at 10 ° C through a coil of tubing wrapped around the head for up to 72 hours . All infants were warmed by servo-controlled overhead heaters to maintain the allocated rectal temperature . The rectal , fontanelle , and nasopharyngeal temperatures were continuously monitored . Results . From January 1996 to October 1997 , 22 term infants were r and omized from 2 to 5 hours after birth . All infants showed a metabolic acidosis at delivery , with similar umbilical artery pH in the control group ( mean ± st and ard deviation , 6.79 ± 0.25 ) , minimal cooling group ( 6.98 ± 0.21 ) , and mild cooling group ( 6.93 ± 0.11 ) , and depressed Apgar scores at 5 minutes in the control group ( 4.5 ± 2 ) , minimal cooling group , ( 4.7 ± 2 ) and mild cooling group ( 6.0 ± 1 ) . In the mild-cooled infants , the nasopharyngeal temperature was 34.5 ° C during cooling , 1.2 ° C lower than the rectal temperature . This gradient narrowed to 0.5 ° C after cooling was stopped . No adverse effects because of cooling were observed . No infants developed cardiac arrhythmias , hypotension , or bradycardia during cooling . Thrombocytopenia occurred in 2 out of 10 controls , 2 out of 6 minimal cooling infants , and 1 out of 6 mild cooling infants . Hypoglycemia ( glucose < 2.6 mM ) was seen on at least one occasion in 2 out of 10 controls , 4 out of 6 minimal cooling infants , and 1 out of 6 mild cooling infants . Acute renal failure occurred in all infants . The metabolic acidosis present in all infants at the time of enrollment into the study progressively resolved despite cooling , even in the mild hypothermia group . Conclusions . Mild selective head cooling combined with mild systemic hypothermia in term newborn infants after perinatal asphyxia is a safe and convenient method of quickly reducing cerebral temperature with an increased gradient between the surface of the scalp and core temperature . The safety of mild hypothermia with selective head cooling is in contrast with the historical evidence of adverse effects with greater depths of whole-body hypothermia . This safety study and the strong experimental evidence for improved cerebral outcome justify a multicenter trial of selective head cooling for neonatal encephalopathy in term infants Hypoxic-ischemic injury may cause multisystem organ damage with significant aberrations in clotting , renal , and cardiac functions . Systemic hypothermia may aggravate these medical conditions , such as bradycardia and increased clotting times , and very little safety data in neonatal hypoxic-ischemic injury is available . This study reports a multicenter , r and omized , controlled pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in infants with neonatal encephalopathy instituted within 6 hours of birth or hypoxic-ischemic event . The best outcome measures of safety were determined , comparing rates of adverse events between normothermia and hypothermia groups . A total of 32 hypothermia and 33 normothermia neonates were enrolled in seven centers . Adverse events and serious adverse effects were collected by the study team during the hospital admission , monitored by an independent study monitor , and reported to Institutional Review Boards and the Data and Safety Monitoring Committee . The following adverse events were observed significantly more commonly in the hypothermia group : more frequent bradycardia and lower heart rates during the period of hypothermia , longer dependence on pressors , higher prothrombin times , and lower platelet counts with more patients requiring plasma and platelet transfusions . Seizures as an adverse event were more common in the hypothermia group . These observed side effects of 48 hours of moderate systemic hypothermia were of mild to moderate severity and manageable with minor interventions Ninety-five infants of 37 weeks ' gestation or greater with evidence of hypoxic-ischemic encephalopathy following perinatal asphyxia were prospect ively identified in the neonatal period . The degree of encephalopathy was grade d the staging system of Sarnat and Sarnat . Six infants died , 78 infants were sequentially followed in the Neonatal Follow-up Clinic , and in five additional infants , follow-up information was available . The mean duration of follow-up was 19.3 months . Fifty-eight ( 65 % ) of the 89 infants followed were normal or mildly h and icapped , six ( 7 % ) died , and the remainder had significant h and icap . There was no significant relationship between any of over 100 obstetrical antepartum or intrapartum variables and outcome . Infants with five-minute Apgar scores of 0 to 3 , seizures within the first day of life , Stage II or III encephalopathy , or a suppressed electroencephalogram had a significantly greater incidence of severe h and icap or death . In addition , although there were fewer females , they had a significantly greater incidence of h and icap . There appeared to be an improved outcome in the last two years ( 1977 - 1978 ) compared to the first two years ( 1975 - 1976 ) , suggesting that improved recognition and neonatal management may lead to a decrease in significant sequelae OBJECTIVES To determine the neurodevelopmental outcome of infants treated with head cooling with systemic hypothermia after hypoxic-ischemic encephalopathy . STUDY DESIGN Infants > /=37 weeks ' gestation , who had an umbilical artery pH < /=7.09 or Apgar score < /=6 at 5 minutes , plus clinical encephalopathy . Infants with major congenital abnormalities were excluded . TRIAL DESIGN Infants were allocated to either no cooling ( rectal temperature = 37.0 + /- 0.2 degrees C , n = 15 ) , or , sequentially , to head cooling accompanied by different levels of systemic hypothermia , including minimal cooling , rectal temperature 36.5 degrees C to 36 degrees C ( n = 6 ) , and mild cooling , to either 35.9 degrees C to 35.5 degrees C ( n = 6 ) , 35 + /- 0.5 degrees C ( n = 6 ) or 34.5 + /- 0.5 degrees C ( n = 7 ) . Head cooling was accomplished by circulating cooled water through a coil of tubing wrapped around the head for up to 72 hours . Survivors were followed up with regular neurologic examination by a neonatologist until 18 months of age , then with blinded developmental testing using the revised Bayley Scales . RESULTS A total of 40 term infants were enrolled from 2 to 5 hours after birth . The control and the cooled groups were not significantly different for gestation , birth weight , Apgar score , and initial pH. There were 6 early neonatal deaths ( 3 normothermic and 3 cooled ) , and 1 death in infancy associated with severe spastic cerebral palsy in a normothermic infant . Six normothermic , 1 minimally cooled , and 4 mildly cooled infants had early stage 1 encephalopathy ; all but 1 had a good outcome . Among infants with early stage 2 or 3 encephalopathy , an adverse outcome was found in 4 of 9 normothermic infants ( 44 % ) and 4 of 5 minimally cooled infants ( 80 % ) , whereas in the combined mildly cooled groups , an adverse outcome was found in 4 of 15 infants ( 26 % , odds ratio 0.46 [ 0.08 , 2.56 ] vs normothermia ) . CONCLUSIONS The present study supports the safety of hypothermia , with no evidence of late adverse effects in any infant . Among infants with moderate to severe encephalopathy at enrollment , there was a tendency toward better outcome . These results emphasize the relatively wide range of outcomes using purely clinical criteria for enrollment . Therapeutic hypothermia should not be used outside of stringent , multicenter trials OBJECTIVE To study the effects of hypothermia on cardiac function in neonates after birth asphyxia . METHODS Fifty term newborns with Apgar score < 5 at 5 minutes were r and omly divided into no cooling group ( normothermia group , NG ; rectal temperature = 36.5 degrees C + /- 0.5 degrees C , n = 27 ) and cooling group ( hypothermia group , HG ; rectal temperature = 34.5 degrees C + /- 0.3 degrees C , nasopharyngeal temperature = 34.0 degrees C + /- 0.5 degrees C , n = 23 ) . The selective head cooling was applied to maintain nasopharyngeal temperature at 34 degrees C for 72 h in hypothermia group . Systolic and diastolic function was detected at the end of treatment by echocardiogram . RESULTS ( 1 ) The heart rate was obviously decreased during the hypothermia treatment , and there was a significant difference between HG and NG [ ( 103 + /- 15 ) bpm vs. ( 126 + /- 14 ) bpm , P < 0.05 ] . No cardiac arrhythmia and hypotension were found in all neonates . ( 2 ) There were no significant differences on the ejection fraction , stroke volume and cardiac output of left ventricle between the two groups ( P > 0.05 ) . No significant difference was found in the numbers of left and right ventricular diastolic dysfunction , pulmonary hypertension between the two groups ( P > 0.05 ) . ( 3 ) The level of cardiac troponin T ( cTnT ) in plasma was ( 0.47 + /- 0.15 ) ng/ml in HG , and ( 0.35 + /- 0.21 ) ng/ml in NG , and there was no significant difference between the two groups ( P > 0.05 ) . CONCLUSION No significant cardiac dysfunction complication caused by the hypothermia treatment was found in term neonates after birth asphyxia Hypothermia has been proposed as a neuroprotective strategy . However , short-term cooling after hypoxia-ischemia is effective only if started immediately during resuscitation . The aim of this study was to determine whether prolonged head cooling , delayed into the late postinsult period , improves outcome from severe ischemia . Unanesthetized near term fetal sheep were subject to 30 min of cerebral ischemia . 90 min later they were r and omized to either cooling ( n = 9 ) or sham cooling ( n = 7 ) for 72 h. Intrauterine cooling was induced by a coil around the fetal head , leading initially to a fall in extradural temperature of 5 - 10 degrees C , and a fall in esophageal temperature of 1.5 - 3 degrees C. Cooling was associated with mild transient systemic metabolic effects , but not with hypotension or altered fetal heart rate . Cerebral cooling reduced secondary cortical cytotoxic edema ( P < 0.001 ) . After 5 d of recovery there was greater residual electroencephalogram activity ( -5.2+/-1.6 vs. -15.5+/-1.5 dB , P < 0.001 ) and a dramatic reduction in the extent of cortical infa rct ion and neuronal loss in all regions assessed ( e.g. , 40 vs. 99 % in the parasagittal cortex , P < 0.001 ) . Selective head cooling , maintained throughout the secondary phase of injury , is noninvasive and safe and shows potential for improving neonatal outcome after perinatal asphyxia OBJECTIVE Modest reduction in brain temperature is a promising therapy to reduce brain damage after neonatal encephalopathy as a result of acute perinatal asphyxia . The efficacy of modest hypothermia may in part be dependent on the stability of the desired brain temperature . The objective of this study was 1 ) to evaluate in newborn animals a commercially available cooling system ( Blanketrol II Hyperthermia-Hypothermia system ) to control brain temperature during whole-body hypothermia and 2 ) to use the results of the animal experiments to perform a pilot study evaluating the feasibility of whole-body hypothermia as a neuroprotective therapy for newborns with encephalopathy at birth . METHODS In the animal investigation , 3 miniature swine were instrumented and ventilated , and temperature probes were placed in the esophagus and the brain ( 1 cm and 2 cm beneath the parietal cortical surface and the dura ) . Body cooling was achieved using the automatic control mode ( servo ) of the cooling system . In the human investigation , 19 term infants with moderate or severe encephalopathy were r and omized to either normothermia ( n = 10 ) or hypothermia ( n = 9 ) within 6 hours of birth . Whole-body hypothermia was achieved using the hyperthermia-hypothermia cooling system with servo control of esophageal temperature to 34.5 degrees C for 72 hours followed by slow rewarming . RESULTS In the animal investigation , body cooling with the animal lying on a single blanket result ed in rapid cooling of the body within 90 minutes . Repetitive cyclical swings in esophageal temperature of 1.7 + /- 0.2 degrees C ( mean + /- st and ard deviation ) around the set point of 33.5 degrees C were reduced to 0.7 + /- 0.2 degrees C when a second , larger blanket was attached and suspended . Esophageal temperature was a good marker of deep brain temperature ( esophageal to 2-cm brain difference : 0.1 + /- 0.3 degrees C ) . In the human investigation , the infants were r and omized at 4.1 + /- 1.3 hours ( mean + /- st and ard deviation ) after birth . Age at r and omization was similar in the 2 groups . Cooling was initiated at an average age of 5.3 hours . Target temperature of 34.5 degrees C was achieved within 30 minutes and remained constant throughout the intervention period . Heart rate decreased to 108 + /- 14 beats per minute ( bpm ) at 60 minutes and remained between 115 and 130 bpm for the duration of cooling compared with 130 to 145 bpm in the normothermia group . Blood pressure was similar in the 2 groups . No adverse events occurred during 72 hours of cooling . The mortality rate and frequency of persistent pulmonary hypertension , renal failure , hepatic dysfunction , and need for pressor support were similar in both groups . CONCLUSIONS Animal studies showed that a simple modification of a commercially available cooling system ( 2 blankets attached , subject lying on 1 and the second hanging freely ) results in stable core body and brain temperature when used in the automatic control mode . The pilot study in term infants with encephalopathy using this cooling system demonstrates feasibility of initiating whole-body hypothermia at < 6 hours of age to a constant esophageal temperature using servo control and provides no evidence that hypothermia involved greater hazard than benefit Objective : The objective of this study was to determine the efficacy of mild hypothermia via selective head cooling as a neuroprotective therapy in term infants with perinatal asphyxia . Study design : Full-term newborns who had 5 min Apgar scores < 6 , first arterial blood gas pH<7.10 or BD>15 mEq/l , and with the clinical signs of encephalopathy were enrolled within 6 h after birth . Patients were r and omized to receive mild hypothermia treatment via selective head cooling for a total of 72 h or receive routine treatment as a control . Brain hypoxic-ischemic injury was quantified based on the head computed tomographic scan ( CT scan ) at postnatal age 5–7 days and a Neonatal Behavioral Neurological Assessment ( NBNA ) score at 7–10 days of life . Results : A total of 58 patients ( 30 hypothermia , 28 control ) completed the study . Hypothermia was well tolerated in this study and attenuated the hypoxic-ischemic brain injury due to perinatal asphyxia . Head CT scan demonstrated moderate to severe hypoxic-ischemic changes in only 4/30 cases from the hypothermic group . In contrast , 18/28 cases in the control group showed moderate to severe hypoxic-ischemic changes ( χ 2=15.97 , P<0.01 ) . Brain hypothermia also significantly improved the NBNA score ( 32±2 in the hypothermic group vs 28±3 in the control group , P<0.01 ) . Conclusions : Our results suggest that selective head cooling may be used as a neuroprotective therapy in term neonates with perinatal asphyxia . A long-term follow-up study is needed to further vali date the results of this study |
11,224 | 23,223,596 | Treatment of addiction during HCV therapy results in higher treatment completion .
Our pooled SVR rate is similar to that obtained in registration trials in the general population . | BACKGROUND Hepatitis C virus (HCV)-infected drug users ( DUs ) have largely been excluded from HCV care .
We conducted a systematic review and meta- analysis of the literature on treatment completion and sustained virologic response ( SVR ) rates in DUs .
We assessed the effects of different treatment approaches and services to promote HCV care among DUs as well as demographic and viral characteristics . | BACKGROUND In developed countries hepatitis C is prevalently transmitted by intravenous drug users ( IDUs ) . The problems associated with management of HCV hepatitis in these patients have , in the past , discouraged treatment . AIM To evaluate efficacy , safety and tolerability of a st and ard Peginterferon ( Peg-IFN ) alpha-2b or alpha-2a plus Ribavirin treatment in IDUs who were receiving methadone or buprenorphine . METHODS A multi-centre prospect i ve observational study performed from September 2003 to September 2006 in Central Italy ( Umbria and Marches regions ) . A shared care model of HCV management was used which integrated a multidimensional , multidisciplinary approach . RESULTS Sixty-five subjects were evaluated and 52 satisfied inclusion criteria . Forty-five completed treatment ( 25 with Peg-IFN alpha-2b , 20 with Peg-IFN alpha-2a ) , a total of 37 showed a biochemical/virological response at the end of treatment ( ITT 71.1 % ) , 26 had a sustained virological response ( ITT 50 % ; 38.4 % of cases genotype 1 - 4 , 61.6 % genotype 3 - 2 ) . CONCLUSIONS The results indicate that patients on maintenance treatment with methadone/buprenorphine can be treated for HCV . The success rate was fairly good ; tolerability and side effects were similar to those reported in non-IDU patients . Close cooperation with specialists in drug addiction and psychiatrists is however essential for success AIM To evaluate the effect of a multi-disciplinary st and ardized management model on the efficacy of pegylated (Peg)-interferon alpha-2b plus ribavirin treatment of chronic hepatitis C in drug addicts undergoing substitutive or antagonist therapy . DESIGN Observational prospect i ve multi-centre study . SETTING Six clinical infectious disease centres in collaboration with 11 drug dependency units ( DDU ) in five Italian regions . PARTICIPANTS Intravenous drug users affected by chronic hepatitis C engaged in detoxification programmes . METHODS Application of a multi-disciplinary st and ardized management model for HCV treatment involving DDU operators , psychologists or psychiatrists and infectious disease specialists . MEASUREMENTS Very early , early , end-of-treatment and sustained virological response to Peg-interferon alpha-2b plus ribavirin . FINDINGS Fifty-three subjects were studied [ 43.4 % with hepatitis C virus ( HCV ) genotypes 1 or 4 ] . Intent-to-treat analysis showed an end-of-treatment virological response in 58.5 % of patients ( 39.1 % genotypes 1 or 4 ; 73.4 % genotype 3 ) and a sustained virological response in 54.7 % ( 34.8 % genotypes 1 or 4 ; 70.0 % genotype 3 ) . There were 19 ( 35.8 % ) dropouts and three ( 5.7 % ) non-responders : one genotype 1 and two genotype 4 . Two ( 3.8 % ) patients relapsed : genotypes 1 and 3 . On-treatment analysis showed negative HCV-RNA in 40 ( 93.1 % ) of 43 subjects who completed the first 12 treatment weeks and in 35 who completed the first 24 treatment weeks . All subjects with an end-of-treatment response , except one with genotype 3 infection , had a sustained response . CONCLUSIONS Our data show that antiviral treatment in the context of a multi-disciplinary st and ardized management model helps many HCV-positive drug addicts achieve a good virological response BACKGROUND / AIMS Treatment with interferon-alpha ( IFN-alpha ) may eradicate HCV in most acute hepatitis C patients , thus preventing chronic hepatitis and avoiding less efficacious combination therapy . METHODS In a prospect i ve study , we evaluated the impact of barriers to successful start and completion of treatment of acute and subacute ( < 12 months from infection ) hepatitis C with pegylated IFN-alpha2b , 1.5 microg/kg , QW , for 24 weeks . RESULTS Out of 27 patients ( 22 were active intravenous drug users [ IVDU ] ) , 5 cleared HCV spontaneously . Antiviral treatment was indicated in 22 patients : six refused therapy for fear of side effects , whereas two others were lost to observation . Eight patients completed the treatment or received > 80 % of the scheduled drug : seven ( 88 % ) were sustained virological responders 24 weeks after the end of treatment . Six patients ( all IVDU ) stopped prematurely due to side effects : only one had a sustained virological response . Based on an intent-to-treat analysis , and considering all 14 patients in whom at least one dose of drug was administered , only 8 ( 57 % ) became sustained virological responders . CONCLUSIONS Treatment of acute hepatitis C with pegylated IFN-alpha is highly beneficial , but its effectiveness is affected by a poor rate of acceptance and /or adherence to currently available regimens , especially in IVDU and women BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections Background : Though patients in opiate substitution programs are commonly infected with HCV , due to safety and efficacy concerns , they are rarely treated with interferon and ribavirin . Methods : In a multicenter study , HCV-infected patients in opiate maintenance treatment programs received 180 μg pegylated interferon-alfa-2a once weekly , plus daily ribavirin for 24 weeks ( genotypes 2 , 3 ) , or 48 weeks ( genotypes 1 , 4 ) . Results : Of the 67 patients enrolled , 31 ( 46 % ) had HCV genotypes 1 or 4 , and 36 ( 54 % ) had genotypes 2 or 3 . Intent-to-treat analysis showed end-of-treatment virologic response in 75 % of patients ( 81 % of genotypes 2 or 3 ; 65 % of genotypes 1 or 4 ) , and a sustained virologic response in 61 % of patients ( 72 % of genotypes 2 or 3 ; 48 % of genotypes 1 or 4 ) . Fifteen patients ( 22 % ) did not complete the study , in 5 ( 8 % ) cases because of severe adverse events . Conclusions : Drug users with chronic HCV infection , regularly attending an opiate maintenance program in which close collaboration between hepatologists/internists and addiction specialists is assured , can be treated effectively and safely with pegylated interferon-alfa-2a and ribavirin . Treatment results are very similar to those in other patient groups , and thus therapy should also be considered for this population BACKGROUND A minority of HIV/HCV coinfected patients with opiate addiction undergo HCV treatment . HCV therapy for HCV-monoinfected methadone maintenance ( MM ) recipients is safe and effective . We evaluated treatment efficacy and adherence to pegylated interferon ( pegIFN ) among HIV/HCV coinfected MM recipients . METHODS HCV treatment-naïve , HIV-infected persons 18 - 65 years with chronic HCV genotype 1 on MM were prospect ively enrolled in an HCV treatment study at two HIV clinics . At weekly visits pegIFN alfa-2a injections were directly administered . Daily MM recipients had morning ribavirin delivered with methadone at off-site methadone clinics . Weekly take-home MM recipients took ribavirin unsupervised . Target enrollment was 30 participants . RESULTS During 18 recruitment months , 11 participants were enrolled , 6 of whom received daily methadone . Mean age was 46 , 64 % were female , 5 were Caucasian , 4 Black and 2 Hispanic . At baseline , 82 % had high HCV RNA and 55 % had stage 2 fibrosis or greater . The majority ( 91 % ) were on HAART , and 82 % had undetectable HIV RNA with a median CD4(+ ) of 508cells/μL. All had polysubstance use history , non-substance-based psychiatric diagnoses and were on psychotropic medications pre-enrollment . Two ( 18 % ) participants achieved a Sustained Virologic Response ( SVR ) . Two completed 48 treatment weeks , 5 were withdrawn due to adverse events , 2 dropped out prematurely and 2 had treatment discontinued for virologic non-response . Of on-treatment weeks , adherence to pegIFN was > 99 % . CONCLUSIONS SVR rate was comparable to historic controls for coinfected genotype 1 patients , with optimal pegIFN adherence . Adverse effects often prevented therapy completion in this population BACKGROUND : Adherence to chronic hepatitis C ( CHC ) treatment may be particularly challenging in methadone maintenance patients . We assessed the safety , tolerability , and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC . METHODS : Patients were r and omized 1:1 to direct observed therapy ( DOT ) or self-administration ( SA ) of peginterferon alfa-2a . DOT patients were seen weekly at methadone clinics ; SA patients were seen less frequently , only at investigative sites . Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 1,000/1,200 mg/day ) ; genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 800 mg/day ) . RESULTS : Based on defined efficacy stopping rules , 77 % ( 37/48 ) completed their targeted length of treatment , and 44 % ( 21/48 ) achieved sustained virologic response ( SVR ) . Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9 , respectively , for nonsafety reasons . Over 60 % and 50 % of each group were > 80 % compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin , respectively , and over 60 % with overall treatment duration . SVR rates were 54 % ( 13/24 ) for DOT and 33 % ( 8/24 ) for SA ; 23 % ( 3/13 ) and 38 % ( 6/16 ) , respectively , for genotype 1 and 91 % ( 10/11 ) and 25 % ( 2/8 ) , respectively , for genotypes 2 and 3 . Stepwise logistic regression analysis , showed that DOT ( vs SA ; OR 3.27 , 95 % CI 0.90–11.91 , P= 0.073 ) and Caucasian race ( vs Other ; OR 13.31 , 95 % CI 1.42–124.71 , P= 0.023 ) were predictors of SVR . CONCLUSION : Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were r and omly assigned to treatment and received at least one dose of study medication , consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1000 or 1200 mg , depending on body weight ) , weekly peginterferon alfa-2a plus daily placebo , or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks . RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than of patients who received interferon alfa-2b plus ribavirin ( 56 percent vs. 44 percent , P<0.001 ) or peginterferon alfa-2a alone ( 56 percent vs. 29 percent , P<0.001 ) . The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent , 36 percent , and 21 percent , respectively , for the three regimens . Among patients with HCV genotype 1 and high base-line levels of HCV RNA , the proportions of those with sustained virologic responses were 41 percent , 33 percent , and 13 percent , respectively . The overall safety profiles of the three treatment regimens were similar ; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin . CONCLUSIONS In patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response , as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone To examine rates and predictors of referral for hepatitis C virus ( HCV ) treatment and preliminary treatment outcomes in injecting drug users ( IDUs ) receiving opioid replacement treatment , a prospect i ve clinical audit was undertaken in an inner city Sydney drug dependency treatment practice between December 2002 and November 2005 . The majority of IDUs ( 178/237 ; 75 % ) were HCV antibody positive , of whom 170 were HCV treatment naïve with no absolute treatment contraindications . Among these 170 patients , 121 ( 71 % ) had chronic HCV . Based on risk factors for HCV disease progression , 63 of 121 ( 52 % ) chronic HCV patients were targeted for referral ; these patients were older , had higher alanine aminotransferase levels and longer estimated duration of HCV infection . Of these 63 patients , 43 were referred to a hepatitis treatment clinic , and 27 attended during the audit period . Patients who attended for treatment assessment were more likely to have genotype 2 or 3 ( p<0.001 ) , but socio-behavioural factors were similar . Liver biopsy was performed in 20 patients , with moderate or greater fibrosis in 18 patients . Of 14 patients commenced on pegylated interferon-alpha and ribavirin therapy , one ceased treatment due to non-response , 10 have completed treatment , all with an end-of-treatment ( n=4 ) or sustained virological response ( n=6 ) , and treatment is ongoing in three . The development of HCV treatment referral criteria has allowed prioritisation of patients for referral , potentially halving those that require early assessment . Preliminary HCV treatment outcomes are encouraging and highlight the potential for reducing liver disease burden in this patient population Hepatitis C Virus ( HCV ) infection is treated with peg-interferon & agr;2a or & agr;2b and ribavirin . International studies show that drug user adherence to treatment is 40 % to 60 % and increases if the patient is in addiction treatment . The aim of the Together To Take Care ( TTTC ) study was to achieve better adherence to HCV therapy in r and omly selected drug users , who are considered “ difficult to treat . ” The secondary aim of the TTTC Study Group was to st and ardize a method for a multidisciplinary management of the liver disease in drug users . The TTTC group data were matched with a control group . Adherence : The 93.7 % of patients followed therapy prescribed ; of the patients infected by HCV genotype ( gt ) 3 , all completed therapy as scheduled . For the 48-week treatment group , 66.7 % of patients completed therapy ( 2 of 9 patients stopped treatment for breakthrough ) . Toxicological results : 10 ( 62.5 % ) patients were negative in the toxicological tests ( opiates , cocaine , and alcohol ) . Virological results : 8 of 16 patients were infected by HCV gt 1 , and 8 were infected by gt 3 ; 2 of 16 ( 12.5 % ) patients were human immunodeficiency virus ( HIV ) coinfected ( 1 HCV gt 1a and 1 HCV gt 3 ) . All patients : 11 of 16 ( 68.75 % ) patients were HCV ribonucleic acid undetectable 24 weeks after completing therapy ( sustained virological response , SVR ) . Gt 1 : 4 of 8 ( 50.0 % ) showed SVR . Gt 3 : 7 of 8 ( 87.5 % ) showed SVR . Overall , the HCV gt 3 patients had 87.5 % probability of SVR , whereas gt 1 patients had 50 % probability of SVR ( gt 3/gt 1 patients odds ratio = 7 ) . The results were analyzed by Fisher exact test . Our results show that good healthcare management plays an important role in increasing patients ' adherence to therapy . In the project “ TTTC , ” the patients work with the physicians to take responsibility for their health and acquire self-efficacy and self-awareness , thanks to the special care BACKGROUND In phase 2 trials , telaprevir , a hepatitis C virus ( HCV ) genotype 1 protease inhibitor , in combination with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , has shown improved efficacy , with potential for shortening the duration of treatment in a majority of patients . METHODS In this international , phase 3 , r and omized , double-blind , placebo-controlled trial , we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups : a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks ( T12PR group ) , followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point ; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks ( T8PR group ) , followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria ; or a group receiving placebo with peginterferon-ribavirin for 12 weeks , followed by 36 weeks of peginterferon-ribavirin ( PR group ) . The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment ( sustained virologic response ) . RESULTS Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response ( 75 % and 69 % , respectively , vs. 44 % ; P<0.001 for the comparison of the T12PR or T8PR group with the PR group ) . A total of 58 % of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment . Anemia , gastrointestinal side effects , and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone . The overall rate of discontinuation of the treatment regimen owing to adverse events was 10 % in the T12PR and T8PR groups and 7 % in the PR group . CONCLUSIONS Telaprevir with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment , with only 24 weeks of therapy administered in the majority of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ADVANCE Clinical Trials.gov number , NCT00627926 . ) We examined the feasibility of hepatitis C treatment in patients on opioid maintenance . One hundred patients with chronic hepatitis C , 50 on methadone maintenance , and 50 with no intravenous drug use or opioid maintenance for at least 5 years were prospect ively matched for sex , age , hepatitis C virus ( HCV ) genotype and HCV RNA . The primary end point was undetectable HCV RNA at 24 weeks posttreatment . Treatment with peginterferon alfa-2b ( 1.5 microg/kg per week ) and ribavirin ( 1000 - 1200 mg /day ) was initiated for 24 weeks ( HCV genotype 2 , 3 ) or 48 weeks ( HCV genotype 1 , 4 ) . Within the first 8 weeks of therapy , discontinuation due to noncompliance or patient request was observed in 22 % ( 11/50 ) in the methadone group versus 4 % ( 2/50 ) in the control group ( P = .02 ) . After 8 weeks , there was no significant difference in discontinuation due to noncompliance or patient request ( 4/39 [ 10 % ] vs. 4/48 [ 8 % ] ) . There was no difference in discontinuation of therapy because of viral failure or adverse events ( 10/50 methadone vs. 6/50 control , P = .41 ) . At the end of treatment , 50 % ( 25/50 ) in the methadone group and 76 % ( 38/50 ) in the control group had undetectable HCV RNA ( P = .01 ) . Sustained viral response was 42 % ( 21/50 ) in the methadone group and 56 % ( 28/50 ) in the control group ( P = .16 ) . No serious psychiatric event occurred in either group . In conclusion , peginterferon and ribavirin seem reasonably safe and sufficiently effective in patients on methadone maintenance . Patients discontinuing therapy due to noncompliance or request did so early , thereby limiting the cost of an unsuccessful approach to treatment UNLABELLED We investigated and compared the results of treating the chronic hepatitis C ( HCV ) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha ( pegIFN-alpha ) plus ribavirin . Seventy patients were prospect ively screened for psychiatric disorders . Seventeen patients without psychiatric diseases or drug addiction ( controls ) , 22 patients with psychiatric disorders , 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-alpha plus ribavirin . Sustained virological response ( SVR ) , adherence , and psychiatric side effects ( using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale ) in the groups were compared . An SVR was found in 58.6 % of all patients : 58.8 % of the controls , 50 % of psychiatric patients , 72.2 % of methadone patients , and 53.8 % of former drug users . Methadone-substituted patients and former drug users had significantly higher dropout rates . Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment . However , the controls had lower pretreatment scores , followed by a significant higher increase to maximum scores . A stepwise logistic regression model showed that only genotype , not group ( control , psychiatric , methadone , or former drug abuse ) , type of psychiatric diagnosis ( affective disorder , personality disorder , or schizophrenic disorder ) , depression scores before and during treatment , change in depression score , antidepressive treatment , sex , or liver enzymes before treatment , was associated with SVR . CONCLUSION In an interdisciplinary treatment setting psychiatric diseases and /or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-alpha and ribavirin AIMS To identify predictors of patient retention in methadone maintenance . DESIGN Prospect i ve study . SETTING Methadone maintenance treatment programme newly established in Geneva , Switzerl and . PARTICIPANTS All patients who initiated treatment between February 1991 and January 1995 . MEASUREMENTS Baseline patient characteristics , dose of methadone , year of enrollment and retention in treatment . FINDINGS Overall , 111 patients contributed 164.4 person-years of follow-up . The retention rate was 84 % after 12 months . In multivariate analysis , the risk of dropping out was significantly higher for patients who had been using opioids for < or = 7 years ( relative hazard ( RH ) 3.0 , 95 % confidence interval ( CI ) 1.2 - 7.4 ) , and for patients who had no stable income at baseline ( RH 3.3 , 95 % CI 1.2 - 9.1 ) . Dropouts were less frequent at the highest doses of methadone ( 65 - 110 mg/day , RH 1.0 ) than at middle doses ( 45 - 60 mg/day , RH 2.0 , 95 % CI 0.7 - 5.5 ) but , quite unexpectedly , dropouts were least likely at the lowest doses ( 15 - 40 mg/day , RH 0.5 , 95 % CI 0.1 - 1.8 ) . Dropouts were more likely among patients who enrolled in the first ( RH 6.2 , 95 % CI 2.3 - 16.7 ) and second ( RH 1.9 , 95 % CI 0.6 - 5.6 ) years of the programme , compared with subsequent years ( RH 1.0 ) . CONCLUSIONS Patients who have a long history of drug use and who have a stable income were more likely to stay in methadone maintenance treatment . Independent of patient characteristics , retention improved dramatically in the first years of programme functioning , suggesting that patient retention is a sensitive indicator of programme performance Background : Many physicians are still skeptic to treat opioid dependants , with or without maintenance treatment , for hepatitis C ( HCV ) because of concerns about psychiatric comorbidity , stability and adherence . In Norway , there are about 3,500 patients participating in the restrictive medication-assisted rehabilitation ( LAR ) programs in which all patients are given methadone or buprenorphine maintenance therapy . This study was undertaken to determine whether HCV combination therapy with pegylated interferon α-2a plus ribavirin is feasible , efficient and safe in this patient group . Method : Seventeen patients with HCV genotype 3a were treated for 24 weeks . To optimize compliance , the treatment was given from a department of infectious diseases in cooperation with an LAR center . All injections were given in the LAR center and the patients were given psychosocial support . Results : The compliance was 100 % . All responded to the therapy and 16 ( 94 % ) were sustained responders . Discussion / Conclusion : This study indicates that compliance and treatment outcome of opioid dependants on methadone or buprenorphine maintenance after 24 weeks of HCV treatment corresponds to that for non-dependants if extra support is given . The treatment should be undertaken in collaboration with specialists in addiction medicine , hepatology and infectious diseases Background Injecting drug use is the main risk factor for hepatitis C virus ( HCV ) infection . Secondary ‐care‐based strategies for the management of HCV do not effectively target this vulnerable population BACKGROUND Peginterferon-ribavirin therapy is the current st and ard of care for chronic infection with hepatitis C virus ( HCV ) . The rate of sustained virologic response has been below 50 % in cases of HCV genotype 1 infection . Boceprevir , a potent oral HCV-protease inhibitor , has been evaluated as an additional treatment in phase 1 and phase 2 studies . METHODS We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were r and omly assigned to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( the control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks , and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . Nonblack patients and black patients were enrolled and analyzed separately . RESULTS A total of 938 nonblack and 159 black patients were treated . In the nonblack cohort , a sustained virologic response was achieved in 125 of the 311 patients ( 40 % ) in group 1 , in 211 of the 316 patients ( 67 % ) in group 2 ( P<0.001 ) , and in 213 of the 311 patients ( 68 % ) in group 3 ( P<0.001 ) . In the black cohort , a sustained virologic response was achieved in 12 of the 52 patients ( 23 % ) in group 1 , in 22 of the 52 patients ( 42 % ) in group 2 ( P=0.04 ) , and in 29 of the 55 patients ( 53 % ) in group 3 ( P=0.004 ) . In group 2 , a total of 44 % of patients received peginterferon-ribavirin for 28 weeks . Anemia led to dose reductions in 13 % of controls and 21 % of boceprevir recipients , with discontinuations in 1 % and 2 % , respectively . CONCLUSIONS The addition of boceprevir to st and ard therapy with peginterferon-ribavirin , as compared with st and ard therapy alone , significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection . The rates were similar with 24 weeks and 44 weeks of boceprevir . ( Funded by Schering-Plough [ now Merck ] ; SPRINT-2 Clinical Trials.gov number , NCT00705432 . ) AIMS The aim of this clinical study was to assess virological response at end-of -treatment ( ETR ) , sustained virological ( SVR ) and biochemical response in former drug users with chronic hepatitis C treated with PEG-IFN-alpha and R. PATIENTS Ninety two former drug users ( 21 F , 71 M ) average age 27 years ( 18 to 41 years ) and previously not treated with IFN-alpha and R ( naive patients , pts ) were evaluated for their virological and biochemical response . St and ard treatment regimen of either 24 or 48 weeks was applied in patients with genotype 3 or genotype 1 , respectively . SVR was considered if viral tests ( HCV RNA ) were negative 24 weeks after the end of treatment . RESULTS Overall SVR was attained in 87 ( 95 % ) of 92 treated patients , and therapy failed in 5 pts with genotype 1 . In genotype 1 patients ETR and SVR were 81 % and 86 % , respectively ( p < 0.001 ) . In genotype 3 patients ETR and SVR were 98 % and 100 % , respectively ( p < 0.001 ) . ALT levels decreased significantly after 12 weeks of therapy ( ALT 1.61 vs 0.64 micro/kat/l , p < 0.001 ) and were at normal levels during follow-up . CONCLUSIONS Crucial predictive factors result ing in high SVR were the younger age in combination with low stage of liver fibrosis , relatively short duration of viral infection , high proportion of genotype 3 and excellent adherence of patients to treatment regimen than previously not treated with IFN-alpha and R ( naive patients ) . High proportion of SVR in former drug users has been achieved in patients with genotype 3 ( 100 % ) and genotype 1 ( 86 % ) . The most decisive prognostic factor which favors high therapeutic efficacy appears to be young age and early onset of anti-HCV treatment ( Tab . 3 , Fig. 1 , Ref . 33 ) . Full Text ( Free , PDF ) www.bmj.sk Objective Injection drug users are often excluded from hepatitis C virus ( HCV ) treatment . This study compares sustained virological response , adherence , and quality of life in patients with or without a history of illicit drug use in routine clinical practice . Methods This is a post-hoc analysis of a prospect i ve , observational study conducted in 1860 patients who received peginterferon α-2b/ribavirin combination therapy . Nondrug users ( NDUs ) were defined as patients without a history of drug addiction ; former drug users ( FDUs ) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users ( ADUs ) as patients using illicit drugs or on opioid maintenance therapy . Virological response , adherence , and the health-related quality of life were assessed by the measure of HCV RNA in the serum , self-report and 36-item short-form health survey Question naire , respectively . Results The analyzed population included 1038 ( 56 % ) NDUs , 578 ( 31 % ) FDUs , and 244 ( 13 % ) ADUs . About 85 % of ADUs were on opioid maintenance therapy and 25 % used illicit drugs . Although ADUs had a more chaotic lifestyle and more psychiatric disorders , sustained virological response of ADUs ( 58 % ) did not differ from that of NDUs ( 49 % ) and FDUs ( 51 % ) ( P=0.133 ) . Adherence rates were 39 % in NDUs and FDUs , and 37 % in ADUs ( P=0.883 ) . Health-related quality of life was improved in the three groups after the end of treatment . Conclusion Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients . The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies Despite that the majority of hepatitis C virus ( HCV ) infection occurs among injection drug users ( IDUs ) , little is known about HCV treatment uptake in this group , particularly during recent infection . We evaluated uptake of treatment for recent HCV infection , including associated factors , within a population predominantly made up of IDUs . The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV infection . All participants with detectable HCV RNA at screening were offered HCV treatment , assessed for eligibility and those initiating treatment were identified . Logistic regression analyses were used to identify predictors of HCV treatment uptake . Between June 2004 and February 2008 , 163 were enrolled , with 146 positive for HCV RNA at enrolment . The mean age was 35 years , 77 % ( n=113 ) participants had ever injected illicit drugs and 23 % ( n=34 ) reported having ever received methadone or buprenorphine treatment . The uptake of HCV treatment was 76 % ( 111 of 146 ) among those who were eligible on the basis of positive HCV RNA . Estimated duration of HCV infection ( OR=1.03 per week , 95 % CI=1.00 - 1.06 , P=0.035 ) and log(10 ) HCV RNA ( OR=1.92 per log(10 ) increase , 95 % CI=1.36 - 2.73 , P<0.001 ) were independently associated with treatment uptake whereas injection drug use was not . This study demonstrates that a high uptake of HCV treatment can be achieved among participants with recently acquired HCV infection . Decisions about whether to initiate treatment for recently acquired HCV were mainly driven by clinical factors , rather than factors related to sociodemographics or injecting behaviors Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus ( HCV ) infection . However , very few injection drug users ( IDUs ) have received treatment for this condition given issues of medical or psychiatric co-morbidity , ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy , including regular medical follow-up . With this in mind , we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy . Utilizing the existing infrastructure for the management of addictive disease , we have developed a model of " one-stop shopping " whereby the treatment of addiction , HCV and other medical conditions are fully integrated , with the collaboration of nurses , counsellors , addiction specialists , infectious disease specialists , primary care physicians and research ers . Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment . Patients received therapy with pegylated interferon-alpha2a or -alpha2b , both in combination with ribavirin . All injections were directly observed . Overall , we observed a high uptake of HCV treatment among attendees , with 51 percent either receiving or about to receive therapy . To date , 18 patients have initiated treatment for HCV infection and 12 have completed therapy . Overall , 8/12 ( 67 percent ) subjects achieved an end of treatment response ( genotype 1 , 67 percent ; genotypes 2/3 , 67 percent ) , despite ongoing drug use in 75 percent of patients during treatment . These data demonstrate that with the appropriate programs in place , a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group . Moreover , the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken , result ing in ETRs similar to those reported in r and omized controlled trials The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear . Patients attending a community‐based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy . The first 50 patients to commence HCV therapy and complete at least 6 months follow‐up were prospect ively studied . ETR response ( HCV PCR negative ) was 34/50 ( 68 % ) and SVR 6 months post‐treatment was 31/50 ( 62 % ) . Viral eradication was maintained in those 22 patients that have had 12 months or more post‐treatment follow‐up . Eleven ( 22 % ) patients stopped therapy early due to side effects or poor compliance . Only two patients with an ETR likely reinfected due to unsafe injection practice s. One was re‐treated and achieved an SVR . Of the patients achieving a 6‐month SVR , 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation . 46 % of patients received antidepressant and /or antipsychotic medication during treatment . Conclusion : This study of HCV treatment in a community‐based subcutaneous naltrexone implant clinic found antiviral therapy result ed in a 62 % SVR . This result is comparable to that reported in hospital‐based clinics in non‐IDU patients . The side effect profile and compliance was also similar . HCV antiviral therapy should be offered to this large and currently under treated group . ( HEPATOLOGY 2007;45:111–117 . Introduction Chronic hepatitis C virus infection ( HCV ) is the most common infectious disease among intravenous drug users . Aims To determine and compare compliance rates between two groups of chronic HCV patients from the methadone substitution program of the National Greek Organization Against Drugs treated with either pegylated interferon & agr;-2b/ribavirin or with interferon & agr;-2b/ribavirin during 48 weeks of therapy and 24 weeks of follow-up . Furthermore , to evaluate the efficacy of each treatment modality . Methods Forty-five consecutive methadone maintenance ( MM ) patients ( group A , 36 males , nine females ) were treated with pegylated interferon & agr;-2b ( weight-based dosing 1.5 μg/kg/week ) and ribavirin 1000–1200 mg/day orally . Sixty-five consecutive MM patients ( group B , 52 males , 13 females ) were treated with interferon & agr;-2b ( 6 MIU , three times/week ) and ribavirin with the doses reported above . During the study , all patients were followed up periodically by hepatologists , internists , and psychiatrists . Results Baseline characteristics were similar between the two groups . Thirty-four out of 45 patients ( 75.6 % ) from group A and 31 of 65 patients ( 47.7 % ) from group B completed therapy ( P=0.006 ) . Thirty-two ( 71.1 % ) patients from group A and 27 patients ( 41.5 % ) from group B were followed-up until the end of week 72 ( P=0.004 ) . At the end of the follow-up , sustained virologic response was achieved in 23 of 45 ( 51.1 % ) patients from group A and 21 of 65 patients ( 32.3 % ) from group B ( P=0.075 ) . Conclusion Pegylated interferon & agr;-2b/ribavirin treatment achieved a significantly higher compliance rate than interferon & agr;-2b/ribavirin in MM patients with chronic HCV infection . After 24 weeks of follow-up , response rates were similar for patients who were compliant to treatment for both groups AIMS To evaluate the efficacy , safety and adherence to hepatitis C ( HCV ) therapy in patients attending tertiary hepatitis clinics who are receiving opioid replacement therapy . DESIGN A non-r and omized , open-label study . Participants were treated with pegylated interferon alpha-2a and weight-based ribavirin for 24 weeks ( genotype non-1 , n = 31 ) or 48 weeks ( genotype 1 , n = 22 ) . SETTING Four tertiary hospital hepatitis clinics in Australia . PARTICIPANTS Fifty-three patients with chronic HCV who were receiving opioid replacement therapy . MEASUREMENTS Patients were monitored for virological response , adverse events and adherence . They were also screened for psychiatric illness prior to and throughout the study utilizing two vali date d instruments : the Mini International Neuropsychiatric Interview ( MINI ) and Beck Depression Interview (BDI)-II . FINDINGS The overall sustained virological response ( SVR ) rate was 57 % ( 71 % genotype non-1 versus 36 % genotype 1 ) , and was similar in active injectors ( 63 % ) and non-injectors ( 53 % ) . The psychological profile of patients based on vali date d instruments did not change on therapy . The pattern and frequency of adverse effects were comparable to non-opioid replacement patients . Eighty-five per cent of patients were adherent to therapy by 80/80/80 criteria and only two patients who had an end-of-treatment response relapsed , one of whom was not an active injector . CONCLUSIONS Patients on opioid replacement therapy , even if they continue to inject actively , can achieve comparable sustained virological response rates to other population s with pegylated interferon alpha-2a and ribavirin therapy , suffer no excess rates of adverse effects or psychological complications and have good adherence to therapy |
11,225 | 16,855,966 | There was a lack of high quality evidence about the effectiveness of combinations of social influences and social competence approaches .
There is one rigorous test of the effects of information-giving about smoking . | BACKGROUND Smoking rates in adolescents are rising in some countries .
Helping young people to avoid starting smoking is a widely endorsed goal of public health , but there is uncertainty about how to do this .
Schools provide a route for communicating with a large proportion of young people , and school-based programmes for smoking prevention have been widely developed and evaluated .
OBJECTIVES To review all r and omized controlled trials of behavioural interventions in schools to prevent children ( aged 5 to12 ) and adolescents ( aged 13 to18 ) starting smoking . | This article evaluates the effects and use of adjuncts to a televised smoking cessation program , based on the American Lung Association 's " Freedom From Smoking in 20 Days . " Subjects were r and omized to maintenance and control conditions . The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline . The maintenance condition did not increase cessation at any wave of interviewing , assessed by multiple point or point prevalence of abstinence . Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage . Rates of use of the telephone hotline were low . The newsletters appear to be useful to smokers who are predisposed to use written material OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs A population -based , r and omized universal classroom intervention trial for the prevention of disruptive behavior ( i.e. , attention-deficit/hyperactivity problems , oppositional defiant problems , and conduct problems ) is described . Impact on developmental trajectories in young elementary schoolchildren was studied . Three trajectories were identified in children with high , intermediate , or low levels of problems on all 3 disruptive behaviors at baseline . The intervention had a positive impact on the development of all disruptive behavior problems in children with intermediate levels of these problems at baseline . Effect sizes of mean difference at outcome were medium or small . In children with the highest levels of disruptive behavior at baseline , a positive impact of the intervention was found for conduct problems This study evaluates a youth subject-directed smoking prevention and cessation program titled Breathe Easy ! The program was delivered at two sites and a control group was recruited from two additional sites . Surveys were administered prior to the program and either 1 month or 6 months after completion at the exposure sites . The same survey administration procedure was used as the control . After controlling for invalid responses and including only those that completed both surveys , 251 exposure subjects and 159 control subjects remained for analysis . At sites with 1-month follow-up , no significant difference was noted between intervention and control groups . At the sites with 6-month follow-up , prevalence dropped from 18.7 % to 8.9 % , which is statistically significant , while at the control site prevalence changed from 14.1 % to 9.4 % , which is not significant . Additional outcomes examined in the exposed group showed trends toward smoking cessation and prevention at higher rates than those of the unexposed group BACKGROUND No long-term impact has yet been observed with the use of the social-influences approach to school-based smoking prevention for youth . However , whether this lack of impact is due to method ologic problems with the studies or to the failure of the interventions is unclear . The Hutchinson Smoking Prevention Project ( HSPP ) , conducted from September 1984 through August 1999 , aim ed to attain the most rigorous r and omized trial possible to determine the long-term impact of a theory-based , social-influences , grade 3 - 12 intervention on smoking prevalence among youth . METHODS Forty Washington school districts were r and omly assigned to the intervention or to the control condition . Study participants were children enrolled in two consecutive 3rd grade s in the 40 districts ( n = 8388 ) ; they were followed to 2 years after high school . The trial achieved high implementation fidelity and 94 % follow-up . Data were analyzed with the use of group-permutation methods , and all statistical tests were two-sided . RESULTS No significant difference in prevalence of daily smoking was found between students in the control and experimental districts , either at grade 12 ( difference [ Delta ] = 0.2 % , 95 % confidence interval [ CI ] = -4.6 % to 4.4 % , and P = .91 for girls ; Delta = 0.3 % , 95 % CI = -5.0 % to 5.5 % , and P = .89 for boys ) or at 2 years after high school ( Delta = -1.4 % , 95 % CI = -5.0 % to 1.6 % , and P = .38 for girls ; Delta = 2.6 % , 95 % CI = -2.5 % to 7.7 % , and P = .30 for boys ) . Moreover , no intervention impact was observed for other smoking outcomes , such as extent of current smoking or cumulative amount smoked , or in subgroups that differ in a priori specified variables , such as family risk for smoking . CONCLUSION The rigor of the HSPP trial suggests high credence for the intervention impact results . Consistent with previous trials , there is no evidence from this trial that a school-based social-influences approach is effective in the long-term deterrence of smoking among youth This study examined the effects of the Iowa Strengthening Families Program ( ISFP ) and the Preparing for the Drug-Free Years program ( PDFY ) on young adolescent transitions from nonuse of substances to initiation and progression of substance use . Analyses incorporated 3 waves of data collected over a 2.5-year period from 329 rural young adolescents . Outcomes were analyzed by using log-linear models that incorporated substance use status frequencies derived from latent transition analyses . Effects on delayed substance use initiation were shown for both the ISFP and the PDFY at a 2-year follow-up . Also at this follow-up , the PDFY showed effects on delayed progression of use among those previously reporting initiation Recent studies have suggested that a prevention program that addresses the social influences that encourage smoking can be effective in deterring cigarette use by adolescents . This study presents 1- , 2- , and 3-year follow-up results from two studies which evaluated three variations of the social influences curriculum and compared them to a health consequences program and a usual-care comparison group . These results suggest that a peer-led , social influences program can restrain smoking among both baseline nonsmokers and baseline experimental smokers at 2 years postintervention . Analyses of attrition data suggest no evidence to threaten the internal validity of these findings , although their generalizability to baseline smokers may be limited This study reports the evaluation of an intervention design edto reinforcetobacco abstinence amongelementary schoolchildren in a school transition period . This intervention was developed according to the principles of Intervention Mapping . A total of 765 grade 5 students ( ages 10 - 12 ) was recruited in 32 elementary schools . A quasi-experimental longitudinal design was used to evaluate the outcomes . Results observed 2 and 8 months postintervention are reported here . It is shown that although the behavior remained largely unchanged by the intervention , some of its determinants were modified . Behavioral intention , behavioral and normative beliefs , perceived self-efficacy , and role beliefs were changed at one or both postintervention measures . An interesting feature of these results relates to the fact that the most positive outcomes were seen among at-risk children . Discussion considers the advisability to develop , implement , and evaluate evidence -based interventions targeting the psychosocial factors underlying maintenance of tobacco smoking abstinence in elementary school Most school-based smoking prevention studies employ design s in which schools or classrooms are assigned to different treatment conditions while observations are made on individual students . This design requires that the treatment effect be assessed against the between-school variance . However , the between-school variance is usually larger than the variance that would be obtained if students were individually r and omized to different conditions . Consequently , the power of the test for a treatment effect is reduced , and it becomes difficult to detect important treatment effects . To assess the potential loss of power or to calculate appropriate sample sizes , investigators need good estimates of the intraclass correlations for the variables of interest . The authors calculated intraclass correlations for some common outcome variables in a school-based smoking prevention study , using a three-level model-i.e . , students nested within classrooms and classrooms nested within schools . The authors present the intraclass correlation estimates for the entire data set , as well as separately by sex and ethnicity . They also illustrate the use of these estimates in the planning of future studies Outcome research has shown that drug prevention programs based on theories of social influence often prevent the onset of adolescent drug use . However , little is known empirically about the processes through which they have their effects . The purpose of the present study was to evaluate intervening mechanism theories of two program models for preventing the onset of adolescent drug use . Analyses based on a total of 3077 fifth grade rs participating in the Adolescent Alcohol Prevention Trial revealed that both normative education and resistance training activated the causal processes they targeted . While beliefs about prevalence and acceptability significantly mediated the effects of normative education on subsequent adolescent drug use , resistance skills did not significantly predict subsequent drug use . More impressively , this pattern of results was virtually the same across sex , ethnicity , context ( public versus private school students ) , drugs ( alcohol , cigarettes , and marijuana ) and levels of risk and was durable across time . These findings strongly suggest that successful social influence-based prevention programs may be driven primarily by their ability to foster social norms that reduce an adolescent 's social motivation to begin using alcohol , cigarettes , and marijuana BACKGROUND Physicians ' advice to help pregnant women quit smoking during prenatal care has had mixed results . Training and prompting physicians to provide consistent advice and referral to on-site support might improve cessation rates . METHODS Pregnant women who smoked were r and omly assigned to receive structured advice from their physician and referral to individual behavior change counseling during prenatal care or to receive brief advice to stop smoking and a quit smoking booklet at their first visit . Smoking status was measured by self-report , exhaled carbon monoxide , and urinary cotinine . RESULTS Compared with usual care , greater proportions of intervention group women reported not smoking at the 36th-week visit ( 14 % vs 10 % ) and at 1 year postpartum ( 18 % vs 11 % ) , but these differences were not significant . However , significantly greater proportions of intervention group women reported either not smoking or reducing their cigarette consumption by 50 % or more at their second visit ( 43 % vs 29 % , P = 0.02 ) , at their 36th-week visit ( 40 % vs 25 % , P < 0.01 ) , and at 1 year postpartum ( 26 % vs 14 % , P = 0.02 ) . CONCLUSIONS Physician training on how to gain a pregnant smoker 's commitment to change her smoking behavior , an office prompt system , and individualized smoking behavior change counseling show promise in reducing smoking during pregnancy and postpartum , but practical methods to assist pregnant smokers between regular prenatal visits , as they attempt to quit , need to be developed This article review s major risk factors for cigarette smoking , alcohol , and other drug abuse and promising community-based approaches to primary prevention . In a longitudinal experimental study , 8 representative Kansas City communities were assigned r and omly to program ( school , parent , mass media , and community organization ) and control ( mass media and community organization only ) conditions . Programs were delivered at either 6th or 7th grade , and panels were followed through Grade 9 or 10 . The primary findings were ( a ) significant reductions at 3 years in tobacco and marijuana use and ( b ) equivalent reductions for youth at different levels of risk . This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk OBJECTIVES Our study tested the effectiveness of network methods for identifying opinion leaders and for constructing groups . METHODS Three conditions-r and om , teacher , and network -- ere r and omly assigned to 84 6th- grade classrooms within 16 schools . Pre- and postcurriculum data on mediators of tobacco use were collected from 1961 students . Peer leaders in the network condition were identified by student nominations , and those leaders were matched with the students who nominated them . RESULTS Students in the network condition relative to the r and om condition liked the prevention program more and had improved attitudes ( beta = -0.06 ; P < .01 ) , improved self-efficacy ( beta = -0.10 ; P < .001 ) , and decreased intention to smoke ( adjusted odds ratio [ OR ] = 0.46 ; 95 % confidence interval [ CI ] = 0.38 , 0.55 ) . CONCLUSIONS The network method was the most effective way to structure the program . Future programs may refine this technique and use it in other setting This study examined the effects of a smoking prevention program on the acquisition of refusal skills among junior high school students . Two conditions were compared : one in which the subjects participated in a videotaped training program on resisting pressures to smoke , and the other an untreated control group . As predicted , the results showed significant improvement in the skill training group , while the untreated controls showed no change relative to their pretest performance . These findings suggest that smoking prevention programs which focus on resisting social pressures can enhance the young person 's ability to say " no " to smoking BACKGROUND Interventions design ed to prevent tobacco and alcohol use targeting high-risk adolescents are limited . In addition , few studies have attempted to improve parent-child communication skills as a way of improving and maintaining healthy youth decision-making . METHODS A total of 660 Hispanic migrant families participated in a r and omized pre-post control group study that was utilized to determine the impact of the intervention on parent-child communication . Both treatment and attention-control groups of youth were exposed to an eight-session culturally sensitive program presented by bilingual/bicultural college students . Parents jointly attended three of the eight sessions and participated in helping their child complete homework assignments supporting the content of each session . The content of the treatment intervention included ( 1 ) information about tobacco and alcohol effects , ( 2 ) social skills training ( i.e. , refusal skills ) , and ( 3 ) the specific development of parent-child communication skills to support healthy youth decisions . RESULTS Significant intervention by household size interactions for both parent and youth perceptions of communication were found indicating that the treatment was effective in increasing communication in families with fewer children . Based on the effect size and the previously established relationship between communication and susceptibility to tobacco and alcohol use , it was determined that the intervention effect could be translated into a future 5 to 10 % decrease in susceptibility for these smaller families . CONCLUSIONS A culturally sensitive family-based intervention for migrant Hispanic youth was found to be effective in increasing perceived parent-child communication in families with fewer children . It is expected that increases in this important protective factor will lead to later observed decreases in tobacco and alcohol use The present study was design ed to test the feasibility , acceptability , and effectiveness of a 15-session smoking prevention intervention with a predominantly hispanic ( 74 % ) sample of seventh- grade students ( N=471 ) in eight urban schools in the New York area . The smoking prevention curriculum teaches social resistance skills within the context of a broader intervention promoting general personal and social competence and was implemented in this study by regular classroom teachers . Results of logistic regression analyses provided preliminary evidence of the efficacy of this type of smoking prevention strategy with urban minority youth when implemented with a reasonable degree of fidelity . The significance of these findings is that they provide support for the generalizability of an approach previously found to be effective with white middle-class population s to a predominantly hispanic inner-city population Background Smoking rates are projected to increase substantially in developing countries such as South Africa . Purpose The aim of this study was to test the efficacy of two contrasting approaches to school-based smoking prevention in South African youth compared to the st and ard health education program . One experimental program was based on a skills training/peer resistance model and the other on a harm minimization model . Method Thirty-six public schools from two South African provinces , KwaZulu-Natal and the Western Cape , were stratified by socioeconomic status and r and omized to one of three groups . Group 1 ( comparison ) schools ( n = 12 ) received usual tobacco use education . Group 2 schools ( n = 12 ) received a harm minimization curriculum in grade s 8 and 9 . Group 3 schools ( n = 12 ) received a life skills training curriculum in grade s 8 and 9 . The primary outcome was past month use of cigarettes based on a self-reported question naire . Result Five thous and two hundred sixty-six students completed the baseline survey . Of these , 4,684 ( 89 % ) completed at least one follow-up assessment . The net change in 30-day smoking from baseline to 2-year follow-up in the control group was 6 % compared to 3 % in both harm minimization ( HM ) and life skills training ( LST ) schools . These differences were not statistically significant . Intervention response was significantly moderated by both gender and race . The HM intervention was more effective for males , whereas the life skills intervention was more effective for females . For black African students , the strongest effect was evident for the HM intervention , whereas the strongest intervention effect for “ colored ” students was evident for the LST group . Conclusion The two experimental curricula both produced similar overall reductions in smoking prevalence that were not significantly different from each other or the control group . However , the impact differed by gender and race , suggesting a need to tailor tobacco and drug use prevention programs . More intensive intervention , in the classroom and beyond , may be needed to further impact smoking behavior Background : Prevention of youth smoking has great potential to improve the health of Americans . There is limited information about correlates of tobacco use among adolescents from ethnic minority groups , especially Asians , Pacific Isl and ers , and Native Hawaiians . Purpose : This article examines the relationships among ethnicity , sense of coherence ( SOC ) , and tobacco use . Methods : We conducted a baseline survey of a cluster r and omized tobacco prevention trial in public middle schools in Hawaii with a multiethnic sample of 3,438 seventh- grade students . Results : Ethnic differences in smoking prevalence were very large , with high smoking rates among Native Hawaiian/Pacific Isl and er , White , and Filipino students and with low rates among Japanese and Chinese students . Higher SOC scores predicted significantly lower risk of having ever smoked and of smoking in the past 30 days , SOC was most strongly related to ever smoking among Filipino , Hawaiian/Pacific Isl and er , and While students ; Japanese students experienced the strongest protective effect from SOC for past-month smoking . Conclusions : The results suggest that SOC is strongly associated with tobacco use among this age group . It will be important to examine whether SOC can be improved by an intervention program and whether increases in SOC are associated with reduced smoking The purpose of this study was to compare longitudinal smoking prevention program effects estimated on a population -based cohort sample of sixth- and seventh- grade students ( average n per year = 4,664 ) using different schools as units of analysis ( middle/junior high school as the school of origin or high school as the endpoint school of intervention ) . Fifty schools in 15 school districts were demographically matched and assigned to either a school and community-based program for prevention of cigarette , alcohol , and marijuana use , or a health education as usual control group . Smoking was measured by question naires administered to the students . An expired air ( CO ) measure of smoking was also administered to increase accuracy of self-reports . Program effects were estimated with regression analyses , controlling for school-level socioeconomic status , racial/ethnic make-up , urbanicity , and grade . Using school of origin as the unit of analysis , program effects showed 1 year net reductions of -8 , -6 , and -5 % in prevalence rates of smoking in the last month , last week , and last 24 hr ; 2-year program effects showed similar net reductions of -6 , -5 , and -3 % ( P 's less than 0.10 - 0.001 ) . Analyses with endpoint school as the unit showed slightly weaker effects at the 2-year follow-up , the year during which 64 % of students had moved to a junior high or high school . The findings are discussed in terms of the potential contamination of experimental groups in longitudinal studies from school consolidations , family mobility , and feeder patterns to high schools , and the different smoking environments represented by middle , junior high , and high schools A major issue in smoking prevention research is that no study has tried to equate program success expectancies across experimental and placebo control conditions . Equivalent overall program success expectancies should be established to help rule out the effects of extra-theoretical variables which influence program outcomes . The present study tested whether an attention-placebo ( information based ) smoking prevention program would produce equivalent expectancies about the likelihood of program success in comparison to an experimental social influences program . To try to equate program success expectancies , the design of the two programs differed in content but was similar in procedure . Fourteen middle schools were r and omly assigned to the two conditions . As hypothesized , baseline expectancies were found to predict outcome measures , even after controlling for baseline smoking intentions , ethnic group , and gender . Second , the equivalence of program expectancies at posttest was tested . Youths held equivalent overall expectancies for success across conditions . This study suggested the need to control for program expectancies in prevention research , and showed that program expectancies could be controlled for by equating process of program delivery A grade five through eight substance abuse prevention program , later incorporated into the Michigan Model for Comprehensive School Health Education , was developed , implemented , and evaluated . Results focus on students who received seven lessons on alcohol in grade six , and eight lessons on tobacco , alcohol , marijuana , and cocaine in grade seven taught by their regular classroom teachers ( after a 6-hour training in the social pressures resistance skills curriculum ) . Students ( N = 442 ) received either two years of the program or none , and completed individually-coded question naires . Repeated measures analysis of variance result ed in significant treatment by occasion interactions on the use of alcohol , cigarettes , marijuana , cocaine , and other drugs , as well as on knowledge . At the end of grade seven , program students ' rates of substance use had increased significantly less and knowledge of alcohol pressures , effects , and skills to resist had increased significantly more than those of comparison students BACKGROUND Smoking prevention programs usually run during school hours . In our study , an out-of-school program was developed consisting of a computer-tailored intervention aim ed at the age group before school transition ( 11- to 12-year-old elementary schoolchildren ) . The aim of this study is to evaluate the additional effect of out-of-school smoking prevention . METHODS One hundred fifty-six participating schools were r and omly allocated to one of four research conditions : ( a ) the in-school condition , an existing seven-lesson program ; ( b ) the out-of-school condition , three computer-tailored letters sent to the students ' homes ; ( c ) the in-school and out-of-school condition , a combined approach ; ( d ) the control condition . Pretest and 6 months follow-up data on smoking initiation and continuation , and data on psychosocial variables were collected from 3,349 students . RESULTS Control and out-of-school conditions differed regarding posttest smoking initiation ( 18.1 and 10.4 % ) and regarding posttest smoking continuation ( 23.5 and 13.1 % ) . Multilevel logistic regression analyses showed positive effects regarding the out-of-school program . Significant effects were not found regarding the in-school program , nor did the combined approach show stronger effects than the single- method approaches . CONCLUSIONS The findings of this study suggest that smoking prevention trials for elementary schoolchildren can be effective when using out-of-school computer-tailored interventions Psychosocial tobacco use prevention programs are based on the assumption that refusal skills training will have a suppressive effect on the onset of use by enabling non-using adolescents to refuse offers of cigarettes and smokeless tobacco . The present study investigated this assumption with 389 high-risk junior high-school students involved in a prevention program during their seventh , eighth , and ninth- grade years . Direct behavioral measures of refusal skills were taken by having subjects respond to audiotaped offers of tobacco and then rating the quality of their responses . These ratings were then linked to tobacco use measures obtained at the end of each of the 3 study years . Results showed that the comprehensive prevention program produced a favorable trend in delaying or preventing the onset of tobacco use . However , the refusal skills training , which was carried out throughout the 3-year intervention period , produced significant differences in overall refusal skill quality only at the seventh grade . Moreover , refusal skill quality was not related to overall tobacco use or cigarette use at any grade As part of a larger study to evaluate the impact of a state-levied tax increase on tobacco products and the allocation of funds for smoking education , 81 schools were assigned r and omly to one of four recommended smoking prevention programs for adolescents . The four programs differed in amount of program structure and extent of teacher training required . A one-session observation was made of 106 teachers in the 81 schools to assess the percentage of time allocated to recommended activities -- those based on the social influences model . Data suggest an explicit curriculum with design ed activities and face-to-face teacher training results in greater compliance to prescribed program components This study developed and tested a gender-specific intervention for preventing substance abuse among adolescent girls . Delivered on CD-ROM by computer , the program was compared with a conventional substance abuse prevention program delivered live in a group setting . Seventh- grade girls in New York City middle schools completed pretests , and , by school , were r and omly assigned to receive either gender-specific computer intervention ( GSI ) or conventional intervention , and were posttested . Analyses of pretest to posttest gain scores showed GSI girls compared to girls receiving conventional intervention to possess a larger repertoire of stress-reduction methods , to report lower approval of cigarettes , alcohol , and drugs , to identify more unhealthy ways to deal with stress , to report lower likelihood of cigarette use or alcohol consumption if asked to do so by best friends , and to hold stronger plans to avoid cigarettes , alcohol , and drugs in the next year . These modest findings lend credence to the promise of gender-specific , computerized interventions for substance use prevention among adolescent girls The research community has criticized Drug Abuse Resistance Education ( D.A.R.E. ) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use . Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support . To date , the junior high D.A.R.E. program has not been evaluated . The Minnesota DARE PLUS Project is a r and omized trial of 24 schools and communities . During 1999 - 2001 , students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade ; eight schools also will receive the curriculum as well as additional parent involvement , peer leadership , and community components in the 7th and 8th grade s ; and eight schools will serve as controls . This article describes the background and conceptualization , the curriculum and additional intervention components , and the evaluation methods of the DARE PLUS Project OBJECTIVES This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse ( Project TND ) , a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth , who are at high risk for drug abuse . METHODS The efficacy of nine-lesson health motivation -- social skills -- decision-making curriculum was evaluated in a three-condition experimental design . Twenty-one schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , classroom program , and classroom program plus a semester-long school-as-community component . A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools . The 7 st and ard care schools received only the pretest followed by the posttest ( same time duration ) . Subjects were followed up 1 year later . RESULTS Changes in use of cigarettes , alcohol , marijuana , and hard drugs were assessed in a pretest-1-year follow-up time interval . The follow-up rate was 67 % ( analysis n = 1,074 ) . Indicated preventive effects were found on alcohol and hard drug use . No differences were found across the two program conditions . CONCLUSIONS Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older , high-risk youth by using a school-based , limited-session model OBJECTIVES The purpose of this study was to implement and evaluate the effectiveness of a long-term tobacco use prevention program for junior high school students that used college undergraduate change agents and telephone boosters . METHODS A psychosocial intervention combining refusal skills training , contingency management , and other tobacco use prevention method ologies such as telephone and mail boosters was implemented in 11 junior high schools in San Diego County , California . Eleven other junior high schools served as controls . Of the 2668 participants , 57 % were White/non-Hispanic , 24 % were Hispanic , and 19 % were of other racial/ethnic groups . College undergraduates served as change agents for both the classroom and booster interventions , the latter of which was delivered in the third ( ninth- grade ) year of the program . RESULTS At the end of the third year , the prevalence of tobacco use within the past month was 14.2 % among the intervention students and 22.5 % among the controls , yielding an odds ratio of 0.71 for analysis at the school level . CONCLUSIONS Both college undergraduate change agents and direct one-to-one telephone interventions appear to provide cost-effective tobacco-related behavior modification OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention This study was design ed to create , implement , and test a school-based multiple risk factor reduction program for high school students . All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in the study . Within each district , one school was assigned at r and om to receive a special 20-session CVD risk reduction intervention and one school served as a control . The schools were matched for size and distribution of racial groups before r and omization . At a two-month follow-up , knowledge gains were significantly greater for students in the treatment group on each of the risk factor domains tested : nutrition/diet ( p less than 0.0001 ) , physical activity ( p less than 0.0001 ) , and cigarette smoking ( p less than 0.0001 ) . Compared to controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline , reported regular exercise at follow-up ( p less than 0.0003 ) . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared to 10.3 % in the control group ( p = 0.009 ) . Students in the treatment group were more likely to report that they would choose heart healthy snack items ( p less than 0.0001 ) . Beneficial treatment effects were observed for resting heart rate ( p less than 0.0001 ) , BMI ( p = 0.05 ) , triceps skinfold thickness ( p = 0.003 ) , and subscapular skinfold thickness ( p = 0.01 ) . The results suggest that it is feasible to provide CVD risk reduction training to a large segment of the population through school-based primary prevention approaches Sirice 1974 an anti-smoking campaign consisting of a one-day educational intervention has been carried out in primary schools in Milan by the Italian League against Cancer ( Milan Division ) . All but two of the 165 schools were r and omized to evaluate the intervention effect . A total of 8549 children aged 9 - 10 were allocated to the intervention group and 8897 to the control group . Four years later a self-administered question naire was distributed in order to investigate the children 's smoking habits . The proportion of smokers was 8.05 % and 8.72 % ( p = 0.23 ) respectively for the intervention and control groups . It was concluded that sporadic educational Intervention carried out during primary school years has little or no impact in preventing cigarette smoking in teenagers OBJECTIVES This study investigated the efficacy of a social-influences tobacco prevention program conducted with adolescents living in a high tobacco production area . METHODS Students in 10 experimental schools completed the tobacco prevention program and a booster intervention . Control students received health education as usual . RESULTS After 2 years of treatment , smoking rates in the treatment group ( vs the control group ) were lower for 30-day , 7-day , and 24-hour smoking . The intervention had more of an impact on those who were involved in raising tobacco than it did on those not involved in raising tobacco . CONCLUSIONS Although modest , effects were achieved with minimal intervention time in a high-risk group , indicating that social-influences prevention programs may be effective in such groups Tobacco and drug use remain major public health concerns . The aim of this study was to evaluate the effectiveness of a school health intervention program using life skills training ( LST ) to reduce tobacco and drug use among Thai high school students . A r and omized pretest and post-test comparative design was used to evaluate the effectiveness of the LST program . A total of 170 Thai students in grade s 7 - 12 were r and omly selected . The students in the control group received the tobacco and drug education curriculum normally provided ; the intervention group received a LST program that provided information and skills specifically related to drug and tobacco use . Students in the school health intervention program had statistically significant positive effects regarding knowledge level , attitudes , and the development of refusal , decision-making , and problem-solving skills . The results showed that a LST program was effective for preventing tobacco and drug use in Thai high school students BACKGROUND This paper presents the student outcomes of a large-scale , social-influences-based , school and media-based tobacco use prevention and cessation project in Southern California . METHODS The study provided an experimental comparison of classroom delivery with television delivery and the combination of the two in a 2 x 2 plus 1 design . Schools were r and omly assigned to conditions . Control groups included " treatment as usual " and an " attention control " with the same outcome expectancies as the treatment conditions . Students were surveyed twice in grade 7 and once in each of grade s 8 and 9 . The interventions occurred during grade 7 . RESULTS We observed significant effects on mediating variables such as knowledge and prevalence estimates , and coping effort . The knowledge and prevalence estimates effects decayed partially but remained significant up to a 2-year follow-up . The coping effort effect did not persist at follow-ups . There were significant main effects of both classroom training and TV programming on knowledge and prevalence estimates and significant interactions of classroom and TV programming on knowledge ( negative ) , disapproval of parental smoking , and coping effort . There were no consistent program effects on refusal/self-efficacy , smoking intentions , or behavior . CONCLUSIONS Previous reports demonstrated successful development and pilot testing of program components and measures and high acceptance of the program by students and parents . The lack of behavioral effects may have been the result of imperfect program implementation or low base rates of intentions and behavior OBJECTIVE To provide a review of the evidence from 3 experimental trials of Project Towards No Drug Abuse ( TND ) , a senior-high-school-based drug abuse prevention program . METHODS Theoretical concepts , subjects , design s , hypotheses , findings , and conclusions of these trials are presented . A total of 2,468 high school youth from 42 schools in southern California were surveyed . RESULTS The Project TND curriculum shows reductions in the use of cigarettes , alcohol , marijuana , hard drugs , weapon carrying , and victimization . Most of these results were replicated across the 3 trials . CONCLUSION Project TND is an effective drug and violence prevention program for older teens , at least for one-year follow-up This study evaluated cigarette smoking prevention methods with a sample of adolescent females and males . Arranged by school , 331 informed and consenting sixth grade rs were r and omly divided into four groups : 1 ) pretest , skills-building methods , posttest ; 2 ) pretest , discussion methods , posttest ; 3 ) pretest and posttest ; and 4 ) posttest only . All subjects were followed for 6 and 15 months after the posttest . Outcome results on measures of non-smoking intentions , attitudes , predictions , problem-solving abilities , and peer interactions favored subjects in the skills-building group when compared with subjects in the discussion and pretest-posttest control groups . Smoking rates at posttest and at both follow-ups were lower in the skills-building group than in the other three groups . Results from posttest-only subjects did not support pretest reactivity . The study 's strengths and limits are discussed along with directions for future smoking prevention research An amenability to treatment model stipulates that interventions may be differentially effective for subgroups of individuals with similar characteristics . Using such a model , the present study tests the impact of two social-cognitive interventions implemented in the sixth ( Intervention I ) and eighth/ninth ( Intervention II ) grade s on students ' skill acquisition and on their ninth and tenth grade substance use . A r and omized factorial design was used to examine main and interaction effects within the context of student family household status and gender . Positive program effects were found for Intervention II on skill acquisition and overall drug involvement . Interaction effects of Intervention II x Family Household Status provided support for the amenability to treatment model , but no support for the model was observed based on student gender . Possible explanations for the study findings are presented and future research directions are proposed to address why differences emerge in amenability to intervention and why such differences occur for specific subgroups BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention Nonadherence to accepted design principles for r and omized trials has been a limitation of school-based intervention research . Design ed to overcome these limitations , the Hutchinson Smoking Prevention Project ( HSPP ) is a 15-year r and omized trial to determine the extent to which a school-based ( grade s 3 - 12 ) tobacco use prevention intervention can deter youth tobacco use throughout and beyond high school . This paper presents the HSPP experimental design , together with methods for its implementation , and an evaluation of the degree to which HSPP has adhered to principles of r and omized trials . Results from the experimental design and its conduct include ( 1 ) a recruitment rate of 97.6 % ( 40 of 41 targeted school districts ) , ( 2 ) full and active participation for the trial 's duration by 100 % of the 40 school districts recruited , ( 3 ) implementation by virtually all teachers ( 99%+ ) , with 86 % implementation fidelity , and ( 4 ) outcome determination for 94.3 % ( 7910 ) of 8388 original study participants identified 12 years previously at baseline . The high degree of rigor achieved by the HSPP experimental design ensures confidence in the trial 's soon-to-be available intervention effectiveness results . Equally important , for future school-based trials , the HSPP design and its execution have illustrated that school-based research can adhere to the principles of rigorous r and omized trials , with high rates of implementation , and very high rates of recruitment , maintenance , and follow-up of study participants , even for studies with decade-long follow-up periods . Rigor in school-based trials can be achieved through a combination of ( 1 ) commitment to the principles of r and omized trials , ( 2 ) attention to the special challenges of trials specific to the school setting , ( 3 ) adoption and meticulous execution of proven methods for trial conduct , and ( 4 ) establishment at the outset of principles for maintaining positive collaborative relationships with participating school districts for the duration of the trial . These findings are important in light of the great potential for using the nation 's schools to access youth for health promotion/risk-factor prevention This study reports findings on a combined family and school-based competency-training intervention from an in-school assessment 2.5 years past baseline , as a follow-up to an earlier study of substance initiation . Increased rates of observed alcohol use and an additional wave of data allowed evaluation of regular alcohol use and weekly drunkenness , with both point-in-time and growth curve analyses . Thirty-six rural schools were r and omly assigned to ( a ) a combined family and school intervention condition , ( b ) a school-only condition , or ( c ) a control condition . The earlier significant outcome on a substance initiation index was replicated , and positive point-in-time results for weekly drunkenness were observed , but there were no statistically significant outcomes for regular alcohol use . Discussion focuses on factors relevant to the mix of significant longitudinal results within a consistent general pattern of positive intervention-control differences This paper evaluates a smoking prevention intervention aim ed at vocational school students , consisting of an existing Dutch in-school program ( three lessons each lasting 50 min ) and a computer-based tailored out-of-school program ( three tailored letters with smoking prevention messages mailed to students ' homes ) . Nineteen schools that already participated in the in-school program were r and omly assigned to the in-school or to the combined in-school and out-of-school condition . The remaining 17 schools were r and omly assigned to the out-of-school condition or to the control group . Effect outcomes were assessed at 6 , 12 and 18 months after a pre-test , and were based on initiation among never-smokers and continuation among ever-smokers . Twelve months after the pre-test ( post-test 2 ) , the in-school intervention was successful in preventing vocational school students from continuing to smoke , compared with students in the control condition [ odds ratio ( OR ) = 0.49 ; 95 % confidence interval ( CI ) = 0.29 - 0.84 ] . Eighteen months after the pre-test ( post-test 3 ) , the tailored out-of-school intervention was successful in preventing smoking initiation , compared with students in the control condition ( OR = 0.42 ; 95 % CI = 0.18 - 0.96 ) . The effect of the combined approach was not larger than the sum of the effects of the in-school and the out-of-school effects This study used Complier Average Causal Effect analysis ( CACE ; see G. Imbens & D. Rubin , 1997 ) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11 - 17 . Students were r and omly assigned to a family-centered intervention ( N = 998 ) in 6th grade and offered a multilevel intervention that included ( a ) a universal classroom-based intervention , ( b ) the Family Check-Up ( selected ; T. J. Dishion & K. Kavanagh , 2003 ) , and ( c ) family management treatment ( indicated ) . All services were voluntary , and approximately 25 % of the families engaged in the selected and indicated levels . Participation in the Family Check-Up was predicted by 6th- grade teacher ratings of risk , youth reports of family conflict , and the absence of biological fathers from the youths ' primary home . Relative to r and omized matched controls , adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol , tobacco , and marijuana use and problem behavior during ages 11 through 17 , along with decreased risk for substance use diagnoses and police records of arrests by age 18 BACKGROUND Universal school-based prevention programs for alcohol , tobacco , and other drug use are typically design ed for all students within a particular school setting . However , it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation . METHOD The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a r and omized , controlled prevention trial . A sub sample of youth ( 21 % of full sample ) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school . The prevention program taught drug refusal skills , antidrug norms , personal self-management skills , and general social skills . RESULTS Findings indicated that youth at high risk who received the program ( n = 426 ) reported less smoking , drinking , inhalant use , and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention ( n = 332 ) . Results indicate that a universal drug abuse prevention program is effective for minority , economically disadvantaged , inner-city youth who are at higher than average risk for substance use initiation . CONCLUSIONS Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk BACKGROUND The Good Behavior Game ( GBG ) , a method of classroom behavior management used by teachers , was tested in first- and second- grade classrooms in 19 Baltimore City Public Schools beginning in the 1985 - 1986 school year . The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive , disruptive behaviors , confirmed antecedents of later substance abuse and dependence disorders , smoking , and antisocial personality disorder . This article reports on impact to ages 19 - 21 . METHODS In five poor to lower-middle class , mainly African American urban areas , three or four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a curriculum- and -instruction program directed at reading achievement , or ( 3 ) the st and ard program . Balanced assignment of children to classrooms was made , and then , within intervention schools , classrooms and teachers were r and omly assigned to intervention or control . RESULTS By young adulthood significant impact was found among males , particularly those in first grade who were more aggressive , disruptive , in reduced drug and alcohol abuse/dependence disorders , regular smoking , and antisocial personality disorder . These results underline the value of a first- grade universal prevention intervention . REPLICATION : A replication was implemented with the next cohort of first- grade children with the same teachers during the following school year , but with diminished mentoring and monitoring of teachers . The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation . For other outcomes the effects were generally smaller but in the predicted direction This study investigated both substantive and method ological issues associated with school-based smoking prevention programs . Substantive issues included the efficacy of a refusal skills training curriculum and of parent messages mailed to students ' homes . Method ological issues included the effects of assigning classrooms versus entire schools to experimental conditions and determination of the effects of attrition on internal and external validity . Results revealed differential impact for different subgroups of adolescents . The refusal skills program produced lower rates of smoking than the control condition for students who were smokers at the pretreatment assessment but may have produced detrimental effects among males who were nonsmokers at pretest . The provision of parent messages did not affect outcome . Method of assignment ( schools versus classrooms ) failed to produce significant effects , and attrition did not affect internal validity . However , the above differential findings , as well as the impact of attrition on external validity , raise questions concerning the generalizability of smoking prevention programs Raising Healthy Children ( RHC ) is a preventive intervention design ed to promote positive youth development by targeting developmentally appropriate risk and protective factors . In this study , the authors tested the efficacy of the RHC intervention on reducing adolescent alcohol , marijuana , and cigarette use . Ten public schools , which comprised 959 1st- and 2nd- grade students ( 54 % male students , 18 % minority , 28 % low socioeconomic status ) , were matched and assigned r and omly to either intervention or control conditions . A 2-part latent growth modeling strategy was used to examine change in both use-versus-nonuse and frequency-of-use outcomes while students were in Grade s 6 - 10 . Results indicated significant ( p < .05 ) intervention effects in growth trajectories for frequency of alcohol and marijuana use but not for use versus nonuse . These findings provide support for preventive interventions that take a social development perspective in targeting empirically supported risk and protective factors and demonstrate the use of 2-part models in adolescent substance use research This study tested the hypothesis that cigarette smoking adoption among adolescents could be suppressed by providing school-based videotape instruction for resisting social influences to smoke . The utilization of same-age peer leaders was also varied to test whether their participation in the classroom would enhance program effects . Seventh grade students ( N = 540 ) from one junior high school in Southern California were r and omly assigned by classrooms ( N = 15 ) to : ( a ) videotape instruction , ( b ) videotape instruction plus peer leader involvement , or ( c ) survey-only . Seventh grade students ( N = 234 ) in a second junior high school served as a measurement-only control . Assessment s were conducted at the beginning and end of the academic year . Results revealed a marked suppression in the onset of both experimental and regular smoking among those students exposed to the pressure resistance training with peer leader involvement . Pressure resistance training without peer leader involvement produced a more variable and less powerful effect on students ' smoking behavior . Data collected on students ' use of alcohol and marijuana revealed a generalized suppression effect , albeit weaker than for tobacco , among those students exposed to the social resistance training with peer leader involvement . Results provide further encouraging support for the use of peer-led pressure resistance training in preventing adolescent drug use BACKGROUND The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures . The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies . METHODS The Four Group Comparison Study was a prospect i ve study of 48 school " units " which were r and omly assigned to one of four conditions in 1987 . Baseline observations were taken in the sixth grade in 1987 , interventions were delivered in the seventh grade , and follow-up observations were taken in the seventh , eighth , and ninth grade s. The Four Group Comparison Study was design ed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation . The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin . Annual surveys of ninth grade rs were conducted from 1986 - 1990 . The Two State Comparison Study was design ed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation . RESULTS The prospect i ve study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a r and omized control group . The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990 , but that it was within the range of chance variation . CONCLUSIONS Taken together , these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period . Together with results from other recent studies , they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research While most intervention studies on coronary heart disease have focused on the high-risk person only , the present study used the family as the unit of intervention . In the study 1373 high-risk men , ages 30 - 54 years , were identified on the basis of high total cholesterol ( TC ) and /or low relative high-density lipoprotein cholesterol ( HDL-C ) ( HDL-C/TC ) following the 1979/1980 survey in Tromsø . The men and their families were r and omly allocated to a control or intervention condition . The intervention families were given advice on diet , smoking , and exercise . At rescreening in 1986/1987 , significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group . For children , the differences were small and mostly nonsignificant . Men , spouses , and children in the intervention group reported more favorable dietary habits than those in the control group . No differences were found in smoking or leisure time physical activity AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking In this article , we examine the impact of two universal , grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence . The classroom-centered ( CC ) intervention was design ed to reduce the risk for tobacco smoking by enhancing teachers ' behavior management skills in first grade and , thereby , reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use . The family-school partnership ( FSP ) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents ' child behavior management strategies . A cohort of 678 urban , predominately African-American , public school students were r and omly assigned to one of three Grade 1 classrooms at entrance to primary school ( age 6 ) . One classroom featured the CC intervention , a second the FSP intervention , and the third served as a control classroom . Six years later , 81 % of the students completed audio computer-assisted self-interviews . Relative to controls , a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms ( 26 % versus 33 % ) ( adjusted relative risk for CC/control contrast=0.57 , 95 % confidence interval ( CI ) , 0.34 - 0.96 ; adjusted relative risk for FSP/control contrast=0.69 , 95 % CI , 0.50 - 0.97 ) . Results lend support to targeting the early antecedent risk behaviors for tobacco smoking BACKGROUND The study 's objective was to examine the effects of " real-world , " community-based implementation of universal preventive interventions selected from a menu , including effects specific to higher- and lower-risk sub sample s. DESIGN School districts were selected based on size and location , and then r and omly assigned to a control condition or to an experimental condition in a cohort sequential design . SETTING / PARTICIPANTS The study included 28 public school districts in Iowa and Pennsylvania that were located in rural towns and small cities , ranging in size from 6975 to 44,510 . Sixth and seventh grade rs in these school districts participated in the study . INTERVENTION Community teams were mobilized ; each team implemented one of three evidence -based , family-focused interventions ( 5 to 12 sessions ) and one of three evidence -based school interventions ( 11 to 15 sessions ) , for 6th and 7th grade rs , respectively . Observations showed that interventions were implemented with fidelity . MAIN OUTCOME MEASURES Outcomes included student reports of past month , past year , and lifetime use of alcohol , cigarettes , marijuana , methamphetamines , ecstasy , and inhalants , as well as indices of gateway and illicit substance initiation , at pretest and at a follow-up assessment 18 months later . RESULTS Intent-to-treat analyses demonstrated significant effects on substance initiation ( marijuana , inhalants , methamphetamines , ecstasy , gateway index , illicit-use index ) , as well as past-year use of marijuana and inhalants , with positive trends for all substances measured . For three outcomes , intervention effects were stronger for higher-risk students than lower-risk students . CONCLUSIONS Community-based implementation of brief universal interventions design ed for general population s has potential for public health impact by reducing substance use among adolescents This study investigated the effects of a smoking prevention program that emphasized refusal skills training on 1730 adolescents in three high schools and six middle schools . Classes within these schools were r and omly assigned to treatment or no-treatment conditions to avoid confounding schools with treatment condition . The effects of attrition on the internal and external validity of the study were examined . Although the results indicated an apparent effect of the program at the 1-year follow-up in deterring continued smoking among those who were smoking at pretest , this result may have been due to a higher rate of attrition among high-rate smokers in the treatment condition than in the control condition . Attrition also affected external validity . Across both conditions , subjects who were smoking at pretest and who were at risk to smoke were more likely to be missing at follow-up . The program did have an effect on the refusal skills of participants and the validity of this effect was not jeopardized by differential attrition In a recent r and omized field trial , Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth- grade adolescents . This article reports effects among ninth- grade at-risk adolescents . Comparisons between at-risk girls in ALERT Plus schools ( basic curriculum extended to ninth grade with five booster lessons ) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use , at-risk drinking , alcohol use result ing in negative consequences , and attitudinal and perceptual factors conducive to drug use . Program-induced changes in perceived social influences , one 's ability to resist those influences , and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use . No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum ( covering seventh and eighth grade s only ) was delivered . Possible reasons for gender differences and implication s for prevention programming are discussed OBJECTIVE To examine the effectiveness of a drug abuse prevention program in reducing the initiation and escalation of smoking in a sample of predominantly minority junior high school girls . METHODS The 15-session prevention program teaches social resistance skills within the context of a broader intervention design ed to promote general personal and social competence skills , and is implemented in the seventh grade . Smoking rates in girls from 29 New York City public schools who received the program ( n = 1,278 ) were compared to smoking rates in a control group of girls ( n = 931 ) who did not . RESULTS Those who participated in the program were less likely to initiate smoking relative to controls , due in part to significant program effects on smoking intentions , smoking knowledge , perceived peer and adult smoking norms , drug refusal skills , and risk taking . Experimental smokers in the intervention group were less likely to escalate to monthly smoking relative to controls , due in part to significant program effects on smoking intentions . CONCLUSION A school-based drug abuse prevention approach previously found to be effective among white youth significantly reduced smoking initiation and escalation among urban minority girls This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes OBJECTIVE To evaluate the impact of a classroom-based , Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents . DESIGN A two-group r and omized control trial with 1,402 male and female students in grade s 9 through 11 from 14 secondary schools in Toronto , Canada . Participants were r and omly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up . The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine ( http://www.smokingzine.org ) integrated into a program that included a paper-based journal , a small group form of motivational interviewing , and tailored e-mails . MAIN OUTCOME MEASURE Resistance to smoking , behavioral intentions to smoke , and cigarette use were assessed at baseline , postintervention , and three- and six-month follow-up . Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time . RESULTS The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months . The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period . CONCLUSION The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months . By providing an accessible and attractive method of engaging young people in smoking prevention and cessation , this interactive and integrated program provides a novel vehicle for school- and population -level health promotion OBJECTIVE To test whether a social network tailored substance abuse prevention program can reduce substance use among high-risk adolescents without creating deviancy training ( iatrogenic effects ) . METHODS A classroom r and omized controlled trial comparing control classes with those receiving an evidence -based substance use prevention program [ Towards No Drug Abuse ( TND ) ] and TND Network , a peer-led interactive version of TND . Students ( n = 541 , mean age 16.3 years ) in 75 classes from 14 alternative high schools completed surveys before and approximately 1 year after curriculum delivery . Past-month use of tobacco , alcohol , marijuana and cocaine were assessed . RESULTS Overall , TND Network was effective in reducing substance use . However , the program effect interacted with peer influence and was effective mainly for students who had peer networks that did not use substances . Students with classroom friends who use substances were more likely to increase their use . CONCLUSIONS A peer-led interactive substance abuse prevention program can accelerate peer influences . For students with a peer environment that supports non-use , the program was effective and reduced substance use . For students with a peer environment that supports substance use , an interactive program may have deleterious effects This paper presents the results of theory-based intervention strategies to increase the adoption of a tobacco prevention program . The adoption intervention followed a series of dissemination intervention strategies targeted at 128 school districts in Texas . Informed by Social Cognitive Theory , the intervention provided opportunities for districts to learn about and model themselves after ' successful ' school districts that had adopted the program , and to see the potential for social reinforcement through the knowledge that the program had the potential to have an important influence on students ' lives . The proportion of districts in the Intervention condition that adopted the program was significantly greater than in the Comparison condition ( P < 0.001 ) . Stepwise logistic regression indicated that the variables most closely related to adoption among intervention districts were teacher attitudes toward the innovation and organizational considerations of administrators . Recommendations for the development of effective strategies for the diffusion of innovations are presented The onset of smoking behavior in adolescents has been described as a process , beginning when children are young . Little empirical evidence is available , however , on the nature and specifics of the onset process in young children . More information is needed about the early stages of smoking onset in order to design interventions for young children and for early triers . The purpose of the present study was to describe several onset-related variables in young girls and boys and to discuss implication s for design ing prevention interventions that target young children . A total of 1,663 5th- grade students completed a question naire assessing smoking behavior , psychosocial characteristics , and perceptions of a " smoker " image . Saliva sample s for cotinine analysis were also collected . Students were classified as either never-triers ( never tried a cigarette ) or early triers ( tried one or more cigarettes ) on the basis of self-reported smoking . Most students who had tried a cigarette were in the early stages of smoking onset , because approximately 30 % had tried one cigarette and less than 10 % had tried a second . Triers versus never-triers differed on their reported images of smokers , and several psychosocial characteristics predicted trying a cigarette and intentions to smoke for boys This study examined the plausibility of the gateway hypothesis to account for drug involvement in a sample of middle school students participating in a drug abuse , prevention trial . Analyses focused on a single prevention approach to exemplify intervention effects on drug progression . Improvements to social competence reduced multiple drug use at 1- and 2-year follow-ups . Specific program effects disrupted drug progression by decreasing alcohol and cigarette use over 1 year and reducing cigarette use over a 2-year period . Controlling for previous drug use , alcohol was integrally involved in the progression to multiple drug use . Subgroup analyses based on distinctions of pretest use/nonuse of alcohol and cigarettes provided partial support for the gateway hypothesis . However , evidence also supported alternate pathways including cigarette use as a starting point for later alcohol and multiple drug use This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components . Thirty-six rural schools were r and omly assigned to 1 of 3 conditions : ( a ) the classroom-based Life Skills Training ( LST ) and the Strengthening Families Program : For Parents and Children 10 - 14 , ( b ) LST only , or ( c ) a control condition . Outcomes were examined 1 year after the intervention posttest , using a substance initiation index ( SII ) measuring lifetime use of alcohol , cigarettes , and marijuana and by rates of each individual substance . Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation . Relative reduction rates for alcohol initiation were 30.0 % for the combined intervention and 4.1 % for LST only All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in a cardiovascular disease risk-reduction trial . Within each district , one school was assigned at r and om to receive a special 20-session risk-reduction intervention and one school served as a control . At a two-month follow-up , risk factor knowledge scores were significantly greater for students in the treatment group . Compared with controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline reported regular exercise at follow-up . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up , while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared with 10.3 % in the control group . Students in the treatment group were more likely to report that they would choose " heart-healthy " snack items . Beneficial treatment effects were observed for resting heart rate , body mass index , triceps skin fold thickness , and subscapular skin fold thickness . The results suggest that it is feasible to provide cardiovascular disease risk-reduction training to a large segment of the population through school-based primary prevention approaches Studies have shown that the effectiveness of programs or curricula may depend in part on who delivers the material . In adolescent health education programs , peer leaders are often recruited to implement programs because they are more persuasive to other adolescents than adults . Teachers also systematic ally vary how groups are constructed in school-based health education programs . This study compared the effects of three leader and group selection methods within the context of two tobacco prevention programs . Eight schools received a social influences program ( Chips ) and eight received a program with a multicultural emphasis ( Flavor ) . Within these 16 schools 84 classrooms consisting of 1486 students were r and omly assigned to one of three leader and group creation conditions : ( i ) leaders defined as those who received the most nominations by students and groups created r and omly ( r and om group ) , ( ii ) same as ( i ) but groups created by assigning students to the leaders they nominated ( network ) , and ( iii ) leaders and groups created by teachers ( teacher ) . One year follow-up data showed that main effects of the curriculum and network assignments were non-significant on smoking initiation when entered alone . Interaction terms of curriculum and assignment methods , however , were significant such that the network and teacher conditions were less effective than the r and om group condition with Chips , and more effective than r and om group condition with Flavor . These data show that school-based prevention programs should be evaluated in light of who implements the program . Even a peer-led program will be differentially effective based on how leaders are selected and how groups are formed , and this effect may be curriculum dependent OBJECTIVE This paper reports the impact of two first- and second- grade classroom based universal preventive interventions on the risk of Suicide Ideation ( SI ) and Suicide Attempts ( SA ) by young adulthood . The Good Behavior Game ( GBG ) was directed at socializing children for the student role and reducing aggressive , disruptive behavior . Mastery Learning ( ML ) was aim ed at improving academic achievement . Both were implemented by the teacher . METHODS The design was epidemiologically based , with r and omization at the school and classroom levels and balancing of children across classrooms . The trial involved a cohort of first- grade children in 19 schools and 41 classrooms with intervention at first and second grade s. A replication was implemented with the next cohort of first grade children with the same teachers but with little mentoring or monitoring . RESULTS In the first cohort , there was consistent and robust GBG-associated reduction of risk for suicide ideation by age 19 - 21 years compared to youths in st and ard setting ( control ) classrooms regardless of any type of covariate adjustment . A GBG-associated reduced risk for suicide attempt was found , though in some covariate-adjusted models the effect was not statistically robust . No statistically significant impact on these outcomes was found for ML . The impact of the GBG on suicide ideation and attempts was greatly reduced in the replication trial involving the second cohort . CONCLUSIONS A universal preventive intervention directed at socializing children and classroom behavior management to reduce aggressive , disruptive behavior may delay or prevent onset of suicide ideation and attempts . The GBG must be implemented with precision and continuing support of teachers OBJECTIVES We present 1-year follow-up data from a school-based tobacco use prevention project design ed to test the effectiveness of three main components of social influence programs . The components teach refusal skills , awareness of social misperceptions about tobacco use , and misconceptions about physical consequences . METHODS Four different curricula were developed and tested in a r and omized experiment involving 48 junior high schools . The outcome variables examined were changes in initial and weekly cigarette and smokeless tobacco use 1 year after the intervention . RESULTS Analyses indicated that each of the component programs were effective in decreasing both the initial and the weekly use of cigarettes except for the curriculum in which refusal skills were taught . Also , each curriculum was effective in decreasing the initial use of smokeless tobacco except for the one aim ed at correcting social misperceptions . Only the combined curriculum showed an effect on the weekly use of smokeless tobacco . CONCLUSIONS The combined intervention was the most effective overall in reducing the initial and weekly use of cigarettes and smokeless tobacco . This suggests that different reasons for use exist and need to be counteracted simultaneously . However , since single programs were also effective in reducing all but weekly smokeless tobacco use , any of these components may be worthwhile prevention tools This study examines the effects of 2 brief family-focused interventions on the trajectories of substance initiation over a period of 6 years following a baseline assessment . The 2 interventions , design ed for general- population families of adolescents , were the 7-session Iowa Strengthening Families Program ( ISFP ) ( Molgaard & Spoth , 2001 ) and the 5-session Preparing for the Drug Free Years Program ( PDFY ) ( Catalano , Kosterman , Haggerty , Hawkins , & Spoth , 1999 ) . Thirty-three rural public schools were r and omly assigned to the ISFP , the PDFY , or a minimal-contact control condition . The authors evaluated the curvilinear growth observed in school-level measures of initiation using a logistic growth curve analysis . Alcohol and tobacco composite use indices -- as well as lifetime use of alcohol , cigarettes , and marijuana-- and lifetime drunkenness , were examined . Significant intervention-control differences were observed , indicating favorable delays in initiation in the intervention groups OBJECTIVE To evaluate the impact of a theatre production on smoking-related attitudes , norms , and intentions of children in grade s 1–6 ( aged 6–12 years ) . DESIGN Seventeen schools were r and omly selected among 160 that were participating in the implementation of the theatre production 2 Smart 2 Smoke . Schools that participated in the theatre production after 3 December 1997 were assigned as control schools . Assignment of schools to a given date for the theatre production was a r and om process . Students in grade s 1–6 were surveyed before and after the theatre production and associated activities . The data were examined for pretest – posttest differences and intervention-control differences . The school was the unit of analysis . SETTING Elementary schools in the Twin Cities metropolitan area . PARTICIPANTS Students in grade s 1–6 in 17 elementary schools . INTERVENTION Two plays2 Smart 2 Smoke for grade s 1–3 ( 6–8 year olds ) and grade s 4–6 ( 9–12 year olds ) , respectively , with follow-up activities for the classroom and home . A national theatre company performed the plays at the schools . MAIN OUTCOME MEASURES Intention to smoke in the future , normative expectations about how many people smoke , functional meanings of smoking , expected outcomes of smoking . RESULTS 10 % more students reported that they would never smoke a cigarette after the theatre production . Students in grade s 4–6 showed changes in the functional meanings and expected outcomes of smoking . Students in grade s 1–3 showed changes in normative expectations . CONCLUSIONS Further research on the impact of live theatre productions as a smoking prevention strategy is recommended Using st and ard missing data taxonomy , due to Rubin and co-workers , and simple algebraic derivations , it is argued that some simple but commonly used methods to h and le incomplete longitudinal clinical trial data , such as complete case analyses and methods based on last observation carried forward , require restrictive assumptions and st and on a weaker theoretical foundation than likelihood-based methods developed under the missing at r and om ( MAR ) framework . Given the availability of flexible software for analyzing longitudinal sequences of unequal length , implementation of likelihood-based MAR analyses is not limited by computational considerations . While such analyses are valid under the comparatively weak assumption of MAR , the possibility of data missing not at r and om ( MNAR ) is difficult to rule out . It is argued , however , that MNAR analyses are , themselves , surrounded with problems and therefore , rather than ignoring MNAR analyses altogether or blindly shifting to them , their optimal place is within sensitivity analysis . The concepts developed here are illustrated using data from three clinical trials , where it is shown that the analysis method may have an impact on the conclusions of the study Summary Background Schools in many countries undertake programmes for smoking prevention , but systematic review s have shown mixed evidence of their effectiveness . Most peer-led approaches have been classroom-based , and rigorous assessment s are scarce . We assessed the effectiveness of a peer-led intervention that aim ed to prevent smoking uptake in secondary schools . Methods We undertook a cluster r and omised controlled trial of 10 730 students aged 12–13 years in 59 schools in Engl and and Wales . 29 schools ( 5372 students ) were r and omly assigned by stratified block r and omisation to the control group to continue their usual smoking education and 30 ( 5358 students ) to the intervention group . The intervention ( ASSIST [ A Stop Smoking In Schools Trial ] programme ) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke . Follow-up was immediately after the intervention and at 1 and 2 years . Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake , which was identified at baseline as occasional , experimental , or ex-smokers . Analysis was by intention to treat . This study is registered , number IS RCT N55572965 . Findings The odds ratio of being a smoker in intervention compared with control schools was 0·75 ( 95 % CI 0·55–1·01 ) immediately after the intervention ( n=9349 students ) , 0·77 ( 0·59–0·99 ) at 1-year follow-up ( n=9147 ) , and 0·85 ( 0·72–1·01 ) at 2-year follow-up ( n=8756 ) . The corresponding odds ratios for the high-risk group were 0·79 ( 0·55–1·13 [ n=3561 ] ) , 0·75 ( 0·56–0·99 [ n=3483 ] ) , and 0·85 ( 0·70–1·02 [ n=3294 ] ) , respectively . In a three-tier multilevel model with data from all three follow-ups , the odds of being a smoker in intervention compared with control schools was 0·78 ( 0·64–0·96 ) . Interpretation The results suggest that , if implemented on a population basis , the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance . Funding MRC ( UK ) We assessed the immediate effects of two universal , first- grade preventive interventions on the proximal targets of poor achievement , concentration problems , aggression , and shy behaviors , known early risk behaviors for later substance use/abuse , affective disorder , and conduct disorder . The classroom-centered ( CC ) intervention was design ed to reduce these early risk behaviors by enhancing teachers ' behavior management and instructional skills , whereas the family-school partnership ( FSP ) intervention was aim ed at improving parent-teacher communication and parental teaching and child behavior management strategies . Over the course of first and second grade s , the CC intervention yielded the greatest degree of impact on its proximal targets , whereas the FSP 's impact was somewhat less . The effects were influenced by gender and by preintervention levels of risk . Analyses of implementation measures demonstrated that greater fidelity to the intervention protocol s was associated with greater impact on behavior ratings and on achievement scores , thus providing some evidence of specificity in the effect of the interventions In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion , University of Bergen started a study of school-based interventions aim ing at preventing smoking among pupils in Norwegian secondary schools . The study comprised a nationwide sample of 4441 students at 99 schools ( 195 classes ) . This panel of students is followed through annual data collection s till they graduate in spring 1997 . Written consensus from students and parents was obtained from 95 % . Schools were systematic ally allocated to one of four groups : Group A , control ; Group B , intervention , containing classroom program , involvement of parents and teacher courses ; Group C , like B , but without teacher courses ; Group D , like B , but without parental involvement . Baseline data were collected by question naires administered in class in November 1994 and the first follow-up survey was carried out in May 1995 . At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A ( control ) and by 1.9 percentage points in Group B ( most extensive intervention ) . As expected , the recruitment of smokers was higher in Groups C and D than in the ideal intervention , but lower than in the control group . Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking , physical maturity , antisocial behavior and parental smoking . The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among ' high-risk ' students than among other students Objective : To assess the effect of an antismoking intervention focusing on adolescents in lower education . Students with lower education smoke more often and perceive more positive norms , and social pressure to smoke , than higher educated students . An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students . Design : Group r and omised controlled trial . Setting : 26 Dutch schools that provided junior secondary education . Subjects : 1444 students in the intervention and 1118 students in the control group , all in the first grade , average age 13 years . Intervention : Three lessons on knowledge , attitudes , and social influence , followed by a class agreement not to start or to stop smoking for five months and a class based competition . Main outcome measures : Comparison of smoking status before and immediately after and one year after the intervention , using multilevel analysis . Results : In the intervention group , 9.6 % of non-smokers started to smoke , in the control group 14.2 % . This leads to an odds ratio of 0.61 ( 95 % CI= 0.41 to 0.90 ) to uptake smoking in the intervention group compared with the control group . One year after the intervention , the effect was no longer significant . Conclusions : In the short-term , an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking . Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents . The results also suggest that additional interventions in later years are needed to maintain the effect Background / Aims : Symptoms of attention deficit hyperactivity disorder ( ADHD ) have often been associated with early-onset smoking . We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking . Methods : In a universal , school-based , r and omized controlled intervention trial , we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use onset among these children at age 10 or 11 years . A sample of 477 first- grade boys and girls were r and omly assigned to the Good Behavior Game intervention ( n = 263 ) , a 2-year ( grade s 2 and 3 ) universal classroom-based intervention aim ed at reducing disruptive behavior problems , or to a control condition ( n = 214 ) . ADHD symptoms were assessed through teacher ratings . Early onset of tobacco use was assessed through self-report . Results : The intervention-induced reductions in ADHD symptoms fully mediated the distal effect of intervention on reductions in early-onset smoking . Conclusions : Our results showed that programs that target ADHD symptoms may protect children from early-onset smoking as well . Further research is needed to examine pathways from ADHD symptoms to tobacco use OBJECTIVES We evaluated the revised Project ALERT drug prevention program across a wide variety of Midwestern schools and communities . METHODS Fifty-five South Dakota middle schools were r and omly assigned to program or control conditions . Treatment group students received 11 lessons in 7th grade and 3 more in 8th grade . Program effects for 4276 8th- grade rs were assessed 18 months after baseline . RESULTS The revised Project ALERT curriculum curbed cigarette and marijuana use initiation , current and regular cigarette use , and alcohol misuse . Reductions ranged from 19 % to 39 % . Program effects were not significant for initial and current drinking or for current and regular marijuana use . CONCLUSIONS School-based drug prevention programs can prevent occasional and more serious drug use , help low- to high-risk adolescents , and be effective in diverse school environments Background To date , no school-based intervention has been proven to be effective in preventing adolescent smoking , despite continuing concern about smoking levels amongst young people in the United Kingdom . Although formal teacher-led smoking prevention interventions are considered unlikely to be effective , peer-led approaches to reducing smoking have been proposed as potentially valuable . Methods / design ASSIST ( A Stop Smoking in Schools Trial ) is a comprehensive , large-scale evaluation to rigorously test whether peer supporters in Year 8 ( age 11–12 ) can be recruited and trained to effect a reduction in smoking uptake among their fellow students . The evaluation is employing a cluster r and omised controlled trial ( RCT ) design with secondary school as the unit of r and omisation , and is being undertaken in 59 schools in South East Wales and the West of Engl and . Embedded within the trial are an economic evaluation of the intervention costs , a process evaluation to provide detailed information on how the intervention was delivered and received , and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group . Schools were r and omised to either continue with normal smoking education ( n = 29 schools , 5562 students ) , or to do so and additionally receive the ASSIST intervention ( n = 30 schools , 5481 students ) . No schools withdrew once the trial had started , and the intervention was successfully implemented in all 30 schools , with excellent participation rates from the peer supporters . The primary outcome is regular ( weekly ) smoking , vali date d by salivary cotinine , and this outcome has been obtained for 94.4 % , 91.0 % and 95.6 % of eligible students at baseline , immediate post-intervention , and one-year follow-up respectively . Discussion Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom . This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools , and how the rigour of such design s can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components PURPOSE Toward developing attractive and effective means to reduce cancer risks faced by Native American people , this study developed and tested interactive computer software to improve dietary choices and prevent tobacco use among Native American adolescents . METHODS Based on a legend of the Seneca Nation , a cancer prevention lesson was developed and programmed for software . A sample of 368 Native American adolescents were divided r and omly into intervention and control arms . Youths in both arms were pre-tested , youths in the intervention arm interacted with the software , and all youths were post-tested . Pre-test and post-test measures covered information and attitudes about cancer risks from dietary practice s and tobacco use . RESULTS Pre-test scores differed between the two arms on youths ' age and on one outcome variable . Relative to their counterparts in the control arm , youths in the intervention arm increased their post-test scores on 8 of 12 outcome measurement variables . Process data gathered during intervention delivery indicated that nearly all youths were involved with the interactive software and lesson . CONCLUSION Interactive computer software holds promise for delivering cancer risk reduction intervention aim ed at modifying dietary habits and preventing tobacco use among Native American youth OBJECTIVES This paper presents up to 5 years post-program outcomes of Project Towards No Drug Abuse ( Project TND ) , a drug abuse prevention program conducted in South California alternative high school system during years 1994 - 1999 . METHODS The effects of a 9-session health motivation -- social skills -- decision-making curriculum were evaluated . Twenty-one schools recruited were r and omly assigned to st and ard care ( control ) , classroom only , or a classroom plus semester-long school-as-community component . Last 30-day use of cigarettes , alcohol , marijuana , and hard drugs were assessed at three time intervals : short-term ( year 1 ) , middle-term ( years 2 or 3 ) , and long-term ( years 4 or 5 ) . Multilevel r and om coefficients modeling were employed to estimate the adjusted levels of substance use . RESULTS Among 1578 baseline subjects , follow-up data were available for 68 % ( year 1 ) , 66 % ( years 2 or 3 ) , and 46 % ( years 4 or 5 ) of subjects , respectively . Results revealed significant positive long-term program effects for hard drug use at year 4 or 5 for the two program interventions ( P = 0.02 ) . CONCLUSIONS Project TND reduced hard drug use in the 46 % who were successfully followed . It is the first program to demonstrate long-term self-reported behavioral effects on hard drug use among high-risk youth by using a school-based , limited-session model A major challenge in the dissemination of evidence -based family interventions ( EBFIs ) design ed to reduce youth substance use and other problem behaviors is effective and sustainable community-based recruitment . This understudied topic is addressed by a preliminary study of 14 community-university partnership teams r and omly assigned to an intervention condition in which teams attempted sustained implementation of EBFIs with two cohorts of middle school families . This report describes attendance rates of recruited families maintained over time and across both cohorts , along with exploratory analyses of factors associated with those rates . When compared with community-based recruitment rates in the literature , particularly for multisession interventions , relatively high rates were observed ; they averaged 17 % across cohorts . Community team functioning ( e.g. , production of quality team promotional material s ) and technical assistance ( TA ) variables ( e.g. , effective collaboration with TA , frequency of TA requests ) were associated with higher recruitment rates , even after controlling for community and school district context ual influences . Results support the community-university partnership model for recruitment that was implemented in the study The aim of this study was to investigate the smoking habits of a sample of second year high school students in Romagna ( Northern Italy ) by means of an anonymous self-administered question naire and the efficiency of a previous health education campaign . A sample of 2,691 16-year-old pupils ( 74 % of the school population of this age ) was r and omly selected . Of these , 863 ( 32.1 % ) had participated in a prevention campaign while attending middle school . 19.1 % of the students who had taken part in the campaign were smokers compared to 23.2 % of those who had not . The students ' smoking habits were found to be influenced by the type of school and by the role models ( parents , siblings , friends , teachers ) . The campaign appears to have had good results , especially in places where it was carried out on a wide scale . Suggestions are made for making such campaigns more efficient OBJECTIVES This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents . METHODS Southern California orthodontic offices were r and omly assigned to experimental ( n = 77 ) and control ( n = 77 ) groups . R and omly selected adolescents were interviewed at baseline and 2 years later ( n = 15,644 ) . Experimental offices received tobacco prevention training , anti-tobacco material s , and 50 cents for each anti-tobacco " prescription " written . RESULTS The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6 % and 12.0 % , respectively ; incidence rates for using tobacco more than 100 times were 7.6 % and 6.8 % . Differences between the groups did not reach significance . Mean prescription compliance was 64.4 % . A multivariate logistic model , showed a significant dose response : patients who received more prescriptions had lower incidence rates than those who received few or none ( 10 % vs 14 % ) . CONCLUSIONS Training , payment , and support did not ensure clinician compliance with prevention services . The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians ' ability to prevent tobacco use To evaluate methods of preventing young children from experimenting with tobacco and to determine cost effectiveness , students ( n = 1005 ) in 31 primary schools , from r and omly selected higher grade -levels were recruited into a partially r and omized , single blinded controlled trial in which seven groups of schools were r and omly assigned to a combination of teaching , leaflet , and drama , in order to modify students ' knowledge , attitudes , beliefs and behaviour ( KAB ) . The eighth group ( n = 346 ) with ten schools , distantly separated from the former , was assigned to be the control , but was dropped from comparison analysis for lack of r and omness at baseline . The mean , st and ard deviation and median age of the intervention groups was 9.94 years ( 0.81 ) , 10.0 years , ( n = 669 ) at baseline ; and 10.62 years ( 0.66 ) , 11.0 years , ( n = 397 ) , at 12 months follow-up . In all , 6.6 % had ever used tobacco at least once at a median age of seven years . Teaching health education at school when combined with other methods was significantly better at improving KAB . In 2003 , after a year post-intervention , the occurrence of experimentation smoking in the last 30 days , dropped from 9.2 % to 1.2 % ( p = 0.00 ) , equivalent to 87 % ( 95 % CI 78 , 93 ) reduction in the group exposed to health education compared to none in the leaflet-only group and Numbers Needed to Treat ( NNT ) = 12.5 . Due to its cost-effectiveness ( comparable to child immunizations ) at BDS dollars 1.89 to 2.89 or US dollars 1 to 1.5 per child contacted and BDS dollars 100 to 140 ( US dollars 50 to 70 ) capital investment in other re sources per school , the experience could be utilized routinely in elementary schools BACKGROUND This study aim ed at exploring the impacts of a school-wide no smoking strategy and a classroom-based smoking prevention curriculum on smoking-related knowledge , attitude , behavior , and skill of junior high school students . METHODS Using a pre-post quasi-experimental design , 469 seventh-to ninth- grade students at four junior high schools in Taiwan , were selected and separated into three groups according to class unit . Experimental group A experienced a school-wide no smoking strategy and a six-session smoking prevention curriculum . Experimental group B experienced only the school-wide no smoking strategy . The control group experienced no intervention . The students were tested 1 week before intervention began and 1 week after it ended . RESULTS Experimental group A exhibited a better underst and ing than either experimental group B or the control group of the dangers of smoking and of techniques for refusing cigarettes ; and in fact , group A indicated low smoking intention than experimental group B. Experimental group A also had a better attitudes towards resisting smoking than the control group . However , the intervention had no demonstrable effect on the smoking behavior and on the smoking substitution methods of students . CONCLUSIONS To reduce the smoking rates among junior high school students , diversified school-wide no smoking strategies and st and ardized , diversified instruments should be adopted so that outcomes of smoking prevention work may be assessed more objective ly and effectively Primary prevention of smoking in adolescents requires effective screening instruments for identifying those adolescents who are most likely to experiment with cigarettes . This study investigated the predictive value of a measure of susceptibility to smoking ( the lack of a firm commitment not to smoke ) for predicting smoking initiation 1 and 2 years later among 687 seventh- grade nonsmokers . Results showed that susceptible adolescents were approximately two to three times more likely to experiment with cigarettes during the ensuing 2 years than were nonsusceptible adolescents . At the lower levels of smoking , these relationships persisted even after controlling for psychosocial variables . Measures of susceptibility to smoking could be an effective tool for identifying adolescents at increased risk of experimenting with cigarettes or assessing their readiness for smoking-prevention programs We reported previously on the success of an innovative approach to cigarette smoking prevention in seventh- grade students . The present report describes a 3-year follow-up of three schools and 1081 sutdents initially involved in the research program . The curriculum emphasizes the shortterm influences which affect smoking in youth , particularly social and peer influences . In the school which received this curriculum from likeaged peer leaders , the incidence of smoking remained low compared to that in a control school . Those who did smoke in this school consumed significantly fewer cigarettes . In the school where the curriculum was adult taught , smoking rates were initially lower but rose in the later years , ultimately differing little from those in the control school . Reported smoking behavior was confirmed by saliva ihiocyanate measurement in all students . Cigarette smoking behavior appears significantly inhibited by a peer-taught curriculum and that effect is retained for several years after the education program BACKGROUND This article discusses the development , implementation , and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States . METHODS The intervention outcome study includes a research design and outcome measurement instruments . In collaboration with Native American communities , reservations , and organizations in the Northeastern United States , implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention . RESULTS Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising , and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest . Youths in the combined intervention were significantly less apt to report smoking of any kind . Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items . As for dietary variables , pretest to posttest measurement scores showed that , after receiving the curriculum , youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implication s of consuming dietary fat , fiber , fruits , and vegetables . Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practice s , cultural dietary habits , and healthy food choices available for Native American cultures . Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions . CONCLUSIONS Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns . In particular , results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths ' knowledge and attitudes with regard to tobacco use and diet . Further , the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum OBJECTIVE To evaluate the process of smoking prevention and control among Chinese adolescent with a model on health promotion in junior high school . METHODS A cluster-r and omized , controlled and schooled-based trial on smoking prevention was conducted among 2343 students at four secondary schools in Huangpu District of Guangzhou . Students ' reports and investigators ' daily records were used to evaluate the intervention measures . RESULTS During the one-year period of intervention ( Dec. 2004 through Dec. 2005 ) , eighteen activities had been implemented among students , teachers , parents and cigarette retailers . Ranked by the rate of awareness , the top six activities were shown as follows : " the nicotine toxicity experiment " ( 90.7 % ) , " agreement of building families free of smoking"(77.7 % ) , " a letter to parents " ( 77.1 % ) , " no-smoking signs " ( 76.5 % ) , " Blackboard information about health and smoking " ( 75.0 % ) , and " signature on the 18th World Day of No Smoking " ( 70.2 % ) . Among all the activities , " the nicotine toxicity experiment " had the highest rate of participation ( 88.5 % ) , followed by " a letter to parents " ( 73.6 % ) , " agreement of building families free of smoking " ( 69.8 % ) , " health education through experiments"(68.6 % ) , " health education through multimedia " ( 65.7 % ) and " signature on the 18th World Day of No Smoking " ( 65.6 % ) . The top seven activities in which students showed greatest interests were " the nicotine toxicity experiment " ( 64.5 % ) , " signature on the 18th World Day of No Smoking " ( 33.0 % ) , " health education through experiments " ( 31.2 % ) , " health education through multimedia " ( 29.8 % ) , " class meetings with a thesis of smoking " ( 26.8 % ) , " health pamphlets " ( 26.6 % ) , " specific textbooks " ( 25.9 % ) . The extent of students ' general satisfaction to the work of tobacco control in school during the last year was 52.4 % . The biggest perceived shortcoming for the intervention plan was the low participation of students . CONCLUSION Some intervention measures had not been fully carried out among the students and only covered part of them . It is necessary to adjust the previous intervention measures through keeping the nicotine toxicity experiment , health education through multimedia and other measures with extensive participation of students and at the same time , to avoid literal material s , exhibition boards and traditional single-way health education program This paper describes a preventive intervention trial called EARLY ALLIANCE which is aim ed at reducing risk for three adverse outcomes in childhood and adolescence : conduct problems , substance abuse , and school failure . The structure of the prevention trial is unique because two linked design s are being implemented concurrently . The primary design focuses on children at elevated risk for adverse outcomes , and compares a targeted , multi context ual preventive intervention with family , classroom , peer relational , and academic components to a universal , schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a " usual care " control condition . The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition . The paper describes the theoretical foundation for EARLY ALLIANCE , the goals of the prevention trial , the rationale for design choices , and the methods employed An 8-month school-based smoking prevention program tested with 1526 seventh grade students result ed in a substantial reduction in the incidence of smoking relative to a comparison population . Two curriculum elements were found to have important deterrent effects on smoking onset : ( 1 ) emphasis on immediate and primarily social consequences of smoking and ( 2 ) personalization of the course material s and mode of presentation to include relevant peer role models and active individual role playing . Thiocyanate analysis of saliva sample s taken from all participants corroborated the validity of self-report measures of smoking behavior This study evaluates the effects of a school-based smoking prevention program after 1 year , using school ( 22 middle/elementary schools , 15 high schools ) as both the unit of r and omization and the unit of analysis . The multi grade level ( grade s 6 through 9 ) intervention was design ed to address comprehensively the social influence factors that encourage smoking . Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education , 5 of which were the sessions design ed for this evaluation , and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education . Thus , the study evaluated the incremental effects of the social influence intervention compared to “ st and ard-care ” curricula . Among those who reported smoking one or more cigarettes in the month prior to the intervention , there was a significant treatment effect on rate of smoking at one year , but no grade level , gender , or interaction effects . The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month , compared to 111.6 cigarettes per month in control schools , a 31.4 % difference . These effects were not accounted for by differential subject attrition . The analyses for nonsmokers , however , showed no significant effects , and the program did not affect self-reported alcohol or marijuana use . Taken together with the results of other prevention studies , these results point to the need for the development and evaluation of new initiatives to prevent substance use This article presents the evaluation of written paragraphs which described twenty-one drug abuse prevention “ themes ” contained in thirty-five separate activities , as part of the process of curriculum development targeting Continuation High School students . The goal was to determine which activities were most preferred by these youth . The paragraphs consisted of descriptions of traditional drug abuse prevention program activities , alternative activities using the themes underlying traditional activities , and novel activities generated from newly developed themes . The study was conducted with seven Continuation High Schools . Three hundred and fifteen students participated in this study . Each student rated detailed written descriptions of five activities . Classrooms were r and omly assigned to different combinations of paragraphs . An analysis of variance indicated that there were significant differences in preferences among activities , with a marked preference for the alternative and novel activity presentations . Females , Latinos , older students , and non-marijuana users rated the activities higher overall . There were no significant interactions between demographic variables and order of activity preference . If there is a limit in amount of allotted time and re sources , the theme study is an appropriate and cost-effective tool for gaining important information for health curricula development This study assessed the immediate and short-term outcomes of adapting a culturally-grounded middle school program , keepin ' it REAL , for elementary school students . After curriculum adaptation , 10 schools were r and omly assigned to the intervention in 5th grade with follow-up boosters in 6th grade ; 13 schools were r and omly assigned to the control condition , implementing the school 's pre-existing substance use prevention programming . Students ( n = 1,566 ) completed a question naire prior to curriculum implementation and follow-up question naires toward the end of 5th and 6th grade . The 5th grade kiR curriculum generally appeared no more effective than the control schools ' programming in changing students ' resistance or decision-making skills ; substance use intentions , expectancies , or normative beliefs ; or lifetime and recent substance use . Such findings have implication s for the age appropriateness of school-based programs BACKGROUND The present study addresses diffusion of a psychosocial-based substance abuse prevention program , including : ( a ) teacher adoption , implementation , and maintenance ; ( b ) teacher characteristics associated with implementation ; ( c ) the relationship between integrity of program delivery and program outcomes ; and ( d ) the effectiveness of teacher training and school principal involvement in increasing implementation . METHODS Participants were teachers ( n = 60 ) , school principals ( n = 25 ) , and fifth- grade students ( n = 1147 ) from four Los Angeles area school districts . Districts were r and omly assigned to an intensive or brief teacher training condition . Schools were r and omly assigned to a principal-intervention or a no-principal-intervention condition . Assessment s included teacher and principal self-reports , classroom observations of program delivery , and evaluation of immediate program outcomes . RESULTS During the first year , 78 % of trained teachers implemented one or more program lessons . During the second year , only 25 % maintained implementation of the program . Implementors reported fewer years of teaching experience and stronger self-efficacy , enthusiasm , preparedness , teaching methods compatibility , and principal encouragement than did nonimplementors . The principal intervention increased rates of implementation , but the intensive teacher training did not . Integrity of program delivery was positively associated with immediate program outcomes . CONCLUSIONS Program implementation was highly variable , suggesting that widespread teacher use of psychosocial-based programs can not be taken for granted . Strategies for increasing implementation and maintenance need to be developed INTRODUCTION AND AIMS Declines in adolescent smoking prevalence have slowed recently , result ing in increased interest and literature in tobacco harm minimisation . To date , harm reduction strategies have focused largely on modifying the product and alternative ( safer ) mechanisms of nicotine delivery . There has been little exploration of primary harm minimisation to prevent the onset of regular smoking among young people . A major concern expressed about harm reduction interventions and young people is that they may increase experimentation among non-users . DESIGN AND METHODS The Smoking Cessation for Youth Project was a 2-year school-based cluster r and omised controlled trial conducted in 30 Western Australian schools . Results on the primary outcome showed a significant reduction in regular smoking among 4636 13 - 15-year-olds receiving a harm minimisaton versus st and ard intervention . This paper addresses the intervention effects on 2078 students who had not smoked at baseline . RESULTS At 20-month follow-up , smoking initiation was slightly lower among intervention students than comparison students ( who received a largely abstinence-based intervention ) , although this difference did not attain statistical significance ( OR=0.86 ; 95 % confidence interval : 0.68 , 1.09 ) . DISCUSSION AND CONCLUSIONS This study provided limited evidence to suggest that harm minimisation is a superior approach to abstinence-based interventions for non-smokers . However , this intervention did not contribute to increased experimentation among non-smokers . Although more trials are required , these results indicate that fears of potential negative iatrogenic effects from school-based harm minimisation interventions may be unwarranted Four years of longitudinal data from 373 families participating in a r and omized intervention-control clinical trial were used to examine whether intervention effects on adolescent alcohol and tobacco use trajectories were moderated by family risk , as defined by parental social emotional maladjustment . Consistent with earlier outcome evaluations based on analyses of covariance , analyses confirmed that both the Preparing for the Drug Free Years program and the Iowa Strengthening Families Program favorably influenced alcohol use index trajectories across the time frame of the study ; only the latter program , however , evidence d positive effects on a tobacco use index . Concerning the primary research question , analyses provided no support for family risk moderation of any intervention effect . Findings indicate the feasibility of developing universal preventive interventions that offer comparable benefits to all families Much research has been done in developing and implementing smoking prevention programs ; however , few studies have focused on urban Black population s. In November of 1989 , a comprehensive prevention program was implemented to decrease the incidence of new smokers within the adolescent population in a Black community . The program combined a school-based curriculum with a comprehensive media intervention . All components of the program were financed by business leaders from the targeted community . There were two experimental conditions : one group participated in a school-based intervention and were prompted to participate in a multi-media intervention and the other group had access to the multi-media intervention ; however , they were not prompted to participate . A key finding was that the rate of smoking decreased for all children involved in the intervention . The authors present a model that can be employed to prevent other high-risk behaviors within the Black population The primary purpose of this study was to test the efficacy of a brief , multi-health behavior intervention integrating physical activity and alcohol use prevention messages for high school-aged adolescents . A total of 604 participants , 335 9th and 269 11th grade students from a suburban high school in northeast Florida participated in this study . A r and omized control trial was conducted with participants r and omly assigned within grade levels to receive either a brief consultation and prescription with a mailed reinforcing follow-up flyer ( Project SPORT ) or a minimal intervention control consisting of a wellness brochure provided in school and a pamphlet about teen health and fitness mailed to the home . Differences between intervention groups were evaluated with a series of MANCOVA tests . Project SPORT participants demonstrated significant positive effects at 3-months postintervention for alcohol consumption , alcohol initiation behaviors , alcohol use risk and protective factors , drug use behaviors , and exercise habits , and at 12-months for alcohol use risk and protective factors , cigarette use , and cigarette initiation ( p 's < 0.05 ) . A post hoc analysis examining interactions between past 30-day use of marijuana and /or cigarettes by treatment group indicates significant positive effects for drug using adolescents who received Project SPORT on alcohol consumption , drug use behaviors , and drug use initiation at 3-months , and for drug use behaviors and exercise habits at 12-months ( p 's < 0.05 ) . A brief , 12-min one-on-one consultation integrating alcohol avoidance messages within those promoting fitness and other positive health behaviors holds promise for influencing adolescent alcohol and cigarette use and other health behaviors at posttreatment and 1 year later . Long-term sustained effects for cigarette and marijuana use , and both vigorous and moderate physical activity , were found among adolescents using marijuana and /or cigarettes prior to intervention Abstract Objective : To assess the net 5 year effects of intervention of a community based demonstration project , the Heartbeat Wales programme , on modifiable behavioural risks for prevention of cardiovascular disease . Design and setting : Quasi-experimental design comparing results from two independent cross sectional population surveys conducted in 1985 and 1990 in Wales and a matched reference area in north east Engl and . Subjects : R and om , stratified sample s of people aged 18 - 64 years ( 18 538 in 1985 and 13 045 in 1990 ) in Wales and in north east Engl and ( 1483 and 4534 , respectively ) . Intervention : A coordinated range of activities for heart health promotion in Wales entailing public education campaigns along with supportive policy and infrastructure change . In the reference area no additional community heart health promotion was planned , though considerable activity did take place , “ contaminating ” the reference area . Main outcome measures : Fifteen self reported behavioural indicators relating to dietary choice , smoking , frequency of exercise , and weight . Results : Positive changes ( for health ) in behavioural outcomes were observed among the population in Wales , including a reduction in reported smoking prevalence and improvements in dietary choice . There was no net intervention effect for the programme over and above observed change in the reference area . Conclusions : No definite conclusions can be drawn concerning the efficacy of the programme in terms of behavioural outcomes . With hindsight , the difficulties of evaluating such a complex multifaceted intervention were underestimated . Further debate on the most appropriate methods for assessing the effectiveness of community based health promotion programmes is called for . Key messages Heartbeat Wales was set up in 1985 as a community based programme to demonstrate risk reduction for cardiovascular disease Important changes were observed in modifiable risks for cardiovascular disease in Wales between 1985 and 1990 There was an unexpectedly rapid uptake of heart health promotion activity in the reference area No net intervention effects were found for the programme over and above changes in the reference area Improvements in methods of evaluation for community based health promotion programmes are The objective of this study was to evaluate the impact of a revised state-of-the-art drug prevention program , Project ALERT , on risk factors for drug use in mostly rural midwestern schools and communities . Fifty-five middle schools from South Dakota were r and omly assigned to treatment or control conditions . Treatment-group students received 11 lessons in Grade 7 and 3 more in Grade 8 . Effects for 4,276 eighth grade rs were assessed 18 months after baseline . Results indicate that Project ALERT had statistically significant effects on all the targeted risk factors associated with cigarette and marijuana use and more modest gains with the pro-alcoholrisk factors . The program helped adolescents at low , moderate , and high risk for future use , with the effect sizes typically stronger for the low- and moderate-risk groups . Thus , school-based drug prevention programs can lower risk factors that correlate with drug use , help low- to high-risk adolescents , and be effective in diverse school environments This study presents one-year follow-up data from an evaluation study testing the effectiveness of a cognitive-behavioral substance abuse prevention approach which emphasizes the teaching of social resistance skills within the larger context of an intervention design ed to enhance general social and personal competence . The follow-up study involved 998 eighth grade rs from 10 suburban New York junior high schools . Two schools were assigned to each of the following conditions ( a ) peer-led intervention , ( b ) peer-led intervention with booster sessions , ( c ) teacher-led intervention , ( d ) teacher-led intervention with booster sessions , and ( e ) control . The original intervention was implemented in the seventh grade ; the booster intervention was implemented during the eighth grade . Results indicate that this type of prevention strategy , when implemented by peer leaders in the seventh grade and when additional booster sessions are provided during the eighth grade , can reduce tobacco , alcohol , and marijuana use . Similar effects are evident for females when the prevention program is implemented with fidelity by classroom teachers . Moreover , the prevention program is also capable of producing a significant impact on several hypothesized mediating variables This article examines the impact of the school-based smoking-prevention program " BE smokeFREE " on adolescent smoking . A national representative sample of 99 schools ( 195 classes , 4,441 students ) was used when the intervention started in November 1994 . Schools were allocated to one of four groups : a comparison group ( A ) and three intervention groups ( B , C , and D ) . Group B received the most comprehensive intervention . A baseline ( autumn 1994 ) and three follow-up data collection s ( 1995 , 1996 , and 1997 ) were conducted . There were no significant differences in smoking habits among the four groups at baseline . The smoking habits in the group that was involved in the most comprehensive intervention ( group B ) changed more favourably than those of students in the comparison schools over the three follow-up data collection s. At the third follow-up , the proportion of students smoking weekly or more in the comparison group was 29.2 % , compared with 19.6 % in the model intervention group . The two less comprehensive interventions ( no teacher in-service courses in group C , and no involvement of parents in group D ) appeared to be less effective than the model intervention . Multilevel multiple logistic regression analyses , comparing changes in smoking habits between students in group B with those among students in the comparison schools , confirm the conclusion that the comprehensive intervention was the most effective . This school-based intervention , based on a social influence approach , proved to be effective at reducing smoking rates among participants This article discusses the findings of Focus Group Discussion s ( FGDs ) that were conducted as a formative assessment for Project MYTRI ( Mobilizing Youth for Tobacco Related Initiatives in India ) , a r and omized , multicomponent , school-based trial to prevent and control tobacco use among youth in India . Forty-eight FGDs were conducted with students ( N = 435 ) in sixth and eighth grade s in six schools in Delhi , India . Key findings include : ( a ) students in government schools reported as “ consumers ” of tobacco , whereas students in private schools reported as “ commentators ” ; ( b ) parents and peers have a strong influence on youth tobacco use ; ( c ) chewing gutkha is considered less harmful and more accessible than smoking cigarettes ; ( d ) schools are not promoting tobacco control activities ; and ( e ) students were enthusiastic about the role government should play in tobacco control . These findings are being used to develop a comprehensive intervention program to prevent and control tobacco use among Indian youth OBJECTIVES This study investigated the secondary prevention effects of a substance abuse primary prevention program . METHODS Logistic regression analyses were conducted on 4 waves of follow-up data from sixth- and seventh- grade baseline users of cigarettes , alcohol , and marijuana taking part in a school-based program in Indianapolis . RESULTS The program demonstrated significant reductions in cigarette use at the initial follow-up ( 6 months ) and alcohol use at the first 2 follow-ups ( up to 1.5 years ) . Models considering repeated measures also showed effects on all 3 substances . CONCLUSIONS Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner As no similar study has been conducted in Italy , the Local Health District ( USL ) of Rozzano ( Milano ) , decided to carry on a r and omized controlled trial on the efficacy of a Smoking Prevention Program . In this article we describe study protocol and give data related to program steps already carried out . A team of four MDs involved in school health and a Health Research consultant were in charge for the study . 1013 students from the second class of the secondary school ( 12y age ) were stratified into four subgroups , according to their risk of becoming a smoker and their teachers smoking status . They were subsequently r and omized ( with blocking ) to two groups : the smoking prevention ( which was based on the Waterloo Smoking Program ) and the cardiovascular risk prevention ( based on an ad hoc program by the USL ) which was the control group . Both interventions consisted in six weekly lessons which were delivered in 37 classrooms ( 777 students or 61 % of all the eligible student population , 72 % of r and omized students ) by an equal number of teacher who voluntarily joined the program , during school hours . A larger number of teachers ( 53 ) formerly joined the program but not all accomplished it . Problems with program planning and delivering are described , together with the criteria which guided this approach In a r and omized controlled trial , we evaluated the effect on tobacco use onset among middle school students of Family Communications ( FC ) activities design ed to mobilize parental influences against tobacco use and Youth Anti-tobacco Activities ( YAT ) design ed to market anti-tobacco norms to adolescents . We conducted a simple , two-condition experimental design in which 40 middle schools , with a prevalence of tobacco use at or above the Oregon median , received , by r and om assignment , either the intervention or no intervention . State , county , and local prevention coordinators around Oregon served as liaisons to schools . To generate interest , staff made presentations to these groups and distributed marketing packets at several conferences . Dependent variables were indices of smoking prevalence and use of smokeless tobacco ( ST ) in the prior month . Additionally , we created an intervention manual so that other communities could replicate this study . The findings suggest that efforts to influence parents to discourage their children ’s tobacco use and efforts to market an anti-tobacco perspective to teens are effective in preventing smoking . The impact of YAT is consistent with experimental and nonexperimental evaluations of media campaigns to influence young people not to smoke BACKGROUND This article reports the results of a 5-year , longitudinal evaluation of the effectiveness of Drug Abuse Resistance Education ( DARE ) , a school-based primary drug prevention curriculum design ed for introduction during the last year of elementary education . DARE is the most widely disseminated school-based prevention curriculum in the United States . METHOD Twenty-three elementary schools were r and omly assigned to receive DARE and 8 were design ated comparison schools . Students in the DARE schools received 16 weeks of protocol -driven instruction and students in the comparison schools received a drug education unit as part of the health curriculum . All students were pretested during the 6th grade prior to delivery of the programs , posttested shortly after completion , and resurveyed each subsequent year through the 10th grade . Three-stage mixed effects regression models were used to analyze these data . RESULTS No significant differences were observed between intervention and comparison schools with respect to cigarette , alcohol , or marijuana use during the 7th grade , approximately 1 year after completion of the program , or over the full 5-year measurement interval . Significant intervention effects in the hypothesized direction were observed during the 7th grade for measures of students ' general and specific attitudes toward drugs , the capability to resist peer pressure , and estimated level of drug use by peers . Over the full measurement interval , however , average trajectories of change for these outcomes were similar in the intervention and comparison conditions . CONCLUSIONS The findings of this 5-year prospect i ve study are largely consonant with the results obtained from prior short-term evaluations of the DARE curriculum , which have reported limited effects of the program upon drug use , greater efficacy with respect to attitudes , social skills , and knowledge , but a general tendency for curriculum effects to decay over time . The results of this study underscore the need for more robust prevention programming targeted specifically at risk factors , the inclusion of booster sessions to sustain positive effects , and greater attention to interrelationships between developmental processes in adolescent substance use , individual level characteristics , and social context Seven thous and one hundred twenty-four members of the Classes of 1985 and 1986 who had participated as seventh grade rs in one of several smoking prevention programs were tracked and surveyed for smoking habits at 5- and 6-year follow-up : participation exceeded 90 % in both cohorts . These data indicated that participants who received seventh- grade interventions based on the social influences model had similar smoking patterns compared to participants in other conditions . This finding supports the call for booster sessions after the initial seventh- grade intervention program . Future follow-up studies will assess whether the earlier benefits associated with the social influences model will translate into measurable differences in adult smoking patterns OBJECTIVE This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents . METHOD Youths ( N = 514 , mean age 11.5 years at recruitment ) were assigned r and omly by community site to receive the CD-ROM intervention , the CD-ROM plus parent intervention , or no intervention . All youths completed pretest , posttest and three annual follow-up measurements . After pretesting , youths and parents received their respective interventions . RESULTS Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes . Over time , youths in all 3 groups reported increased use of alcohol , tobacco and marijuana ; youths who received the interventions reported smaller increases than control youths . At 3-year follow-up , alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths , who , in turn , reported less use than controls . Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1- , 2- and 3-year follow-ups . Marijuana use was lower for youths in either intervention than for controls at 1- , 2- and 3-year follow-ups . Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use . Finally , at the 3-year follow-up , youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group , who , in turn , reported more positive levels of family involvement than youths in the control group . CONCLUSIONS Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents OBJECTIVE To evaluate the long-term efficacy of a school-based approach to drug abuse prevention . DESIGN R and omized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation , the prevention program with videotaped training and no consultation , or " treatment as usual " ( ie , controls ) . Follow-up data were collected 6 years after baseline using school , telephone , and mailed surveys . PARTICIPANTS A total of 3597 predominantly white , 12th- grade students who represented 60.41 % of the initial seventh- grade sample . INTERVENTION Consisted of 15 classes in seventh grade , 10 booster sessions in eighth grade , and five booster sessions in ninth grade , and taught general " life skills " and skills for resisting social influences to use drugs . MEASURES Six tobacco , alcohol , and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables . RESULTS Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls . The strongest effects were produced for individuals who received a reasonably complete version of the intervention -- there were up to 44 % fewer drug users and 66 % fewer polydrug ( tobacco , alcohol , and marijuana ) users . CONCLUSIONS Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco , alcohol , and marijuana use if they ( 1 ) teach a combination of social resistance skills and general life skills , ( 2 ) are properly implemented , and ( 3 ) include at least 2 years of booster sessions This study compared two strategies for preventing cigarette smoking among high-school students . One strategy emphasized social-pressure resistance skills , while the other focused on education about health concerns which are relevant to high-school students . Additionally , the use of same-age peer leaders and the use of familiar models in media presentations were investigated . The results suggest that social-influences resistance training was efficacious in reducing transitions to higher use by those who had previously experimented with cigarettes . Health education was most effective in preventing initial experimentation among those who had not smoked prior to the beginning of the study . Neither program was effective in limiting transitions among those who had gone beyond the experimental stage of smoking , and neither had any effect on encouraging cessation . There were no differences which could be attributed to peer leaders or to familiar media models . During later adolescence , a combined health education and social skills training approach is advocated . It is suggested that while there are some gains by implementing programs during late adolescence , prevention programs targeted at younger students may be more effective generally BACKGROUND This article reports follow-up results during grade 9 for a multisite drug prevention program that curbed both marijuana and cigarette use during junior high . Based on the social influence model of prevention , the curriculum sought to motivate young people against drug use and to teach them skills for resisting pro-drug pressures . METHODS Thirty schools drawn from eight urban , rural , and suburban communities in California and Oregon were r and omly assigned to three experimental conditions , two treatment groups and one control . Students in 20 schools received 11 lessons , 8 during grade 7 and 3 in grade 8 ; in 10 of the treatment schools , older teens assisted an adult teacher in program delivery . Students were pretested prior to the program ( grade 7 ) and post-tested 24 months later ( grade 9 ) . RESULTS Earlier effects on cognitive risk factors ( perceived consequences of drug use , normative beliefs , resistance self-efficacy , and expectations of future use ) persisted through grade 9 in the teen leader schools ; in the condition under which adults taught the lessons without teens , the prior beneficial effects on beliefs largely eroded . All of the earlier effects on actual use disappeared by grade 9 , regardless of who taught the lesions . CONCLUSION Continued reinforcement of earlier lessons may be required to sustain prevention gains through the transition to high school A quasi-experimental , longitudinal study was conducted to test the effectiveness over a 1-year period of a cardiovascular risk reduction program for school-age children . The effectiveness of the program was measured with the children 's knowledge of physiology of the heart and cardiovascular risk factors , their health habits , and their physical measurements . Ninety-eight children between the ages of 9 and 12 years participated in the study . The experimental group received a series of five 40-minute sessions on physiology of the heart , smoking , hypertension , diet , and physical activity . Short-term effectiveness of the program was found for the children 's knowledge of physiology of the heart and smoking . Long-term effectiveness was found for running activity Prior investigations have linked behavioral competencies in primary school to a reduced risk of later drug involvement . In this r and omized prevention trial , we sought to quantify the potential early impact of two developmentally inspired universal preventive interventions on the risk of early-onset alcohol , inhalant , tobacco , and illegal drug use through early adolescence . Participants were recruited as they entered first grade within nine schools of an urban public school system . Approximately , 80 % of the sample was followed from first to eighth grade s. Two theory-based preventive interventions , ( 1 ) a family-school partnership ( FSP ) intervention and ( 2 ) a classroom-centered ( CC ) intervention , were developed to improve early risk behaviors in primary school . Generalized estimating equations ( GEE ) multivariate response profile regressions were used to estimate the relative profiles of drug involvement for intervention youths versus controls , i.e. youth in the st and ard educational setting . Relative to control youths , intervention youths were less likely to use tobacco , with modestly stronger evidence of protection associated with the CC intervention ( RR=0.5 ; P=0.008 ) as compared to protection associated with the FSP intervention ( RR=0.6 ; P=0.042 ) . Intervention status was not associated with risk of starting alcohol , inhalants , or marijuana use , but assignment to the CC intervention was associated with reduced risk of starting to use other illegal drugs by early adolescence , i.e. heroin , crack , and cocaine powder ( RR=0.32 , P=0.042 ) . This study adds new evidence on intervention-associated reduced risk of starting illegal drug use . In the context of ' gateway ' models , the null evidence on marijuana is intriguing and merits attention in future investigations Few studies have examined the long-term efficacy of computer-based smoking prevention and cessation programs . We analyzed the long-term impact of A Smoking Prevention Interactive Experience ( ASPIRE ) , a theoretically sound computer-based smoking prevention and cessation curriculum for high school students . Sixteen predominantly minority , inner-city high schools were r and omly assigned to receive the ASPIRE curriculum or st and ard care ( receipt of the National Cancer Institute 's Clearing the Air self-help booklet ) . A total of 1160 students , 1098 of whom were nonsmokers and 62 smokers at baseline , were included . At 18-month follow-up , among baseline nonsmokers , smoking initiation rates were significantly lower in the ASPIRE condition ( 1.9 % vs. 5.8 % , p < .05 ) . Students receiving ASPIRE also demonstrated significantly higher decisional balance against smoking and decreased temptations to smoke . Differences between groups in self-efficacy and resistance skills were not significant . There was a nonsignificant trend toward improved smoking cessation with ASPIRE , but low recruitment of smokers precluded conclusions with respect to cessation . ASPIRE demonstrated the potential for an interactive multimedia program to promote smoking prevention . Further studies are required to determine ASPIRE 's effects on cessation Objective : To investigate why urban Indian 6th grade rs may be using more tobacco than urban Indian 8th grade rs . Design : Cross-sectional survey of students conducted in the summer of 2004 , as the baseline evaluation tool for a group-r and omised tobacco prevention intervention trial ( Project MYTRI ) . Mixed-effects regression models were used to ( 1 ) examine the relationship between 15 psychosocial risk factors and current use of any tobacco , by grade ; and ( 2 ) examine differences in psychosocial risk factors , by grade . Setting : Thirty-two private ( high socioeconomic status ( SES ) ) and government ( low-mid SES ) schools in two large cities in India ( Delhi and Chennai ) . Subjects : Students in the 6th and 8th grade in these schools ( n = 11642 ) . Among these , 50.6 % resided in Delhi ( v Chennai ) , 61.4 % attended a government school ( v a private school ) , 52.9 % were enrolled in 6th grade ( v 8th ) , and 54.9 % were male ( v female ) . Main outcome measure : Current ( past 30 day ) use of any tobacco , including chewing tobacco ( for example , gutkha ) , bidis , or cigarettes . Result : Almost all psychosocial factors were significantly related to tobacco use , for students in both grade s. Some of the strongest correlates included social susceptibility to and social norms about use . Exposure to tobacco advertising was a strong correlate of tobacco use for 6th grade rs , but not for 8th grade rs . Sixth grade rs scored lower than 8th grade rs on almost all factors , indicating higher risk . Conclusions : The “ risk profile ” of 6th grade rs suggests they would be vulnerable to use and to begin using tobacco , as well as to outside influences that may encourage use The efficacy of prevention programs is typically determined through analysis of covariance . To date , a growth curve modeling approach is not used extensively in program evaluation . However , for longitudinal data there are several advantages to using this approach as compared to methods comparing means at two time points in a piecemeal fashion . In this study , latent growth curve models were used to evaluate the effect of a program on the average level of drug use , rate of change ( growth ) of drug use , and acceleration or deceleration in the rate of change of drug use . The study relied on data from the Adolescent Alcohol Prevention Trial , a r and omized longitudinal drug use prevention program . The program consists of drug use information , resistance skills training , and normative education components . Data regarding cigarette and alcohol use were collected over a 5-year period , grade 7 to grade 11 . Students receiving the normative education program had significantly lower average levels of reported cigarette and alcohol use , lower rates of growth for reported cigarette and alcohol use , and less deceleration of reported levels of cigarette and alcohol use as compared with the control group . Growth curve analysis is a powerful and effective tool with which to model change and program efficacy This paper presents the short-term and long-term results of a r and omized smoking prevention trial . The purpose was to evaluate two smoking prevention programs , a social influence ( SI ) program and a SI program with an additional decision-making component ( SI(DM ) ) . Moreover , the contribution of boosters was assessed as well . Fifty-two schools were r and omly assigned to the SI program , the SI(DM ) program or a control group . Half of the treatment schools were r and omly assigned to the booster condition ; the other half did not receive boosters . Both programs consisted of five lessons , each lasting 45 min , and were given in weekly sessions in grade s 8 and 9 of high schools in the Netherl and s. The most successful program was the SI program with boosters which result ed in a significantly lower increase in smoking rates ( 5.6 and 9.7 % , respectively ) compared to the control group ( 12.6 and 14.9 % , respectively ) at both 12 and 18 months follow-up . The results suggest that boosters can be an effective tool for maintaining or increasing the effectiveness of smoking prevention programs . It is recommended that the SI program with the booster be implemented at the national level , since this intervention showed the greatest behavioral effects The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the largest school-based field trial ever sponsored by the National Institutes of Health . The trial demonstrated positive changes in the school food service and physical education program , as well as in students ' cardiovascular health behaviors . Because the CATCH intervention programs were implemented in 56 schools ( in four states ) that were typical of schools throughout the United States , their reception by schools and degree of implementation provide evidence about their feasibility for schools nationally . Extensive process evaluation data were collected from students , teachers , school food service personnel , and physical education specialists throughout the three school years of the CATCH intervention . Four of the CATCH programs — school food service , physical education , classroom curricula , and home programs — were assessed over the three school years . The process data provide information on participation , dose , fidelity , and compatibility of the CATCH programs in the intervention schools for these programs . High levels of participation , dose , fidelity , and compatibility were observed for the four programs during the 3 school years . CATCH emerges as a model of a feasible multilevel health promotion program to improve eating and exercise behaviors for elementary schools in the United States A five-year intervention study of the effectiveness of the " Know Your Body " program in reducing coronary heart disease risk factors among black students in the District of Columbia , who were in grade s 4 - 6 at baseline , was begun in 1983 . Nine schools were stratified on socioeconomic status and r and omly assigned to control and intervention groups . The " Know Your Body " curriculum focuses on nutrition , fitness , and the prevention of cigarette smoking . At baseline , 1,234 students were eligible for the screening in which the following target risk factors were measured : systolic and diastolic blood pressures , ponderosity index , triceps skinfold thickness , postexercise pulse recovery rate , serum total and high density lipoprotein ( HDL ) cholesterol , and serum thiocyanate . After two years of intervention , results indicated that the program may have had a favorable impact on the following risk factors : systolic and diastolic pressures , HDL cholesterol , ratio of total to HDL cholesterol , fitness ( postexercise pulse recovery rate ) , and smoking . Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking . Blood pressure reduction was associated with decreased ponderosity and improved fitness , and increased HDL cholesterol was associated with decreased ponderosity . These results are consistent with other evaluations of the " Know Your Body " program , suggesting that the program may be effective in reducing chronic disease risk in diverse school population A primary prevention research project is described which tests an intervention model based on cognitive and interpersonal skill enhancement . Thirty-two classrooms of sixth grade students were r and omly assigned to either Program or Control conditions , with Program classrooms receiving a twelve-session cognitive skill development curriculum aim ed at reducing rates of substance use as measured by a drug use survey . Students in Program classrooms showed greater decision-making skills , including the ability to generate alternatives and to consider consequences and risks , greater ability to utilize social networks , and greater underst and ing of group roles , behavior , and alternatives . In addition , Program students reported less use of tobacco in the past year than Control Group students , but no differences between groups were found in use of alcohol , marijuana , or other drugs except for a tendency on the part of Program students to show greater experimentation with alcohol . The effectiveness of the intervention in promoting skill development and factors influencing the impact of the intervention on substance use behavior are discussed BACKGROUND The empirical evidence of effectiveness of many school-based programs against substance abuse is rather weak . The EU-Dap study is a multicenter cluster r and omized community trial ( C RCT ) design ed to evaluate such a program . This paper presents study design and baseline characteristics of the study population . METHODS 170 schools from 9 centers from seven countries ( Austria , Belgium , Germany , Greece , Italy , Spain , Sweden ) , stratified according to average social status in the catchment area , were r and omized to either three variants of the active intervention ( basic curriculum , basic with peer involvement , and basic with parent involvement ) or to a control group . The program under evaluation is based on a comprehensive social influence approach , and was delivered during the scholar year 2004 - 2005 to a population of 12- to 14-year-old students attending junior high school . An anonymous question naire administered before and after the intervention was used to track behavioral and attitudinal changes . RESULTS All in all , we included in the study 143 schools and 7079 students , of which 3547 in the intervention groups and 3532 in the control group . At baseline , 34.9 % of students had smoked cigarettes , 24.7 % had been drunk , and 8.9 % had used cannabis at least once in life . DISCUSSION EU-Dap is the first European multicenter r and omized study to evaluate the effectiveness of a school program targeting tobacco , alcohol and drug use . The baseline assessment showed high prevalence and wide geographical variations of substance use BACKGROUND School-based drug prevention programs have been criticized on method ologic grounds because the unit of analysis is often not the unit of r and omization , thus increasing the likelihood of Type I errors . Application of multilevel analytic strategies appropriately corrects this biasing tendency . This study demonstrates the practical use of such analysis . METHODS Data from 2,370 seventh- grade students participating in a substance use prevention trial were analyzed using a multilevel strategy . We examined the effectiveness of a social pressure resistance training and a normative education ( NORM ) intervention against an information-only control group . RESULTS The NORM condition revealed 1-year program effects for cigarette and marijuana use with individuals as the unit of analysis and only marginal effects with classroom as the unit of analysis . No program effects were found using school as the analysis unit . A multilevel strategy revealed program effects for cigarettes and marijuana with both class and school as grouping levels . The effect for alcohol use was significant at the 2-year follow-up . CONCLUSIONS Interventions establishing conservative drug use norms in classrooms may be an effective strategy in reducing substance use onset among adolescents . Utilization of appropriate analytic strategies is important in the analysis and interpretation of data containing nested structures A five-year intervention study of the feasibility and effectiveness of a program aim ed at the primary prevention of chronic disease was initiated in 1980 among children in 22 elementary schools in the Bronx , New York . Schools r and omly were assigned either to the intervention program or to a control group . The intervention program consists of a curriculum focusing on nutrition , physical fitness , and cigarette smoking prevention . The study population at baseline comprised 2,283 fourth- grade rs . Subjects were eligible at baseline and at one-year follow-up for participation in a medical examination in which the following target risk factors were measured : systolic and diastolic blood pressures , plasma total and high-density lipoprotein ( HDL ) cholesterol , serum thiocyanate , ponderosity index , triceps skinfold thickness , and postexercise pulse recovery rate . After one year of intervention , systolic pressure increased less in the intervention group than among controls . Diastolic pressure decreased in both groups , but more in the intervention subjects than in controls . Total cholesterol decreased in the intervention group while increasing among controls . Significant net changes in the favorable direction also were observed for total cholesterol/HDL cholesterol ratio and for thiocyanate . These observations indicate that it is feasible to implement a school-based program aim ed at the primary prevention of chronic disease . The intervention program appears to have had a favorable effect on several target risk factors . Although the effects were relatively small , intervention programs in schools may prove to be effective in lowering chronic disease risk BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multistate field trial examining the effects of school environment , classroom curricula , and family intervention components in promoting the cardiovascular health of elementary school students . The purpose of this paper is to describe the CATCH tobacco use intervention and measurement , including the adoption of tobacco-free school policies . METHODS In this study , changes in school tobacco use policies and smoking experimentation among students were assessed . Smoking experimentation was measured in all CATCH schools when the students were in their fifth- grade year . A total of 6,527 subjects in 96 schools in California , Louisiana , Minnesota , and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior question naire in Spring 1994 . School tobacco use policy , an important complement to classroom- and home-based prevention efforts , was promoted as part of the CATCH intervention . The degree to which such policy was implemented was measured using surveys of school officials . RESULTS At the end of fifth grade , only 4.8 % of the subjects indicated that they had experimented with tobacco . School intervention condition was not a factor in the prediction of experimentation . Those whose best friend or sibling smoked , or who had ready access to cigarettes in the home , were more likely to have experimented with smoking . In the 3 years of the study , the percentages of tobacco-free schools went up from 49.7 to 76.8 % . Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention , the implementation of the tobacco-free schools ' policies did vary substantially from state to state . Minnesota and Texas , with stronger state laws supporting local policy , had nearly completely smoke-free schools . In spite of a statewide tobacco control initiative , California was slower to implement school policies . Louisiana , which allows local decision making regarding smoking policy , had the most difficulty establishing a policy for all districts . CONCLUSION Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels . Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district BACKGROUND Tobacco use is a significant public health problem in China . Culturally specific smoking prevention programs are needed for Chinese adolescents . This study evaluated a school-based smoking prevention curriculum with a social normative approach developed in the United States for adolescents in urban Wuhan , China . METHODS As a r and omized trial , the intervention was implemented in 1998 with 7th grade students in seven schools with seven matched control schools . Multilevel logistic regression models were used to compare ever and recent ( past-month ) smoking behaviors for the control and program conditions . RESULTS At the 1-year follow-up , smoking had increased more rapidly in the control schools than in the program schools . The odds of baseline nonsmokers initiating smoking did not differ between the program and control groups ( OR=1.08 with 95 % CI=0.71 , 1.64 ) . The program prevented progression to recent smoking among boys who were baseline ever smokers . Among boys who were recent smokers at baseline , the prevention program significantly reduced risk of remaining recent smokers at follow-up ( OR=0.45 with 95 % CI=0.23 , 0.88 ) . CONCLUSIONS This social normative smoking prevention curriculum did not demonstrate a significant primary prevention effect but showed potential for secondary prevention . Culturally specific smoking prevention programs are needed for Chinese adolescents OBJECTIVE To evaluate the effectiveness of the school-based drug abuse prevention program developed in the EU-Dap study ( EUropean Drug Abuse Prevention trial ) in preventing the use of tobacco , alcohol and drugs at the post-test . METHODS Cluster R and omised Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . A pre-test survey assessing past and current substance use was conducted before the implementation of the program . The program consisted in 12-hour class-based curriculum based on a comprehensive social-influence approach . A post-test survey was carried out in all participating schools , 3 months after the end of the program . The association between program condition and change in substance use at post-test was expressed as adjusted Prevalence Odds Ratio ( POR ) , estimated by multilevel regression model . RESULTS Program effects were found for daily cigarette smoking ( POR=0.70 ; 0.52 - 0.94 ) and episodes of drunkenness in the past 30 days ( POR=0.72 ; 0.58 - 0.90 for at least one episode , POR=0.69 ; 0.48 - 0.99 for three or more episodes ) , while effects on Cannabis use in the past 30 days were of marginal statistical significance ( POR=0.77 ; 0.60 - 1.00 ) . The curriculum was successful in preventing baseline non-smokers or sporadic smokers from moving onto daily smoking , but it was not effective in helping baseline daily smokers to reduce or stop smoking . CONCLUSION School curricula based on a comprehensive social-influence model may delay progression to daily smoking and episodes of drunkenness BACKGROUND The effectiveness of school-based tobacco use prevention programs depends on proper implementation . This study examined factors associated with teachers ' implementation of a smoking prevention curriculum in a cluster r and omized trial called Project SPLASH ( Smoking Prevention Launch Among Students in Hawaii ) . METHODS A process evaluation was conducted and a cross-condition comparison used to examine whether teacher characteristics , teacher training , external facilitators and barriers , teacher attitudes , and curriculum attributes were associated with the dose of teacher implementation in the intervention and control arms of the study . Data were collected from a total of 62 middle school teachers in 20 public schools in Hawaii , during the 2000 - 2001 and 2001 - 2002 school years . Sources included teacher question naires and interviews . Chi-square test and t test revealed that implementation dose was related to teachers ' disciplinary background s and skills and student enjoyment of the curriculum . RESULTS Content analysis , within case , and cross-case analyses of qualitative data revealed that implementing the curriculum in a year long class schedule and high teacher self-efficacy supported implementation , while high perceived curriculum complexity was associated with less complete implementation . CONCLUSIONS The results have implication s for research , school health promotion practice , and the implementation of evidence -based youth tobacco use prevention curricula Smoking-prevention programs , run by both teachers , and teachers and peers , have been introduced into school curricula in many parts of the world . This paper describes a long-term follow-up of a r and omised controlled trial of a smoking education program for children conducted in Western Australia . Seven years after the first survey of 2,366 Year 7 students in 1981 , 68 per cent of initial participants were traced through public records ; 53 per cent of these responded to a new survey concerning smoking . Previous follow-up after one and two years had shown that both teacher-led and peer-led programs continued to reduce the taking up of smoking by girls to about the same degree , whereas in boys , the teacher-led program appeared to be effective after one year but neither program was effective after two years . In nonsmoking girls , both the intervention programs maintained their effects at the seven-year follow-up , with an almost 50 per cent reduction in smoking prevalence in the intervention group . Nonsmoking girls appeared to respond to cigarette advertisements . Mothers seemed to influence nonsmokers of both sexes and brothers seemed to influence smokers of both sexes . The seven-year follow-up confirmed the results seen at two years for boys , that the effects of the education program had dissipated . However , this study suggests that the smoking-prevention program had a lasting effect on preventing girls from taking up smoking This paper reports six-year follow-up data from the first large-scale r and omized trial of the social influences approach to smoking prevention . In 1979 , 22 schools were r and omly assigned to program or control conditions . Students in program schools received a social influences curriculum in six core and two maintenance sessions in grade 6 , two booster sessions in grade 7 , and one booster session in grade 8 . All students were assessed at pretest ( T1 ) , immediate posttest ( T2 ) , end of grade 6 ( T3 ) , beginning and end of grade 7 ( T4 and T5 ) , end of grade 8 ( T6 ) , and grade s 11 and 12 ( T7 and T8 ) . Ninety percent of study students were relocated and data obtained from over 80 percent of them at T8 . Program effects on experimental smoking observed in grade s 7 and 8 had completely decayed by T8 , six years after the beginning of the program . Grade 6 smoking experience and social risk were each strong predictors of T8 smoking behavior . Subjects who had left school were smoking at more than twice the rate of subjects still in high school ( grade 12 ) at T8 . We discuss implication s of the results Because preschoolers and first grade rs show signs of readiness to try smoking and because they are already learning about smoking through their environment , smoking prevention at the preschool level is appropriate . The large numbers of children seen in primary care practice s and day care facilities are indicative of the numbers that could be exposed to smoking prevention instruction through these setting s. This study assessed the future expectations of children to protect themselves from sidestream smoke after participating in a preschool smoking prevention program offered in four primary care setting s. Through this program , children and their parents read stories and complete activities concerning the human body and the health risks of smoking . Using a r and omized posttest-only case control design , the authors found that children who were exposed to the curriculum were more than twice as likely as others to report the intention to act to protect themselves from adult sidestream smoke A six-year intervention study of the feasibility and effectiveness of a program aim ed at the primary prevention of coronary heart disease ( CHD ) has been initiated among children in six school districts in Westchester County , New York . Schools r and omly were assigned either to the intervention program or to a control group . The intervention program consists of a curriculum focusing on nutrition , physical fitness , and cigarette smoking prevention . The study population at baseline comprised 1,822 fourth- grade rs . This paper presents the findings at baseline and at one-year follow-up for the following target risk factors : systolic and diastolic blood pressure , plasma total and high-density lipoprotein ( HDL ) cholesterol , serum thiocyanate , ponderosity index , triceps skinfold thickness , and postexercise pulse recovery rate . After one year of intervention , the program was found to be acceptable to school administrators , teachers , parents , and children . Small net changes in the favorable direction were observed for diastolic blood pressure and thiocyanate . Intervention programs in schools may , after sufficient duration , prove to be effective in lowering CHD risk School health educators have devoted much attention to cigarette smoking . Recent years have seen the testing of interventions to prevent smoking . To date , controlled studies have not evaluated the added value of skills methods for preventing smoking . This article describes such an evaluation with sixth- grade students from two schools . Subjects were pretested and r and omly assigned to receive conventional health education methods or to receive skills intervention . Both conditions included films , peer testimonials , discussion s , and homework . Health education condition subjects additionally participated in oral quizzes , games , and debates . Skills condition subjects additionally learned problem-solving , self-instruction , and interpersonal communication methods . At postintervention , skills condition subjects , more than health education condition subjects , had better scores on measures of smoking-related knowledge , attitudes , and intentions . In addition , reported cigarette use , vali date d by biochemical data collection , was lower in the skills condition than in the health education condition at all postintervention measurements , including a 24-month follow-up . The article discusses the strengths , limits , and implication s of the study for other smoking prevention efforts in schools Smoking prevention programs based on social influences have reduced smoking prevalence among youth . However , these effects have not been replicated consistently . It is possible that individuals and population s with different dispositional and behavioral characteristics will experience different program effects . This study explored a possible moderation of program effect by comorbidity between depression and smoking ( CoM ) . Data for this analysis were from 2,450 seventh- grade youth ( 51 % boys ) who participated in the Wuhan ( China ) Smoking Prevention Trial ( WSPT ) . WSPT was a r and omized , controlled , 14-session , middle-school-based smoking prevention trial . Baseline and 1-year follow-up surveys were administered . The moderation effect between the program and CoM was tested on 1-year change in recent smoking . The CoM indicator was defined dichotomously as monthly cigarette use and high in depression level ( among the top 20 % in the sample ) . At baseline , a total of 26 girls and 60 boys were identified to have CoM. Among boys ( but not girls ) , CoM significantly moderated the program effect on recent smoking ( p = .01 ) . The program effect among boys with CoM was 4.17 ( 95 % CI 1.47 - 11.76 ) times larger than those without CoM. Among boys with CoM , the odds ratio of recent smoking was 0.18 ( 95 % CI 0.06 - 0.55 ) for program vs. control condition . Among those without CoM , the program did not reduce the odds of recent smoking significantly ( OR = 0.74 , 95 % CI 0.37 - 1.48 ) . The study demonstrated that smoking prevention program effects can vary with individual characteristics , in this case comorbidity between depression and smoking . These findings may help explain the inconsistency in program effects across studies and population s. The findings also may contribute to the design of future programs to address the needs of defined population s and individuals with specific characteristics This r and omized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools ( HPS ) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales , Australia . Pre-test surveys were completed by students in the first 2 years of secondary school , with a 2-year post-test survey . Multivariate analyses examined intervention effect for the main outcome , post-test smoking behavior , controlling for pre-test smoking status , school and other confounders . The sample comprised the cohort of 1852 students who completed both surveys . The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years ( equal increase of 10 % in both groups ) . The program was successful in improving smoking knowledge , but not attitudes , in intervention versus control group ( P < 0.001 ) . Independent predictors of post-test smoking included : pre-test smoking [ odds ratio ( OR ) = 5.44 ; 95 % confidence interval ( CI ) = 3.20 - 9.28 ] , being female ( OR = 0.55 ; CI = 0.35 - 0.87 ) , having more close friends who smoked ( OR = 1.42 ; CI = 1.33 - 1.52 ) , peer group having no clear opinion about smoking ( OR = 3.23 ; CI = 1.27 - 8.27 ) , having more positive and less negative attitudes towards smoking , and being less involved in school activities . We discuss method ological issues in multicomponent community-based interventions , and highlight the strengths and limitations of this study A smoking prevention project in six European countries ( European Smoking prevention Framework Approach ) was developed , featuring activities for adolescents , schools and parents , including out-of-school activities . Consensus meetings result ed in agreement between the countries on goals , objectives and theoretical methods . Countries ' specific objectives were also included . National diversities required country-specific methods to realize the goals and objectives . The community intervention trial was used as the research design . Since interventions took place at the community level , communities or regions were allocated at r and om to the experimental or control conditions . Complete r and omization was achieved in four countries . At baseline , smoking prevalence among 23 125 adolescents at the start of the project was 5.6 % for regular smoking and 4.0 % for daily smoking . Smoking prevalence rates were higher among girls than boys in all countries as far as weekly smoking was concerned . Process evaluations revealed that the project 's ambitions were high , but were limited by various constraints including time and delays in receiving funds . Future smoking prevention projects should aim to identify the effective components within the social influence approach as well as within broader approaches and on reaching sustained effects This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana OBJECTIVES This paper describes the one-year outcomes of the fourth experimental trial of Project Towards No Drug Abuse . Two theoretical content components of the program were examined to increase our underst and ing of the relative contribution of each to the effectiveness of the program . METHODS High schools in Southern California ( n=18 ) were r and omly assigned to one of three conditions : cognitive perception information curriculum , cognitive perception information+behavioral skills curriculum , or st and ard care ( control ) . The curricula were delivered to high school students ( n=2734 ) by project health educators and regular classroom teachers . Program effectiveness was assessed with both dichotomous and continuous measures of 30-day substance use at baseline and one-year follow-up . RESULTS Across all program schools , the two different curricula failed to significantly reduce dichotomous measures of substance use ( cigarette , alcohol , marijuana , and hard drugs ) at one-year follow-up . Both curricula exerted an effect only on the continuous measure of hard drug use , indicating a 42 % ( p=0.02 ) reduction in the number of times hard drugs were used in the last 30 days in the program groups relative to the control . CONCLUSIONS The lack of main effects of the program on dichotomous outcomes was contrary to previous studies . An effect on an ordinal count measure of hard drug use among both intervention conditions replicates previous work and suggests that this program effect may have been due to changes in cognitive misperception of drug use rather than behavioral skill Recent evaluations of smoking prevention programs have suggested considerable promise for curricula emphasizing resistance of social influences . The present study extends these evaluations by addressing key method ological limitations in previous work . Twenty-two matched schools were r and omized to experimental and control conditions . Grade 6 students received a 6-week core curriculum , plus additional sessions through Grade s 7 and 8 . Question naires , and saliva sample s to vali date self-reported smoking behavior , were collected at five times over the 2-year study period . Cross-sectional and longitudinal analyses examined program impact for five levels of initial smoking experience , ranging from “ never smoker ” through regular , weekly smoker . Significant program effects were documented , most clearly for those having some experience with smoking before the program began and for those with smoking peer and family models . This study provides the method ologically most rigorous test to date of social influence programs for smoking prevention and documents for the first time significant effects for those at high risk for smoking OBJECTIVE To test whether baseline data from a r and omised clinical trial are predictive of initiation of tobacco use over a two-year follow-up interval , and to discuss results in the context of a theoretical model . DESIGN Secondary , non-experimental analyses of data collected from a prospect i ve cluster-r and omised clinical trial comparing an intervention with a control condition for reduction of tobacco incidence rates . Orthodontic offices in southern California were recruited and r and omised to an experimental or control group . Patient participants were sample d within each office , and completed a short survey , repeated two years later . SUBJECTS 13,923 patients , 11 - 18 years of age , r and omly sample d from each office . MAIN OUTCOME MEASURES The ability of baseline data to predict initiation of tobacco use over the two-year follow-up interval was tested through a series of logistic regression models . Significant predictors and their interactions were identified in fixed-effects models , and verified in a mixed-effects logistic regression model to account for cluster r and omisation . RESULTS Clinician advice against tobacco use was associated with a lower rate of tobacco use initiation among young people whose peer group considered smoking socially desirable . Rates of initiation increased with age , but this association differed by gender and by whether the adolescent had been offered tobacco within 30 days prior to the baseline assessment . People from minority groups were less likely to initiate tobacco use than whites , and young people engaging in other risk practice s were more likely to initiate tobacco use . CONCLUSIONS Findings support predictions based on learning theory that social processes are critical in the development of health-risk behaviours . Future preventive efforts should target changing the density with which young people encounter pro- and anti-tobacco prompts and consequences in the community The life-skills approach to smoking prevention was tested in this study . In total , 1024 pupils ( mean age 11.4 years , SD = 0.90 ) from Austria , Denmark , Luxembourg and Germany were recruited as an experimental group , and a sample of 834 matched pupils served as a control group . While the pupils from the control group received no specific intervention , the pupils in the experimental group participated in an intervention programme which was based on the life-skills approach and consisted of 21 sessions . The aims of the programme were to promote fundamental social competencies and coping skills . In addition , specific information on cigarette smoking was given and skills for resisting social influences to smoke were rehearsed . The programme was conducted by trained school teachers during a course of 4 months . Anonymous question naires were administrated ( 1 ) before the programme was implemented and ( 2 ) 15 months after the programme had started . Teachers as well as pupils showed a high level of satisfaction with the programme idea and the material s. With regard to the outcome variables , the programme had no differential effect on current smoking ( 4-week prevalence ) . The programme showed a weak effect ( P < 0.1 ) on lifetime smoking prevalence and experimental smoking . There was also an effect of the programme on smoking knowledge , on the social competences of the pupils as well as on the classroom climate . No effects were found on susceptibility to smoking among never-smokers , attitudes towards smoking and the perceived positive consequences of smoking . The results indicate that prevention programmes that are run for only a few months can have a positive impact on variables considered to be protective with regard to smoking uptake OBJECTIVE To determine the efficacy of a spit tobacco ( ST ) intervention design ed to promote ST cessation and discourage ST initiation among male high school baseball athletes . METHODS This study was a cluster-r and omized controlled trial . Forty-four r and omly selected high schools in rural California were r and omized within strata ( prevalence of ST use and number and size of baseball teams ) to either the intervention or the control group . Ninety-three percent of eligible baseball athletes participated , yielding 516 subjects in 22 intervention schools and 568 subjects in 22 control schools . Prevalences of sustained ST cessation and ST use initiation over 1 year were assessed by self-report . Multivariate logistic regression models for clustered responses were used to test the null hypotheses of no association between group and the two outcomes , adjusted for the stratified design and baseline imbalances between groups in significant predictors of ST use . RESULTS Prevalence of cessation was 27 % in intervention high schools and 14 % in control high schools ( odds ratio (OR)=2.29 ; 95 % confidence interval ( CI ) , 1.36 - 3.87 ) . The intervention was especially effective in promoting cessation among those who , at baseline , lacked confidence that they could quit ( OR=6.4 ; 95 % CI , 1.0 - 4.3 ) , among freshmen ( OR=15 ; 95 % CI , 0.9 - 260 ) , and among nonsmokers ( OR=3.2 ; 95 % CI , 0.9 - 11 ) . There was no significant difference between groups in the prevalence of ST initiation . CONCLUSIONS This intervention was effective in promoting ST cessation , but was ineffective in preventing initiation of ST use by nonusers A quasiexperimental study was conducted to explore the efficacy of the program Stay Away from Tobacco ( SAFT ) . Participants -from 11 classes with 381 students total in grade s 7 , 8 , 10 , and 11-were assigned by class to three groups ( intervention group T with school teachers delivering the program , intervention group R with research ers delivering the program , and comparison group C ) . Data were collected at baseline , immediately after the intervention , and 6 months after the intervention . Self-reported smoking was the outcome measure . The 30-day smoking prevalence in group C increased from 4 % at baseline to 10 % at the 6-month follow-up , whereas this rate declined from 11 % to 6 % in group T , and from 9 % to 1 % in group R. For group T , the odds ratio ( for 30-day smoking ) and the regression coefficient ( for indexed number of cigarettes smoked ) assessing interactions between intervention and time were 0.20 ( p < .001 ) and -.1605 ( p < .05 ) , respectively . The same statistics for group R were 0.09 ( p < .001 ) and -.2406 ( p < .01 ) , respectively . The predicted smoking rate declined by 19 % from baseline to 6-month follow-up in group T ( 11.5 % vs. 9.3 % ) , and the same rate declined by 26 % in group R ( 11.1 % vs. 8.2 % ) . The results from this pilot trial suggest that SAFT can reduce cigarette smoking among middle and high school students through its effect on improving these students ' refusal skills and changing their perceived mental and physical values from smoking . A full-scale evaluation is recommended BACKGROUND Antisocial personality disorder ( ASPD ) , violent and criminal behavior , and drug abuse disorders share the common antecedent of early aggressive , disruptive behavior . In the 1985 - 1986 school year teachers implemented the Good Behavior Game ( GBG ) , a classroom behavior management strategy targeting aggressive , disruptive behavior and socializing children to the student role . From first through seventh grade the developmental trajectories of 2311 students from 19 Baltimore City Public Schools were examined . We report the GBG impact on these trajectories and ASPD and violent and criminal behavior by age 19 - 21 . METHODS In five urban , poor to lower middle class predominately African-American areas , three to four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a reading achievement program , or ( 3 ) the st and ard program . Classrooms and teachers were r and omly assigned to intervention or control . Measures at 19 - 21 included self reports and juvenile court and adult incarceration records . GBG impact was assessed via General Growth Mixture Modeling based on repeated measures of aggressive , disruptive behavior . RESULTS Three trajectories of aggressive , disruptive behavior were identified . By young adulthood , GBG significantly reduced the rates of ASPD and violent and criminal behavior among males in the persistent high aggressive , disruptive trajectory . REPLICATION : A replication was implemented with the following cohort of first- grade children using the same teachers , but with diminished mentoring and monitoring . Beneficial impact was found among persistent high males through seventh grade . By young adulthood GBG effects on ASPD and violent and criminal behavior were non-significant , but generally in the hypothesized direction The purpose of this article is to present the intermediate results for Project MYTRI , a school-based , multiple component intervention design ed to prevent and reduce many forms of tobacco use ( chewing tobacco , cigarettes , and bidis ) among youth in India . The intervention is based on effective models in the United States “ translated ” for use in this context . The intervention targets two cohorts of students who were in the 6th and 8th grade when the study started . Thirty-two schools in Delhi ( north India ) and Chennai ( south India ) were r and omized to receive the intervention ( n = 16 ) or serve as a delayed intervention control ( n = 16 ) . Students in these schools were surveyed before the intervention began and at an intermediate point , 1 year into this 2-year intervention ( n = 8,369 ) . A test of the changes in risk factors for tobacco use between the baseline and intermediate surveys revealed that , compared with the control , students in the intervention condition ( a ) had better knowledge about the health effects of tobacco ( P < 0.01 ) ; ( b ) believed that there were more negative social consequences to using tobacco ( P = 0.04 ) ; ( c ) had fewer reasons to use tobacco ( P < 0.01 ) ; ( d ) had more reasons not to use tobacco ( P = 0.03 ) ; ( e ) were less socially susceptible to chewing ( P = 0.04 ) and smoking ( P = 0.03 ) tobacco ; ( f ) perceived fewer peers and adults around them smoked ( P < 0.01 ) or chewed ( P < 0.01 ) tobacco ; ( g ) felt that tobacco use was not acceptable , especially among their peers ( P < 0.01 ) ; ( h ) were more confident in their ability to advocate for tobacco control ( P = 0.03 ) ; ( i ) were more knowledgeable about tobacco control policies ( P < 0.01 ) ; and ( j ) supported these policies , too ( P = 0.04 ) . Fewer students in the intervention condition reported having intentions to smoke tobacco in the next year ( P = 0.02 ) or chew tobacco when they reached college ( P < 0.01 ) . No changes in actual tobacco use were observed at this stage of the study . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1050–6 Five hundred and eleven fourth , fifth , and sixth grade students and their parents from six schools in northwest Arkansas participated in this study . Students were blocked on school and grade level , then assigned r and omly by class to either the intervention Keep A Clear Mind ( KACM ) program or a waiting list control . KACM students received four weekly correspondence lessons design ed to be completed at home with a parent . KACM students reported significantly less perceived peer use of alcohol , tobacco , and marijuana , as well as significantly less peer pressure susceptibility to experiment with cigarettes . Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs , and significantly greater discussion s with their children regarding how to resist peer pressure to use alcohol , tobacco , and marijuana . Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco , and significantly greater motivation to help their children avoid drug use . No significant differences were found between groups on student intentions to use drugs . These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication OBJECTIVES To study if receptivity and exposure to tobacco marketing are correlated with tobacco use and psychosocial risk factors for tobacco use among a sample of urban Indian youth . METHODS Analysis of cross-sectional survey data from Project MYTRI , a group r and omized intervention trial , in Delhi and Chennai , India , collected from sixth and eighth grade rs ( n=11,642 ) , in 32 schools in 2004 . RESULTS Exposure to tobacco advertisements and receptivity to tobacco marketing were significantly related to increased tobacco use among students . CONCLUSION This association suggests the need to strengthen policy and program-based interventions in India to reduce the influence of such exposures Tobacco intervention studies that employ a community trial design require adjustment to the usual analytic methods to account for the allocation of intact social groups to study conditions and the positive intraclass correlation ( p ) that is inevitable in such a design . In the absence of valid estimates of the relevant p , investigators seeking to establish an appropriate sample size could only guess about the magnitude of the problem . We recently published estimates of p for common measures of adolescent tobacco use , but those estimates were unadjusted for potential covariates and so represented an upper limit on the magnitude of p. This report demonstrates how estimates of intraclass correlation may be substantially reduced through regression adjustment for easily measured covariates . Results show that both the p and the residual variance can be reduced , by an average of 20 and 11 % , respectively , offering greater efficiency for investigators who plan future studies and who are able to measure those covariates in their studies . Future work should seek both to replicate this work and to extend it ; for example , to cohort design s where the improvements might be even greater " I do n't smoke , and you ? " is a project aim ed at secondary school students and is part of a wider project called " Free from Smoke " , implemented by the Lombardia Region and involving elementary and secondary school students . The project is a controlled non r and omized study whose aim is to direct students toward a healthy and smoke-free way of living , by also involving parents and teachers . A total of 11,610 12 year-olds of both sexes were evaluated , 6392 of whom were enrolled in the program and 5218 of whom served as controls and only completed the question naire . Three years after the start of the program , a greater increase in the prevalence of smokers was found amongst the group of controls than amongst the enrolled group ( 108,3 % vs + 93.8 % , p>0.001 ) . The percentage of students who believe that smoking even a small number of cigarettes is harmful , increased in the enrolled group ( + 0.6 % ) while it diminished in controls ( -2.1 % ) . In addition , a strong association was found between receiving a weekly allowance and smoking habits . In conclusion , positive results were obtained as regards the prevalence of smokers and the perceived risk of smoking ; however parents ' attitude towards smoking and the availability of a weekly allowance were found to have a strong influence in students ' smoking habits Eighth , ninth and tenth grade rs ( N = 281 ) from two schools in suburban New York participated in a study to test the efficacy of a 10-session comprehensive psychosocial smoking prevention program . Schools were r and omly assigned to experimental and control conditions . All students were given a pretest , posttest and three-month follow-up which assessed smoking behavior as well as knowledge and personality variables . There were significantly fewer new " smokers " in the experimental school than in the control school at both the initial posttest ( p less than .01 ) and the three-month followup ( p less than .05 ) along with significantly greater changes on some of the knowledge and personality variables . Overall , these results support the use of a smoking prevention strategy that focuses on the main psychosocial factors promoting the onset of cigarette smoking by teaching students basic coping skills BACKGROUND The transtheoretical model ( TTM ) and computer technology are promising technologies for changing health behavior , but there is little evidence of their effectiveness among adolescents . METHOD Four thous and two hundred twenty-seven Year 9 ( ages 13 - 14 ) pupils in 26 schools were r and omly allocated to control and 4,125 in 26 schools were allocated to TTM intervention . TTM pupils received three whole class lessons and three sessions with an interactive computer program . Control pupils received no special intervention . Positive change in stage and smoking status was assessed from a question naire completed at baseline , 1 year , and 2 years . R and om effects logistic regression was used to compare the change in stage and smoking status between the arms . RESULTS Eighty-nine percent of the TTM group and 89.3 % of the control group were present at 1-year and 86.0 and 83.1 % , respectively , were present at 2-year follow-up . The adjusted odds ratio ( 95 % confidence interval ) for positive stage movement in the TTM relative to control was 1.13 ( 0.91 - 1.41 ) at 1 year and 1.25 ( 0.95 - 1.64 ) at 2 years and for regular smoking was 1.14 ( 0.93 - 1.39 ) at 1 year and 1.06 ( 0.86 - 1.31 ) at 2 years . Subgroup analysis by initial smoking status revealed no benefit for prevention or cessation . CONCLUSIONS The intervention was ineffective A two-year primary prevention program for junior high school students was evaluated . The program consisted of drug education , " alternatives , " and affective in- service training for the students ' teachers . Students in one junior high school received the intervention and students in another school served as a no-treatment control group . The students were pretested at the beginning of 7th grade and posttested at the end of 8th grade . Positive effects were found for females on several drug-related variables ; few effects were found for males . The findings are discussed with regard to the individual prevention strategies OBJECTIVE To evaluate a secondary school smoking prevention program in a small rural Norwegian municipality . DESIGN The project applied grade specific intervention strategies to all students grade s 6 - 9 and comprised a total of 32 lessons over a period of 3 years , with high student activity . A non-r and omised control group was constituted by all 6th-9th grade students in municipalities of similar characteristics in the same county . Results were recorded in annual class-based surveys . SUBJECTS The intervention group totalled 187 and the control group 364 students . MAIN OUTCOME MEASURES Prevalence of daily and occasional smoking and number of cigarettes smoked , during the intervention period . RESULTS An 80 % lower rate of daily smoking and 50 % fewer cigarettes smoked by daily smokers . Lower rates of smoking in 9th grade occurred mostly among girls . CONCLUSION The project result ed in a lower recruitment of daily smokers up to grade 9 , as well as fewer cigarettes smoked by daily smokers . The intervention was more successful among girls than boys The article presents 2-year follow-up data from a school-based tobacco use prevention project design ed to test the effectiveness of 3 primary components in social influence programs . The components either teach refusal skills , awareness of social value misperceptions , or physical consequences . Curricula were tested with a r and omized experiment involving 48 junior high schools . These data suggested that ( a ) a physical-consequences curriculum is successful at attenuating increases in adolescent smokeless tobacco use , ( b ) cigarette experimentation may be attenuated by various approaches , and ( c ) a comprehensive program with all 3 components was necessary to attenuate increases in weekly use of both forms of tobacco . These results also indicate that school-based tobacco use interventions can be effective at least 2 years postprogram , after students make their transition to high school Factors associated with changes in the smoking behaviour of approximately 6000 schoolchildren ( two cohorts aged between 10 and 12 years in 1979 ) over 12 months are described . They were measured twice as part of a r and omized controlled trial of a smoking prevention programme . Four groups were defined : ( a ) those who became smokers ( adopters ) ; ( b ) those who remained non-smokers ; ( c ) those who became non-smokers ( quitters ) , and , ( d ) those who remained smokers . Personal and social variables were ordered using a logistic regression model according to the strength of their association with adopting and quitting smoking . Factors distinguishing adopters from children who remained nonsmokers were , being a member of the older cohort , having friends who smoke , having siblings who smoke , approving of cigarette advertising and having a relatively large amount of money to spend each week . Factors distinguishing quitters from children who continued to smoke were , having siblings who do not smoke , being a member of the younger cohort , disapproving of cigarette advertising and having a relatively small amount of money to spend each week . Initial attitude scores were indicative of future smoking behaviour and where smoking behaviour changed , attitudes also changed so that the two remained congruent . The younger cohort improved their knowledge of smoking hazards over the year irrespective of their smoking behaviour . The older cohort showed significant differences in knowledge which were dependent upon smoking category , with 1980 smokers having lower knowledge scores than non-smokers and showing an apparent decrement in their previous knowledge The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students ( n = 1,311 ) from 10 suburban New York junior high schools . The prevention strategy attempted to reduce intrapersonal pressure to smoke , drink excessively , or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances . Additionally , this study was design ed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers . Results indicated that the prevention program had a significant impact on cigarette smoking , excessive drinking , and marijuana use when implemented by peer leaders . Furthermore , significant changes were also evident with respect to selected cognitive , attitudinal , and personality predisposing variables in a direction consistent with non-substance use . These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse This study reports outcome evaluation results from a segment of one of the most widely used drug education/prevention programs entitled “ Here 's Looking At You 2000 . ” HLAY 2000 was offered to the seventh and eighth grade students ( n = 463 ) by regular classroom teachers of Yadkin County Schools located in one of the rural areas in North Carolina . Six schools served as the experimental group while two r and omly selected schools served as a control group . The program was implemented during the 1990–91 school year This study evaluated the effects of a school-based intervention on growth trajectories of smoking , drinking , and antisocial behavior among early adolescents . Seven middle schools were r and omized to intervention or comparison conditions and students in two successive cohorts ( n = 1484 ) provided five waves of data from sixth to ninth grade . The Going Places Program , included classroom curricula , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects , including reducing increases in friends who smoke , outcome expectations for smoking , and smoking progression , but had non-significant effects on drinking or antisocial behavior . The Going Places Program was effective in preventing increases in smoking progression , but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed Recent studies have supported the efficacy of approaches to smoking prevention that focus primary attention on social and psychological factors implicated in initiation of adolescent cigarette smoking . This article reports first year data from a large-scale smoking prevention study conducted within three geographic regions of New York State . The sample consists of 5,954 seventh grade rs from 56 middle/junior high schools . Schools were r and omly assigned to ( 1 ) receive the Life Skills Training ( LST ) prevention program with a one-day teacher training workshop ; ( 2 ) receive the LST prevention program with teacher training provided by video tape ; or ( 3 ) serve as a comparison group . This study was design ed to further test the efficacy of this type of smoking prevention program and to compare the relative effectiveness of two different types of provider training in an effort to learn more about the potential effectiveness of this prevention strategy when implemented under " real world " conditions . Pretest and postt This paper describes the third and final evaluation of drug education conducted by the Napa Project . In the present course students were taught decision-making skills , personal goal setting , a motivational model , peer and media influences on behavior , assertiveness training , and information on the consequences of , and alternatives to , alcohol , cigarette , and marijuana use . The evaluation employed an experimental design in which seventh grade classes in two schools were matched and then r and omly assigned to experimental and control conditions . Pre- , post- , and follow-up tests covered drug knowledge ; drug attitudes ; perceived benefits and costs of substance use ; perceived peer attitudes toward , and use of , substances ; and intentions to use , current use and lifetime use of various substances . The posttest and follow-up data were analyzed using hierarchical analyses of covariance controlling for corresponding pretest scores . The course was found to have had no significant effect on girls and only a few effects at follow-up for boys BACKGROUND Knowledge about age of smoking initiation among adolescents in China is helpful for exploring cultural differences in adolescent smoking behavior and informative for global tobacco control . However , little has been documented on this issue . METHOD Adolescents ( 6,473 ) attending grade s 7 , 8 , and 9 completed the baseline survey of a longitudinal , r and omized smoking prevention trial . Data were collected in classrooms with a paper- and -pencil question naire . A survival model was used in the statistical analysis . RESULTS The hazard of smoking initiation for boys showed a pattern previously observed in the United States : very low ( < 2 % ) before 7 years of age , increasing rapidly after age 10 , and peaking at 14 - 15 years of age . The hazard for girls was below or around 1 % until 12 years of age before it increased . The hazard levels were similar for adolescents both in urban and in rural areas , but higher for those in grade 7 than in grade s 8 and 9 . CONCLUSIONS Chinese boys in Wuhan , China , experienced a hazard pattern of smoking initiation by age similar to those observed in the United States , while Chinese girls there experienced a rather low risk of smoking initiation . The hazard pattern suggests that the best time for smoking prevention is between 10 and 15 years of age . Adolescents in lower grade s are at higher risk of early smoking initiation , suggesting a potential cohort effect in adolescent smoking initiation in Wuhan , China For students to realize the benefits of behavior change curricula for disease prevention , programs must be implemented effectively . However , implementation failure is a common problem documented in the literature . In this article , teacher training is conceptualized as a behavior change process with explicit teacher motivation components included to help effect the intended behavior ( i.e. , implementation ) . Using this method , the Hutchinson Smoking Prevention Project , a r and omized controlled trial in school-based smoking prevention , conducted 65 in-service programs , training nearly 500 teachers ( Grade s 3 - 10 ) from 72 schools . Implementation was monitored by teacher self-report and classroom observations by project staff . The results were favorable . All eligible teachers received training , virtually all trained teachers implemented the research curriculum , and 89 % of observed lessons worked as intended . It is concluded that teacher training conceptualized as a behavior change process and including explicit teacher motivation components can promote effective implementation of behavior change curricula in public school classrooms We describe the results of a r and omized controlled study on the efficacy of a smoking prevention program based on behavioral methods ( Waterloo Smoking Prevention Program 1 , adapted ) . 792 children of 12 - 13 years of age from the Health District of Rozzano ( MI ) were the study base . The program was delivered directly by voluntary teachers during school classes . Two follow-up , at 18 and 36 month from the end of the program were conducted using self-administered question naire and telephonic interviews . At 36 months the proportion of non-smokers was higher in the intervention group ( 55 % vs 44 % ; OR ( adjusted for clustering ) = 1.7 ; p = .03 ) and that of regular ( at least one cigarette a week ) smokers lower ( 22 % vs 39 % ) than in the control group . We found no difference of effect between males and females students . Social pressure associated with starting to smoke ( friends , sibsters , parents smokers ) measured before intervention had no demonstrable influence on efficacy . We propose this kind of intervention for Italian students as an effective and low-cost program , even though more research is needed to maintain effectiveness of these kind of programs beyond adolescence The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is an elementary school cardiovascular health education field trial in progress in San Diego , California , New Orleans , Louisiana , Minneapolis , Minnesota , and Austin , Texas . Because a significant part of a child 's health behaviors are shaped within the home , CATCH is evaluating whether the effects of the school-based program are enhanced by the inclusion of a home-based program . A 7 x 7 x 10 r and omized design with 7 school-only and 7 school-plus-family intervention schools , along with 10 control schools is implemented at each site . The CATCH family intervention is implemented during Grade s 3 through 5 and consists of home-based curricula and Family Fun Nights focusing on healthier eating and increased physical activity during Grade s 3 and 4 , along with a smoking prevention curriculum in Grade 5 . CATCH is examining the effectiveness of family ( household ) involvement through changes in students ' dietary intake of fat and sodium . This paper describes the process evaluation methods used to document the extent of participation in the family program . Data reported for the third- grade Family Fun Nights held in the 28 family schools across all sites reflected an average student participation rate of 67 % . The average family member to student ratio was approximately 2:1 . Participation by all third- grade teachers and the majority of physical education specialists was observed Health promotion interventions can not work if people do not engage with them . The aim of this study was to examine whether disengagement from an adolescent smoking prevention and cessation intervention was an independent risk factor for regular smoking 1 and 2 years later . The data were taken from a cluster r and omised controlled trial , in the West Midl and s , UK , based on the transtheoretical or stages of change model . In this trial , 8,352 13 - 14-year old school pupils enrolled , and the data in this report were based on the 7,413 and 6,782 pupils present at 1 and 2 years follow-ups , respectively . The intervention group undertook three sessions using an interactive computer programme . At the end of the programme , pupils recorded their responses to it . Pupils were classed as engaged if they thought the intervention was both useful and interesting ; all others were classed as disengaged . R and om effects logistic regression related the number of times engaged to regular smoking at 1 and 2 years follow-up , adjusted for school absences and 11 potential confounders . The majority of pupils were engaged by the intervention . For participants using the intervention three times but not engaging once , the odds ratios ( 95 % confidence intervals ) for smoking at 1 and 2 years relative to the controls were 1.83 ( 1.41 - 2.39 ) and 1.70 ( 1.38 - 2.11 ) . For those engaging three times , they were 0.79 ( 0.60 - 1.03 ) and 0.96 ( 0.75 - 1.21 ) . There was no interaction with baseline intention to smoke , classified by stage of change , but there was a borderline significant interaction with baseline smoking status , with disengagement acting as a stronger risk factor among baseline never-smokers . We conclude that disengagement from interventions is a risk factor for smoking independently of experimentation with cigarettes . The best explanation is that disengagement from school , an established risk factor for smoking , generalises to disengagement from didactic school-based health promotion programmes The longitudinal study compared effects of varying amounts of tobacco instruction ( one , two , and three years ) on the knowledge , attitudes , and behavioral intentions of urban elementary students . A three-year , fourth-through-sixth grade tobacco prevention curriculum was developed based on the Centers for Disease Control and Prevention 's Guidelines for School Health Programs to Prevent Tobacco Use and Addiction . The curriculum comprised five , 45-minute lessons per year . The same trained instructor taught the curriculum all three years . Six intervention schools were taught the curriculum , and two control schools were not . A 49-item question naire was used to assess tobacco knowledge , attitudes , and behavioral intentions . The experimental group 's posttest knowledge and attitude scores were significantly higher than the control group 's posttest scores . No significant differences occurred in posttest behavioral intention scores between the control and intervention groups This analysis examined the possible synergistic effect of exposure to the National Youth Anti-Drug Media Campaign and a classroom-based drug prevention curriculum among 9th grade students participating in a r and omized trial of ALERT Plus . A total of 45 South Dakota high schools and their middle-school feeder(s ) were r and omly assigned to an ALERT condition ( basic prevention curriculum delivered in 7th and 8th grade s ) , an ALERT Plus condition ( basic curriculum with booster lessons added for 9th and 10th grade s ) , or a control condition . Marijuana use in the past month was significantly less likely among ALERT Plus students reporting at least weekly exposure to anti-drug media messages . The National Youth Anti-Drug Media Campaign may have led to reductions in marijuana use among youth who simultaneously received school-based drug prevention BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the st and ardized protocol and Manuals of Operation , a steering committee for study governance , a distributed data system , an extensive quality control system , and a Data and Safety Monitoring Board . METHOD CATCH tested the effectiveness of changes in school lunches , physical education , smoking policy , curricula , and family activities . Ninety-six elementary schools in four states were r and omized to intervention or control conditions . The baseline cohort comprised 5 , 106 ethnically diverse third grade rs followed through fifth grade . RESULTS The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls . Significant increases in moderate to vigorous activity levels in existing physical education classes were made as well . Changes in self-reported dietary , physical activity , and psychosocial measures were significant . There were no significant differences in the physiological measures . Measurement error was generally low for all physiologic measures except skinfolds , indicating a high level of reliability . Across all sites , the coefficients of variation for lipids , height , and weight were less than 3 % , whereas for skinfolds , they were considerably higher , ranging from 6 to 8 % . Intraclass correlations for lipid studies were also uniformly high at 0.99 . Interobserver agreement scores for SOFIT were greater than 90 % for 9 of the 11 activities observed . Data entry error rates were low with less than five errors per 1,000 fields for all forms . CONCLUSIONS The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion . Many of the strategies used in this complex multicenter trial in the areas of design and analysis , measurement , training , data management , and quality control protocol s might be appropriate for adoption in other studies This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication BACKGROUND Adolescents at risk for cigarette smoking are difficult to reach with conventional interventions but have substantial exposure to the mass media . This study is the first to show that smoking prevention messages presented through the mass media can have large and durable effects on higher risk adolescents . METHODS Students in two communities received media and school interventions beginning in grade s 5 - 7 ; those in matched comparison communities received school interventions . Media interventions were targeted to higher risk youths . School surveys were conducted before and after the interventions , in grade s 4 - 6 and grade s 8 - 10 . Two years after interventions ended , when participants were in grade s 10 - 12 , school and telephone surveys were conducted to assess smoking status . Survey participants ( n = 2,860 ) were classified at baseline as having higher or lower risk for becoming a smoker . RESULTS Smoking prevalence within the higher risk sample was significantly lower for those receiving media-school interventions than for those receiving school interventions only ( odds ratio = 0.71 ) . Effects on the lower risk sample were similar in magnitude but marginally significant . CONCLUSIONS Mass media and school interventions achieved lower smoking rates among higher risk youngsters 2 years following completion of the interventions . This strategy represents a uniquely effective method for communicating with a high-priority group A six-year , school-based prevention program , which modified classroom teacher practice s , offered parent training , and provided child social skills training , was evaluated for its effects on school failure , drug abuse , and delinquency among low-income urban children . Compared to a low-income control group , children in the intervention group showed enhanced school commitment and class participation . The girls in the group also evidence d lower rates of substance use initiation , while the boys exhibited increased social and school work skills The study examined the effectiveness of a psycho-social tobacco use prevention intervention with a refusal skills training component on the refusal skills of high-risk adolescents , and investigated skill acquisition as related to subject demographics , performance of health facilitators and attendance at skills training sessions . Tobacco refusal skills were assessed for a group ( n = 389 ) of high-risk , seventh- grade students participating as intervention and control subjects in Project SHOUT , a large tobacco use prevention program in the San Diego area . In addition , subject demographics , ratings of health facilitator performance and information about subjects ' attendance at skills training sessions were collected . Subjects ' responses to audiotaped peer offers of cigarettes and smokeless tobacco were coded for content and quality . Greater tobacco refusal skills among intervention subjects was hypothesized . Further health facilitator performance , attendance at training sessions and subject demographics were thought to be related to skill acquisition . High-risk intervention subjects gave significantly higher quality tobacco-refusal responses than did controls , although the differences between means were small . Results suggested that Hispanic adolescents were particularly receptive to the refusal skills training . The association between health facilitator performance and skill acquisition varied by subject ethnicity , as did the relationship between attendance at training sessions and skill acquisition Project Northl and is a community-wide research program funded by the National Institute on Alcoholism and Alcohol Abuse , for a 5-year period ( 1990 - 95 ) . The aim of the study is to prevent or delay onset of alcohol use among young adolescents , as well as to reduce use among those who are already drinkers . Twenty communities were recruited in northeastern Minnesota , an area referred to as the Northl and , Arrowhead or Iron Range region , and then were r and omly assigned to either Education or Delayed Program conditions . The 10 Education school districts have agreed to participate in 3 years of intervention programs in schools , with parents and in the community-at-large . One group of young adolescents , the Class of 1998 ( sixth grade students in the 1991 - 92 school year ) , form the study cohort . Surveys ( 1991 - 94 ) of the Class of 1998 , their parents , community leaders and alcohol merchants are the primary components of the program 's evaluation . Many conceptual and method ological questions emerged during the development of the research protocol s for Project Northl and over the past 2 years . These questions are the impetus for this article . Specifically , the focus on young adolescents and alcohol use was selected , as contrasted with older adolescents or with multiple problem behaviors . The project was design ed using a community-wide model that addresses both supply and dem and issues , rather than limited to a school-based model . Intervention strategies and evaluation methods were chosen that could address community-level as well as individual-level behavior change , which required the development and application of new technologies . The rationale for these decisions may be useful to others considering community-wide health promotion efforts Abstract Objectives : To examine whether a year long programme based on the transtheoretical model of behaviour change , incorporating three sessions using an expert system computer program and three class lessons , could reduce the prevalence of teenage smoking . Design : Cluster r and omised trial comparing the intervention to a control group exposed only to health education as part of the English national curriculum . Setting : 52 schools in the West Midl and s region . Participants : 8352 students in year 9 ( age 13 - 14 years ) at those schools . Main outcome measures : Prevalence of teenage smoking 12 months after the start of the intervention . Results : Of the 8352 students recruited , 7444 ( 89.1 % ) were followed up at 12 months . The intention to treat odds ratio for smoking in the intervention group relative to control was 1.08 ( 95 % confidence interval 0.89 to 1.33 ) . Sensitivity analysis for loss to follow up and adjustment for potential confounders did not alter these findings . Conclusions : The smoking prevention and cessation intervention based on the transtheoretical model , as delivered in this trial , is ineffective in schoolchildren aged 13 - 14 . Key messages The transtheoretical model proposes that individuals move through a series of stages in behaviour change A computer programme gave 13 and 14 year old school students tailored information about what stage they were in and what to do to move to the next stage Students given this information were no more likely to move stage , refrain from smoking , or stop smoking than those exposed to ordinary classroom health education There is no evidence that the computerised expert system based on the transtheoretical model is effective in smoking prevention and Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls OBJECTIVES Project Northl and is an efficacy trial with the goal of preventing or reducing alcohol use among young adolescents by using a multilevel , communitywide approach . METHODS Conducted in 24 school districts and adjacent communities in northeastern Minnesota since 1991 , the intervention targets the class of 1998 ( sixth- grade students in 1991 ) and has been implemented for 3 school years ( 1991 to 1994 ) . The intervention consists of social-behavioral curricula in schools , peer leadership , parental involvement/education , and communitywide task force activities . Annual surveys of the class of 1998 measure alcohol use , tobacco use , and psychosocial factors . RESULTS At the end of 3 years , students in the intervention school districts report less onset and prevalence of alcohol use than students in the reference districts . The differences were particularly notable among those who were nonusers at baseline . CONCLUSIONS The results of Project Northl and suggest that multilevel , targeted prevention programs for young adolescents are effective in reducing alcohol use Little documentation exists regarding the functioning of formalized adolescent groups as drug abuse prevention agents . Two studies are described that were conducted at high schools whose students are at high risk for drug abuse . Twenty-one schools were r and omly assigned to one of three conditions : ( a ) st and ard care , ( b ) classroom drug abuse education only , or ( c ) classroom plus school-as-conununity . Results of the first study tndicated that the school-as-communtty component — which involved weekly meetings and periodic events at seven schools — was imple mented as planned , drug abused focused , and perceived as productive in discouraging drug abuse . In the second study , staff in the classroom plus school-as-community condition self- reported involvement in the greatest number of community activities across the school year , compared with staff from the other two conditions . These two studies support the feasibility of formalized groups of high-risk youth to promote drug-free events The purpose of this project was to develop and test culturally appropriate , low literacy , smoking cessation intervention material s design ed to increase quit rates and prevent relapse postpartum for low-income African American and Hispanic women . A quasi-experimental , pretest-posttest design was used . Four Women , Infants , and Children ( WIC ) clinic sites in south and central Los Angeles were identified , pair-matched based on ethnic mix , and r and omized to intervention ( 2 sites ) or control status ( 2 sites ) . Participants were 18 years of age or older and either current or exsmokers ( stopped smoking in the past year ) . The intervention group received the " Time for a Change : A Program for Healthy Moms and Babies " program including a 15-minute one-to-one counseling session and self-help guide , incorporating behavior-change strategies , booster postcard , and incentive contest . All material s were design ed to match the cultural , language , and literacy needs of the target population . The smoking cessation intervention had a positive impact on both quit-smoking behavior during pregnancy and relapse prevention postpartum . Almost twice as many smokers in the intervention group ( 43 % ) reported quitting smoking at 9 months , compared to the control group ( 25 % ) ( P < 0.01 ) . At 6 weeks postpartum , 25 % of the intervention baseline smokers were abstinent , compared to 12 % of the control group ( P < 0.01 ) . Although no significant differences were observed for relapse during pregnancy among exsmokers at 6 weeks postpartum , a significantly higher proportion of intervention exsmokers were still abstinent ( 79 % ) , compared to control exsmokers ( 62 % ) ( P < 0.01 ) . For the exsmokers , relapse prevention rates remained significant when adjusted for cotinine vali date d abstinence . ( ABSTRACT TRUNCATED AT 250 WORDS Students ( N = 4,466 ) attending 56 schools in New York State were involved in a 3-year study testing the effectiveness of a cognitive-behavioral approach to substance abuse prevention . In a r and omized block design , schools were assigned to receive ( a ) the prevention program with formal provider training and implementation feedback , ( b ) the prevention program with videotaped provider training and no feedback , or ( c ) no treatment . After pretest equivalence and comparability of conditions with respect to attrition were established , students who received at least 60 % of the prevention program ( N = 3,684 ) were included in analyses of program effectiveness . Significant prevention effects were found for cigarette smoking , marijuana use , and immoderate alcohol use . Prevention effects were also found for normative expectations and knowledge concerning substance use , interpersonal skills , and communication skills OBJECTIVES Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents , few have assessed the long-term effects of such programs . Such information is essential for judging how long prevention benefits last . This paper reports results over a 6-year period for a multisite r and omized trial that achieved reductions in drug use during the junior high school years . METHODS The 11-lesson curriculum , which was tested in 30 schools in eight highly diverse West Coast communities , focused on helping 7th and 8th grade students develop the motivation and skills to resist drugs . Schools were r and omly assigned to treatment and control conditions . About 4000 students were assessed in grade 7 and six times thereafter through grade 12 . Program effects were adjusted for pretest covariates and school effects . RESULTS Once the lessons stopped , the program 's effects on drug use stopped . Effects on cognitive risk factors persisted for a longer time ( many through grade 10 ) , but were not sufficient to produce corresponding reductions in use . CONCLUSIONS It is unlikely that early prevention gains can be maintained without additional prevention efforts during high school . Future research is needed to develop and test such efforts BACKGROUND This study reports the prevalence of adolescent smoking in the urban and rural areas of Wuhan , China , the capital of Hubei Province , on the Yangtze River in central China . METHODS Smoking behavior was examined by age , gender , and urbanicity as part of the Wuhan Smoking Prevention Trial . Subjects included 6994 seventh- to ninth- grade students attending 22 r and omly selected schools in urban and rural districts . Outcome measures included lifetime smoking , past-30-day smoking , established smoking ( > 100 cigarettes in lifetime ) , and susceptibility to smoking ( absence of a firm commitment not to smoke ) . RESULTS Lifetime smoking prevalence was 47 % among boys and 18 % among girls . Past-30-day smoking prevalence was 16 % among boys and 4 % among girls . Established smoking prevalence was 2 % among boys and 0 % among girls . The prevalence of susceptibility to smoking was 31 % among boys and 10 % among girls . Smoking increased significantly with age ( p<.0005 ) . Susceptibility was more prevalent in rural areas than in urban areas ( p<.05 ) , but there were no urban-rural differences in lifetime , past 30-day smoking , or established smoking . Trend analyses revealed that smoking increased with age more rapidly among boys than among girls ( p<.05 ) . Smoking was more prevalent among rural boys than among urban boys , but it was more prevalent among urban girls than among rural girls ( p<.05 ) . CONCLUSIONS Adolescent smoking is a significant public health problem in China . Boys are at particularly high risk , as are girls living in urban areas . Effective smoking prevention programs for adolescents , as well as restrictions on tobacco industry marketing and youth access to tobacco , are needed to prevent tobacco-related morbidity and mortality in China UNLABELLED BACKGROUND . There are strong theoretical reasons for including a family component with a school-based intervention aim ed at eating , activity , and smoking behaviors , but the empirical findings to date are limited and show mixed results . The overall CATCH family intervention added only knowledge and attitudinal effects , but no additional behavioral outcomes . This study provides a dose analysis of the family component of the CATCH study by assessing the effect of the level of adult participation . METHOD This secondary analysis included students who attended a CATCH family intervention school during all 3 years of the study . The extent of the adult-child interaction , the key aspect of the CATCH family intervention , was measured by the number of activity packets that an adult household member completed with the child . Multiple regression analysis was used to assess the association of adult participation with the child 's knowledge , attitudes , and behaviors related to diet and physical activity . RESULTS Statistically significant results suggested that dose effects were found for knowledge and attitudes related to diet and physical activity . These effects were more pronounced for minority and male students . CONCLUSIONS These results suggest that dose response of a family intervention has been shown in the acquisition of positive knowledge and attitudes toward health habit changes . The methodology of dose response can be applied to other health promotion projects INTRODUCTION This paper describes the experimental design and baseline characteristics of the Hutchinson Smoking Prevention Project ( HSPP ) , a 15-year trial to determine to what extent a grade 3 - 12 school-based tobacco use prevention intervention can deter tobacco use throughout and beyond high school . DESIGN Trial design features include use of the school district as the unit of r and omization , inclusion of the school district 's entire enrollment of 3rd grade rs , long-term follow-up of the entire original cohort , and sample size and evaluation methods that account for the group-r and omization and intraclass correlation of endpoints within school districts . The theory-based intervention is teacher-led and includes grade 3 - 10 curriculum units , teacher training , grade 9 - 12 tobacco use cessation material s , and high school staff newsletters . RESULTS Baseline data were collected on the trial cohort of 8388 children and their parents and on the 40 collaborating school districts and communities . A comparison of the distribution of baseline variables between experimental conditions shows good balance . CONCLUSIONS . The HSPP trial 's experimental design will provide a rigorous test of the intervention . The balance in baseline variables between the experimental and control conditions will help provide assurance that the trial 's intervention effectiveness results , scheduled for publication in 2000 , will be unbiased BACKGROUND This paper examines whether the Massachusetts Tobacco Control Program is affecting the rates of smoking and smokeless tobacco use among Massachusetts ' youth . METHODS School survey data from the Massachusetts Prevalence Study were analyzed to estimate differences between 1993 and 1996 rates of youth cigarette and smokeless tobacco use , attitudes toward smoking , and awareness of cigarette ads and promotions of antismoking messages . RESULTS Lifetime and Current Smoking rates declined significantly among middle school males , contrasting with stable national trends . Among girls in this age group , Lifetime and Current Smoking did not change significantly . Hispanic middle school students exhibited a significant decline in Lifetime Use . There were no significant changes in Lifetime or Current Smoking rates among high school students . Lifetime use of smokeless tobacco declined among middle school students while Current Use declined among both middle and high school students . Students reported declines in awareness of cigarette ads or promotions and increases in awareness of antismoking messages . CONCLUSIONS These results provide evidence for cautious optimism regarding the impact of tobacco control , but indicate that these efforts should begin earlier and that additional research is needed to underst and and address the problems of tobacco use by girls OBJECTIVE To reduce tobacco use among adolescents . METHODS Thirty schools in New Delhi , India , were r and omly assigned to 3 conditions : school-based and family-based intervention , school-based intervention only , or control group . Students were in the seventh grade at pretest ( N = 4,776 ) . The smoking intervention included posters , booklets , classroom activities , debates , and a signature campaign . The family intervention involved home activities . The survey measured tobacco knowledge , attitudes , offers , use , and intentions . RESULTS Intervention students were significantly less likely than controls to have been offered , received , experimented with , or have intentions to use tobacco . CONCLUSION The project had a significant impact on tobacco use PURPOSE To determine whether self-concept , gender , and age are significant factors in an adolescent 's transition through stages of smoking to regular smoking . METHODS A question naire composed of 29 items ( nine questions pertaining to smoking behavior and 20 to four self-concept variables : physical , family , social , and peer self-concept ) was administered to 368 r and omly selected high school adolescents ( 188 males and 180 females ) aged 12 - 17 years during regular contact ( roll call ) time . RESULTS Overall , 40.5 % of the sample had tried tobacco ( excluding chewing tobacco ) ( 42.8 % of females and 38.3 % of males ) . Although prevalence of smoking varied according to the stage of smoking , it increased with age . With reference to self-concept , Scheffe post hoc contrasts revealed a statistically significant difference between physical self-concept and the remaining measures of self-concept ( peer , family , and social ) and at each stage of smoking . The effect for male students was less than for females . CONCLUSION Programs aim ed at prevention and intervention should incorporate strategies which are commensurate with female lifestyles and the more positive aspects that individuals might experience on quitting Reaching nonvolunteer female smokers with effective smoking cessation programs is a critical public health challenge . Smokers ( N = 2,786 ) among 15,004 female members of a health maintenance organization who completed a routine needs assessment were invited into the " UCLA Preventive Health Behavior Study , " consisting of five telephone interviews over 2 years assessing health practice s. Participants ( N = 1,396 ) were r and omized into experimental or control conditions of an unsolicited , mailed , self-help smoking cessation program . Subjects were not alerted to the link between the program and the health study . Smoking status was assessed at 1 , 6 , 12 , and 18 months . Across all subjects , point prevalence at 18 months was 18.62 , and continuous abstinence was 2.71 % . No difference was found between treatment and control groups regarding smoking status or readiness to stop smoking -- raising questions about the value of mailing cessation material s to nonvolunteers . Quit rates increased over the 18-month follow-up ; those still smoking at 18 months reported increased readiness to quit . Predictors at each follow-up point were examined multivariately How effective are peer-led programmes in preventing the uptake of smoking by children ? In 1981 , we conducted a r and omized controlled trial of a school-based educational programme for the prevention of smoking in children who were in their seventh year at school . In this article , the reported results of two years of follow-up confirm an earlier report that both teacher-led and peer-led programmes result ed in a reduction , to about the same degree , in the uptake of smoking by girls , while only the teacher-led programme appeared to be effective in boys . In girls , both the teacher-led and peer-led programmes maintained their effects over the two years of follow-up with adjusted differences in prevalence rates of the uptake of smoking relative to the control group of -6.6 % ( 95 % CL , -17.3 % , 4.0 % ) and -8.1 % ( 95 % CL , -18.9 % , 2.7 % ) , respectively , after two years . In boys , the effect of the teacher-led programme was reduced substantially by the second year with a difference in the prevalence rate of -2.8 % ( 95 % CL , -11.2 % , 5.6 % ) ; for the peer-led programme the difference in the prevalence rate was + 6.4 % ( 95 % CL , -3.6 % , 16.4 % ) . Other variables which had a significant effect on the smoking behaviour were the perceived response to cigarette advertising , parental and sibling smoking status , the perceived parental sanctions on smoking behaviour , selected peer influences and the intention to smoke . The children 's perceived responses to cigarette advertising showed the strongest and most consistent evidence of an effect on the uptake of smoking by children who initially were non-smokers . After adjustment for the effects of other variables there was an excess of 15.0 % ( 95 % CL , 2.1 % , 27.9 % ) in the prevalence rate of smoking after two years for girls who thought that they were influenced by advertising compared with those who did not . The corresponding difference for boys was 15.3 % ( 95 % CL , 4.0 % , 26.6 % ) . As smoking-prevention programmes only may delay the onset of smoking in children , it is important that legislative measures be introduced to reduce the effects of cigarette advertising OBJECTIVE To test a classroom-based intervention to reduce cardiovascular disease risk factors in elementary school children . STUDY DESIGN This was a r and omized , controlled field trial in 12 schools across North Carolina , stratified by geographic region and urban/rural setting . Subjects were 1274 third and fourth grade rs ( 48 % boys ) . The intervention , taught by regular classroom and physical education teachers , provided all children an 8-week exercise program and 8 weeks of classes on nutrition and smoking . Data were analyzed at the school level with survey regression models and at the individual level with multivariate analysis of variance and analysis of covariance models ; 95 % confidence intervals were computed . RESULTS Children in the intervention group had significantly greater knowledge ( 7.9 % more correct ) and a significant increase in self-reported physical activity than children in the control group . Trends for the intervention group were a reduction in total cholesterol level ( -5.27 mg/dl ) , an increase in aerobic power , a reduction in body fat , and smaller rise in diastolic blood pressure than control children . CONCLUSIONS This classroom-based , public health approach improved children 's cardiovascular disease risk profiles ; it is practical and fairly easy to incorporate into the school day . All children directly receive the potential benefits of the intervention without a risk of labeling . This program can improve health knowledge , habits , and health outcomes of young children at a time when health habits are being formed Sixth- grade students ( N = 56 ) were assigned r and omly to one of four experimental conditions : pretest and primary prevention ; primary prevention ; pretest ; and neither pretest nor primary prevention . In eight group sessions , primary prevention students learned facts , problem solving , decision making , self-instructions and interpersonal skills to help keep them from using tobacco . All students completed posttests and a six-month follow-up . Compared with untrained controls , trained students had greater knowledge of smoking , more perspectives on tobacco problems , better linkages between problems and solutions , more insights on the consequences of nonsmoking decisions and greater nonverbal and verbal competence in tobacco use situations . Follow-up data showed trained students with stronger commitments to tobacco abstinence , more frequent refusals of tobacco , and less smoking than controls . Midway through seventh grade , 8 % of trained students and 37.5 % of controls had smoked in the most recent month OBJECTIVES This study examined whether interventions aim ed at aggressive/disruptive classroom behavior and poor academic achievement would reduce the incidence of initiation of smoking . METHODS An epidemiologically based , universal r and omized preventive trial involved 2311 children in 2 classroom-based preventive interventions or controls . Each intervention was directed at 1 of the aforementioned 2 antecedents over first and second grade s in 19 urban schools . RESULTS Smoking initiation was reduced in both cohorts for boys assigned to the behavioral intervention . CONCLUSIONS Targeting early risk antecedents such as aggressive behavior appears to be an important smoking prevention strategy A one year r and omized controlled trial was used to evaluate the effectiveness of a smoking prevention programme design ed by health educationalists for 10 - 12 year old primary schoolchildren . The study was carried out in the Hunter Region of New South Wales , Australia , using a sample of over 6000 children which would be large enough to detect , with high probability , differences of about 5 % in smoking prevalence between the treatment and control groups . We report the results from the children surveyed in 1979 and 1980 , before and after the programme was implemented . It was found that there were no significant differences in smoking behaviour between treatment and control groups . The changes that the programme did bring about were very small compared with the overall increases in smoking prevalence which occurred during the study period . The programme 's effectiveness varied with both the age and sex of the children . It was most successful among older girls , aged 11 - 12 years , for whom smoking prevalence rates increased from 10.7 % in 1979 to 22.6 % in 1980 in the treatment group compared with 6.2 % to 26.8 % in the control group . It was least successful for younger boys , aged 10 - 11 years , for whom smoking increased from 9.4 % to 14.5 % in the treatment group compared with 10.3 % to 11.8 % in the control group . Attitudes changed in parallel with changes in smoking behaviour . Changes in knowledge differed only slightly between treatment and control groups . Inadequate implementation of the programme by some teachers may have been associated with adverse effects on the children 's behaviour , attitudes and knowledge A cognitive-developmental model postulates three predominant adolescent dispositions ( self-definition , social compliance , and affect regulation ) which may impede or facilitate transitions in stages of smoking . The purpose of the present prospect i ve study was to build on the findings supporting this model . One hundred schools were r and omly assigned to either receive or not receive a social influences smoking prevention program . A baseline survey , including smoking behavior and dispositional items , was administered in the sixth grade in 1990 , interventions were delivered in the sixth and seventh grade s , and a survey was administered following the seventh grade intervention . Principal component patterns , based on dispositional items , were very similar for grade s 6 and 7 , did not vary by gender , and the components ( rebelliousness , rejection of adult authority , personal dissatisfaction , and peer approval ) were correlated . All smoking-stage transitions were positively related to rebelliousness for boys . The relationship of the dispositional scores with smoking-stage transitions was more complex for girls . Receiving the program modified the effects of the dispositional risk scores , particularly for girls The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multicenter trial design ed to test the effectiveness of school and family-based cardiovascular health promotion for preadolescents . CATCH interventions target multiple cardiovascular health behaviors such as dietary intake of fat and sodium , physical activity , and tobacco use . Evaluation includes physiological , psychosocial , behavioral , and process measures . An important aspect of the process evaluation is the assessment of environmental factors and " secular events " in both intervention and control schools that may affect outcomes independently of the CATCH interventions . With such information , CATCH investigators are able to isolate the impact of the CATCH intervention from competing ( non-CATCH ) factors as well as " track " proximal ( i.e. , immediate and short term ) changes related to the intervention that may in turn lead to " distal " ( long-term ) behavior change . The School Health Question naire , the major process evaluation tool for monitoring secular and environmental changes in the schools , is described in detail , and data describing tobacco-related environmental factors and secular events are presented The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects . Seven middle schools were r and omized to intervention or comparison conditions and students ( n = 1,320 ) in two successive cohorts provided five waves of data from sixth through eighth grade . The Going Places Program included classroom curriculum , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies , friends who smoke , and smoking . Friends who smoke mediated the program effect on adolescents ’ smoking progression . The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke BACKGROUND Two strategies for preventing the onset of alcohol abuse , and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties , California . The first strategy taught skills to refuse substance use offers . The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use . METHODS Four experimental conditions were created by r and omly assigning schools to receive ( a ) neither of the experimental curricula ( placebo comparison ) , ( b ) resistance skill training alone , ( c ) normative education alone , or ( d ) both resistance skill training and normative education . Students were pretested prior to the program and post-tested 1 year following delivery of the program . RESULTS There were main effects of normative education for summary measures of alcohol ( P = 0.0011 ) , marijuana ( P = 0.0096 ) , and cigarette smoking ( P = 0.0311 ) . All individual dichotomous measures of alcohol , marijuana , and tobacco use indicated significant reductions in onset attributable to normative education . There were no significant main effects of resistance skill training . CONCLUSION These results suggest that establishing conservative norms is an effective strategy for preventing substance use OBJECTIVE To develop a new measure of smoking initiation and progression among adolescents . METHOD This study used data from 2504 regular and alternative high school students to evaluate the psychometric properties of a new 3-item , 5-stage measure of smoking initiation and progression . RESULTS The categorization method showed good 4-week test-retest reliability ( .83 among boys and .87 among girls ) . The demographic distribution of adolescents into stages was consistent with previous research . CONCLUSION This 5-stage classification method could be a useful framework for describing variation along the smoking up-take and progression continuum The effectiveness of a fifteen session psychosocial smoking prevention strategy was tested on 902 seventh grade rs from seven junior high schools in suburban New York over 2 years . The prevention program was implemented by regular classroom teachers and consisted of a cognitive component dealing with the immediate consequences of cigarette smoking , a decision-making component , a relaxation-training component , a social skills training component , and a self-improvement component . In addition to testing the overall effectiveness of this approach , the relative efficacy of two different scheduling formats was compared and the extent to which “ booster ” sessions conducted during the year after completion of the program helped to maintain reductions in new smoking was also examined . Results indicated that the prevention program was able to reduce new cigarette smoking by 50 % at the end of the first year and by 55 % at the end of the second year for the intensive format condition . New regular cigarette smoking was reduced by 87 % in the second year for the students in the booster condition . Significant changes consistent with nonsmoking were also evident on several cognitive , attitudinal , and personality variables BACKGROUND An outcome evaluation of a high school tobacco control intervention using extracurricular activities developed by teachers and students is reported . METHODS Eligible subjects ( n = 3,028 ) had participated in a r and omized trial of an elementary school smoking prevention curriculum . Their high schools were matched in pairs ; one school in each pair was r and omly assigned to the intervention condition , the second to a " usual-care " control condition . Data were collected at the end of Grade s 9 and 10 . RESULTS For Grade 8 never smokers , regular smoking rates were significantly lower for males from intervention schools ( 9.8 vs 16.2 % , P = 0.02 ) at the end of Grade 10 . There were no significant differences among Grade 10 smoking rates for females , or for students of either gender with previous smoking experience in Grade 8 . CONCLUSIONS The extracurricular activities approach to tobacco control is practical to implement and has promise BACKGROUND This study evaluates the effects of a 3-year smoking prevention programme in secondary schools in Helsinki . The study is part of the European Smoking prevention Framework Approach ( ESFA ) , in which Denmark , Finl and , the Netherl and s , Portugal , Spain and the UK participated . METHODS A total of 27 secondary schools in Finl and participated in the programme ( n = 1821 ) . Schools were r and omised into experimental ( 13 ) and control groups ( 14 ) . The programme included 14 information lessons about smoking and refusal skills training . The 3-year smoking prevention programme was also integrated into the st and ard curriculum . The community-element of the programme included parents , parish confirmation camps and dentists . The schools in the experimental group received the prevention programme and the schools in the control group received the st and ard health education curriculum . RESULTS Among baseline never smokers ( 60.8 % ) , the programme had a significant effect on the onset of weekly smoking in the experimental group [ OR = 0.63 ( 0.45 - 0.90 ) P = 0.009 ] when compared with the control group . Being female , doing poorly at school , having parents and best friends who smoke and more pocket money to spend compared with others were associated with an increased likelihood of daily and weekly smoking onset . These predictors did not have an interaction effect with the experimental condition . CONCLUSION This study shows that a school- and community-based smoking prevention programme can prevent smoking onset among adolescents This paper describes the curricula contents , and presents data to evaluate the implementation , process and immediate post-test knowledge of Project Towards No Tobacco Use ( Project TNT ) . Four different school-based tobacco use prevention curricula were developed to counteract the effects of three types of tobacco use acquisition variables typically addressed within a comprehensive social influences program : ( 1 ) peer approval for using tobacco ( normative social influence ) , ( 2 ) incorrect social informational provided about tobacco use ( information social influence ) and ( 3 ) lack of knowledge or misperceptions about physical consequences result ing from tobacco use . Three curricula were design ed to counteract the effects of single acquisition variables , whereas a fourth curriculum was design ed to counteract the effects of combined social and physical consequences-related influences . These curricula were delivered to seventh grade students by trained project health educators to maximize implementation . ' Program ' schools , those schools that received one of these curricula , were compared to ' control ' schools that provided a systematic health education delivered by school personnel . A total of five conditions were contrasted through use of a r and omized experiment involving 48 southern California junior high schools . This paper documents high levels of implementation in all program conditions . Also , favorable process ratings were obtained across the four program conditions , using multiple measures and sources of ratings ( students , health educators and classroom teachers who observed curricula delivery ) . Finally , knowledge item sets completed by the students demonstrated discriminant validity across all five conditions . Because the program conditions were discriminable , yet were quite similar in implementation and process ratings , planned future study of behavioral outcomes can be interpreted as relatively uncontaminated by delivery or credibility confounds Thirty-four schools ( n=7426 consented sixth grade rs , 71 % of the eligible population ) were r and omized to conditions to test the hypothesis that Skills for Adolescence ( SFA ) , a widely used comprehensive life skills training curriculum with a dedicated drug education unit , is more effective than st and ard care in deterring and delaying substance use through middle school . Two-year posttest ( 1-year post-intervention ) data were collected from 5691 eighth grade rs ( 77 % of those who completed the sixth- grade survey and 87 % of those who completed the seventh- grade survey ) . Lifetime and recent ( last 30 days ) use of five substances or combinations of substances was compared using mixed-model regression to control for school clustering . There were two significant treatment main effects at the end of the eighth grade : lifetime ( P=.05 ) and recent ( P<.03 ) marijuana use were lower in SFA than control schools with pretest usage and salient demographic and psychosocial variables controlled . There was also one significant Treatment x Pretest Usage interaction around binge drinking . Baseline binge drinkers in SFA schools were less likely to report recent binge drinking than students in control schools ( P<.01 ) ; there were no treatment differences among baseline nonbinge drinkers . Analyses of potential mediators of SFA treatment effects on eighth- grade binge drinking and marijuana use suggested that SFA increased self-efficacy around drug refusal skills , but did not affect behavioral intentions , perceptions of harm , or perceived peer norms . These 2-year ( 1-year post-intervention ) outcomes offer some additional support for SFA effectiveness and the general thrust of school-based , life skills-based prevention programs . The promising sixth- through eighth- grade findings for SFA , a commercially available program , provide a further step in bridging a major gap in the " research to practice " literature : theory-based interventions that have documented behavioral effects have not enjoyed large-scale implementation , while intuition-based programs that have no documented effects still enjoy wide exposure OBJECTIVES We investigated the links between working for pay and adolescent tobacco use to determine whether working for pay increases smoking risk . METHODS We performed retrospective and prospect i ve analyses using data from a cohort of 799 predominantly African American students in Baltimore , Md , who had been followed since the first grade . RESULTS At the 10th year of follow-up , when the adolescents were aged 14 to 18 years , there was a positive relationship between the time they spent working for pay and current tobacco use . This relationship was attenuated somewhat after adjustment for potential selection effects . Adolescents who spent more than 10 hours per week working for pay also tended to initiate tobacco use earlier than did their peers . Among adolescents who had not yet used tobacco , those who started to work 1 year after assessment and those who worked over 2 consecutive assessment s had an elevated risk of initiating use relative to adolescents who did not start working . CONCLUSIONS There is a strong link between working for pay and adolescent tobacco use . Policymakers should monitor the conditions under which young people work to help minimize young workers ' tobacco use and potential for initiating use This study evaluated the effects of self-control skills intervention to prevent smoking with middle school subjects . Informed and consenting subjects were pretested , then by school were r and omly divided into three conditions : experimental , placebo , and test-only control . Experimental condition subjects received self-control skills intervention covering self-instruction , self-reinforcement , problem solving , and interpersonal communication . Placebo condition subjects received a discussion -oriented intervention employing health education methods to prevent smoking . Results at 15-month follow-up indicated that self-control and placebo condition subjects , relative to control condition subjects , improved more on measures of health knowledge and nonsmoking intentions . Self-control skills subjects had better 15-month follow-up scores than subjects in the other two conditions on measures of communication , self-instruction , self-praise , cigarette refusals , and noncompliance to smoke . Self-control condition subjects reported less weekly cigarette smoking compared with placebo and control condition subjects at final follow-up The Internet may be an effective medium for delivering smoking prevention to children . Consider This , an Internet-based program , was hypothesized to reduce expectations concerning smoking and smoking prevalence . Group-r and omized pretest-posttest controlled trials were conducted in Australia ( n = 2,077 ) and the United States ( n = 1,234 ) in schools containing Grade s 6 through 9 . Australian children using Consider This reported reduced 30-day smoking prevalence . This reduction was mediated by decreased subjective norms . The amount of program exposure was low in many classes , but program use displayed a dose-response relationship with reduced smoking prevalence . American children only reported lower expectations for smoking in the future . Intervening to prevent smoking is a challenge , and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation . Implementation remains the major challenge to delivering interventions via the Internet , both for health educators and research ers Data from a 2-year study describe tobacco use trends , perceptions , and prevention effects for 1,281 5th and 6th grade rs enrolled in 12 r and omly selected Washington State elementary schools . Youths were pretested , then r and omly divided by school into skills , discussion , and control groups . Preventive intervention curriculums for the skills and discussion groups included age-relevant information on smoked and smokeless tobacco use , peer testimonials , debates , games , and homework . Youths in the skills group also learned communication and problem-solving methods for h and ling difficult situations around tobacco use . Following intervention , youths were posttested , then retested semiannually for 2 years . During the 2-year study , three-quarters of all smokers and nonusers and half of all smokeless tobacco users maintained their statuses . Only 10 percent of all smokers and 3 percent of all smokeless users quit their habits . One in six reported new tobacco use , one-third of smokers began using smokeless tobacco , and two-thirds of all smokeless users began smoking during the study . Most youths at final measurement perceived smokeless tobacco as less of a health risk than smoking . Nearly one in two of all smokeless users intended to smoke , and two-thirds were actually smoking at 24-month followup . Both smoked and smokeless tobacco use rates increased in all groups , and youths in the skills intervention group consistently showed the lowest rates relative to the other groups . These findings demonstrate the potential of skills intervention methods for lowering tobacco use rates among adolescents OBJECTIVE Experimental evaluation of comprehensive community wide programme to prevent adolescent tobacco use . DESIGN Eight pairs of small Oregon communities ( population 1700 to 13 500 ) were r and omly assigned to receive a school based prevention programme or the school based programme plus a community programme . Effects were assessed through five annual surveys ( time 1–5 ) of seventh and ninth grade ( ages 12–15 years ) students . INTERVENTION The community programme included : ( a ) media advocacy , ( b ) youth anti-tobacco activities , ( c ) family communications about tobacco use , and ( d ) reduction of youth access to tobacco . MAIN OUTCOME MEASURE The prevalence of self reported smoking and smokeless tobacco use in the week before assessment . RESULTS The community programme had significant effects on the prevalence of weekly cigarette use at times 2 and 5 and the effect approached significance at time 4 . An effect on the slope of prevalence across time points was evident only when time 2 data points were eliminated from the analysis . The intervention affected the prevalence of smokeless tobacco among grade 9 boys at time 2 . There were also significant effects on the slope of alcohol use among ninth grade rs and the quadratic slope of marijuana for all students . CONCLUSION The results suggest that comprehensive community wide interventions can improve on the preventive effect of school based tobacco prevention programmes and that effective tobacco prevention may prevent other substance use OBJECTIVES This study determined the effect of provider ( nurse or teacher ) and training method ( workshop or self-preparation ) on outcomes of a social influences smoking prevention program . METHODS One hundred elementary schools were stratified by school risk score ( high risk = high smoking rate among senior students ) and assigned r and omly to conditions : ( 1 ) teacher/self-preparation , ( 2 ) teacher/workshop , ( 3 ) nurse/self-preparation , ( 4 ) nurse/workshop , and ( 5 ) control . Intervention occurred in grade s 6 to 8 . Smoking status at the end of grade 8 was the primary endpoint variable . RESULTS Intervention reduced grade 8 smoking rates in high-risk schools ( smoking rates of 26.9 % in control vs 16.0 % in intervention schools ) but not in low-risk schools . There were no significant differences in outcome as a function of training method and no significant differences in outcome between teacher-provided and nurse-provided interventions in high- and medium-risk schools . Although nurses achieved better outcomes than did teachers in low-risk schools , neither provider type achieved outcomes superior to the control condition in those schools . CONCLUSIONS Workshop training did not affect outcomes . Teachers and nurses were equally effective providers . Results suggest that programming should target high-risk schools OBJECTIVES This paper describes the 2-year follow-up of a 12-session version of an indicated drug abuse prevention program , Project Towards No Drug Abuse ( TND ) . Self-instruction programming often is used to help youth that are at high risk for dropout and drug abuse to complete their high school education . However , a health educator-led program is much more interactive . METHODS The effects of self-instruction versus health educator-led versions of this curriculum were examined . Eighteen schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , health educator-led classroom program , and self-instruction classroom program . Subjects were followed up 1 and 2 years later . Two-year results are reported here . RESULTS The self-instruction program produced no behavioral effects relative to the st and ard care control condition . The 2-year follow-up results indicated maintenance of program effects on cigarette smoking and hard drug use in the health educator-led version . CONCLUSIONS Project TND shows maintenance of effects on some drugs 2 years after program implementation , when most youth were young adults . More work is needed to learn how to maintain effects across substances . Continued exploration of modalities of implementation may be helpful Skills intervention to prevent cigarette smoking was evaluated with 689 adolescents . At 24-month follow-up , youths who received health information and skills intervention had lower intentions to smoke and less cigarette use than youths who received health information alone and youths who received no intervention . Conclusions about the effects of skills intervention are strengthened by the common preparation and r and om assignment of intervention leaders and by process measurement data OBJECTIVE Research ers continue to try to develop effective teen tobacco use prevention and cessation programs . Three previous school clinic-based studies established the efficacy of Project EX for teen smoking cessation . This fourth study adapts Project EX to the classroom context . This paper reports the findings based on pretest and posttest surveys conducted immediately prior and post-intervention . METHODS An eight-session classroom-based curriculum was developed and tested with a r and omized controlled trial that involved a total of 1097 students in six program and six control continuation high schools . Program-specific knowledge and smoking measures were assessed at both the pretest and posttest surveys , and were used to evaluate the program 's effect on the immediate outcomes . The immediate outcomes effects were analyzed with multi-level r and om coefficients models . RESULTS Program students provided favorable process ratings of the overall program and each session . Compared with the students in the control condition , students in the program condition showed a greater change in correct knowledge responses from pretest to posttest ( beta=+5.5 % , p=0.0003 ) . Students in the program condition also experienced a greater reduction in weekly smoking ( beta=-6.9 % , p=0.038 ) , and intention for smoking in the next 12 months ( beta=-0.21 in 5-level scale , p=0.023 ) . CONCLUSIONS EX-4 immediate outcome results revealed favorable student responses to the program , increases in knowledge , and decreases in smoking relative to a st and ard care control condition PURPOSE To describe smoking initiation , and to investigate factors that predict the early initiation of smoking in schoolchildren using a longitudinal approach . METHODS A prospect i ve study of smoking habits of children from the third and fourth grade s through the eighth and ninth grade s. The initial study population was 1970 ; 79.8 % were white and 20.2 % were African-American . Children were classified as " nonsmokers , " " experimental smokers , " or " current smokers " at five time points over 6 years . Multivariate regression models examined relationships of demographic and developmental factors with smoking initiation . RESULTS Experimental smoking increased from 4 % at Grade s 3 - 4 to 42 % at Grade s 8 - 9 , and current smoking prevalence rose from 0.4 % to 9 % over the same period . The mean age of initiation of smoking was 12.3 years . Smoking initiation ( experimental smoking ) was significantly different by racial group , socioeconomic status ( SES ) , and pubertal development . White children and those of low SES were more likely to be experimental smokers , and also started earlier than African-American children and children of high SES . Once they started , white children advanced more rapidly to become current smokers . Boys had a higher prevalence of experimental smoking than girls at all time points . Children in rural areas were more likely than urban children to start smoking after age 12 years . Children who were at a higher pubertal stage than their peers were also more likely to experiment with smoking . CONCLUSIONS Race , SES , and pubertal stage are important predictors of initiation of smoking in schoolchildren . This study indicates a need for smoking prevention classes in elementary and middle school , especially in areas with large numbers of white and low-SES youth . Also , smoking cessation programs , as well as smoking prevention classes , would be useful for middle school and high school students To evaluate a multicultural smoking prevention curriculum , 16 schools were r and omized to receive the multicultural curriculum or a st and ard curriculum and program effects on 1-year smoking initiation among 1430 never smokers were assessed . Hispanic boys who received the multicultural curriculum were less likely to initiate smoking than were those who received the st and ard curriculum ; effects were insignificant among other groups . The prevention effect among Hispanic boys is encouraging , but additional research is needed to improve prevention effects among other groups We conducted a study of the effectiveness of an educational intervention design ed to modify risk factors associated with coronary heart disease among 3388 children in 37 schools in two demographically dissimilar areas ( the Bronx and Westchester County ) in and around New York City . Schools within each area were r and omly assigned to either intervention or nonintervention groups . In schools targeted for intervention , children in the fourth through eighth grade s were taught a teacher-delivered curriculum focusing on diet , physical activity , and cigarette smoking . Risk-factor levels were measured in all schools at base line and at four follow-up points . A total of 1769 of the children qualified for analysis of the intervention effect . After five years , the net mean change in plasma levels of total cholesterol was -1.7 mg per deciliter per year ( -0.04 mmol per liter ) ( 95 percent confidence interval , -2.7 to -0.7 mg per deciliter [ -0.07 to -0.02 mmol per liter ] ) in the Westchester County schools , or -8.5 mg per deciliter ( -0.22 mmol per liter ) ( 5.1 percent ) over a period of five years . In the schools in the Bronx , the net mean change was -1.0 mg per deciliter per year ( -0.03 mmol per liter ) ( 95 percent confidence interval , -2.3 to + 0.3 mg per deciliter [ -0.06 to + 0.01 mmol per -2.3 to + 0.3 mg per deciliter [ -0.06 to + 0.01 mmol per liter ] ) , or -5.0 mg per deciliter ( -0.13 mmol per liter ) ( 2.9 percent ) over a period of five years . Favorable trends in dietary intake and health knowledge were also observed , whereas the other targeted risk factors were not significantly altered . If these findings can be replicated , this will suggest that educational programs to modify coronary risk factors are feasible and may have a favorable ( albeit small ) effect on blood levels of cholesterol in children Mobilising Youth for Tobacco-Related Initiatives in India ( Project MYTRI ) is a r and omized community trial to prevent tobacco use among students in Grade s 6 through 9 in 32 private and government schools in Delhi and Chennai , India ( N = 12,484 ) . The project is a partnership between research ers and practitioners in the United States and India . This article describes the steps that were carried out to ensure that prior effective programs are appropriate and applicable to India . These steps involve ( a ) developing a conceptual behavioral intervention model , ( b ) ensuring the appropriateness of the model for urban India , ( c ) developing intervention strategies that modify factors in the model , ( d ) implementing the MYTRI program with more than 5,000 students , and ( e ) evaluating the process and outcomes of the intervention . Data to date suggest that this process has been successful , including high participation rates , teacher perceptions of appropriateness , and agreements for further implementation National survey data indicate that illicit drug use has steadily increased among American adolescents since 1992 . This upward trend underscores the need for identifying effective prevention approaches capable of reducing the use of both licit and illicit drugs . The present study examined long-term follow-up data from a large-scale r and omized prevention trial to determine the extent to which participation in a cognitive-behavioral skills-training prevention program led to less illicit drug use than for untreated controls . Data were collected by mail from 447 individuals who were contacted after the end of the 12th grade , 6.5 years after the initial pretest . Results indicated that students who received the prevention program ( Life Skills Training ) during junior high school reported less use of illicit drugs than controls . These results also support the hypothesis that illicit drug use can be prevented by targeting the use of gateway drugs such as tobacco and alcohol OBJECTIVE This study evaluated the efficacy of a version of Project EX that was adapted for implementation in the classroom context ( Project EX-4 ) . This paper reports the program outcomes based on pretest , six-month , and one-year follow-up surveys . METHODS An 8 session classroom-based curriculum was tested with a clustered r and omized controlled trial that involved a total of 1097 students in 6 program and 6 control alternative high schools . Weekly and monthly smoking was assessed at the three time points . Outcome effects were analyzed with multi-level r and om coefficients models . RESULTS Students in the program condition experienced a greater reduction in weekly smoking and monthly smoking , at 6- and -12-month follow-ups . The net change varied between -5.1 % and -7.6 % , comparing the program condition to the control condition . CONCLUSIONS The implementation of Project EX in a classroom setting produced decreases in smoking among students in the program , relative to those in the st and ard care control condition . It is likely that a classroom-based smoking prevention/cessation program can lead to lower overall smoking prevalence than a cessation program that is implemented in a school-based smoking cessation clinic format This paper describes development , over a five-year period , of the Hunter Region Health Promoting Schools Project in New South Wales ( NSW ) , Australia . The project implemented the principles and philosophy of the Health Promoting Schools concept and evaluated its effectiveness using a r and omized controlled trial involving 22 public secondary schools . An overview of the preliminary intervention model based on the health promoting schools philosophy and trialed in a pilot study is provided . The authors also outline barriers to , and difficulties in , implementing the philosophically based intervention model in the secondary school setting . The current intervention approach , which evolved over five years , is described in relation to the roles played by project team members and school communities . In addition , the authors outline guiding principles arising from the new approach which facilitated adoption of health promotion strategies in secondary school setting The present study provides an implementation , process , and immediate outcomes evaluation of the classroom component of Project Towards No Drug Abuse ( TND ) . This project involves development and evaluation of a school-based drug abuse prevention curriculum for continuation high school youth , who are at relatively high risk for drug abuse . Three r and omized conditions were evaluated : a st and ard care , classroom only , and classroom plus school-as-community . The latter condition was an enhanced school-based condition which involved outside-of-classroom meetings and activities . Implementation was high in both program conditions even though this was a higher risk context . Process evaluation data were favorable and did not vary between the two program conditions . Immediate outcomes data ( knowledge ) was higher in the two program conditions than in the st and ard care condition . Regarding the classroom program , addition of extra-classroom activities does not appear to alter the quality of delivery of the program The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multisite intervention research study that builds on significant progress made in school health education research in the 1980s . The study has three phases : Phase I deals with study design , intervention , and measurement development , Phase II involves the main trial in 96 schools in four states , and Phase III focuses on analysis . The intervention program targets third-fifth grade students and focuses on multiple cardiovascular health behaviors , including eating habits , physical activity , and cigarette smoking . Classroom curricula , school environmental change , and family involvement programs are developed for each grade level and behavioral focus . This paper describes Phase II of CATCH with a rationale for cardiovascular health promotion with youth . The process of change that appears to be necessary for school-based health promotion and that will be tested in CATCH are presented as a framework to guide these efforts Purpose . The Child and Adolescent Trial for Cardiovascular Health is a multi-site study of a school-based intervention design ed to reduce or prevent the development of risk factors for cardiovascular disease . The goal was to change ( or prevent ) related risk behaviors and the psychosocial variables that theoretically influence those behaviors . Design . A nested design was used in which schools served as the primary unit of analysis . Twenty-four schools participated at each of four sites ( Austin , San Diego , Minneapolis , and New Orleans ) . Each site had 10 control and 14 intervention schools . Setting and Subject . Ninety-six schools ( with more than 6000 students ) in the four sites were r and omized to three treatment conditions : control , school-based interventions , and school-plus-family interventions . The sample included approximately equal numbers of males and females and was 67.5 % white , 13.9 % African-American , 13.9 % Hispanic , and 4.7 % other . Measures . The psychosocial determinants measured included improvements in dietary knowledge , intentions , self-efficacy , usual behavior , perceived social reinforcement for healthy food choices , and perceived reinforcement and self-efficacy for physical activity . Results . The findings indicated significant improvements in all the psychosocial determinants measured ( p < .0001 ) . The results revealed a greater impact in the school-plus-family intervention schools for two determinants , usual dietary behavior and intentions to eat heart-healthy foods . Conclusions . These findings support theory-based interventions for changing selected psychosocial determinants of cardiovascular disease risk behavior among children Adolescent smoking prevalence is usually assessed via self-complete question naires . However , concern has been expressed about the validity of such self-report . One approach to increase validity involves the threat of biological validation , known as the bogus pipeline method (BPL).This study aim ed to assess the effects of BPL , using an expired air carbon monoxide monitor , and of question naire anonymity on student smoking self-report data . High school students ( n=801 ) were r and omly allocated to one of four conditions : anonymous question naire+BPL , named question naire+BPL , anonymous question naire without BPL and named question naire without BPL . Overall , 37 % of students agreed that question naires were a good way to obtain honest answers . In a logistic regression analysis , students in the BPL condition had significantly higher odds of reporting weekly smoking ( OR=1.83 95 % CI 1.27 - 2.65 ) and monthly smoking ( OR=1.66 95 % CI 1.21 - 2.28 ) but not of lifetime smoking compared with non-BPL students . Students in the named question naire condition had a significantly higher odds of reporting lifetime smoking ( OR=1.49 95 % CI 1.08 - 2.04 ) compared with anonymous students . Studies assessing current smoking patterns in adolescents should consider incorporating a BPL method Project EX is an eight-session teen school-based clinic tobacco use cessation program that involves the inclusion of enjoyable , motivating activities ( " games , " " talk show , " and alternative medicine-type ) to try to enhance quit rates among youth . This clinic program was tested in a three-group experimental design : clinic-only , clinic plus a school-as-community ( SAC ) component , and st and ard care control . Eighteen schools were assigned to the three conditions using a r and omized block design . A total of 335 smokers participated in the study , making this the largest controlled teen smoking cessation field trial conducted to date . Seventeen percent of the smokers enrolled in the clinics had reports of having quit smoking for at least the last 30 days at 3-month follow-up ( 5 months after the program quit day ) , compared to only 8 % of the control condition smokers over than same time period . The Project EX clinic component appears to be an effective means of tobacco use cessation among teens BACKGROUND The Good Behavior Game ( GBG ) is a classroom behavior management strategy focused on socializing children to the role of student and aim ed at reducing early aggressive , disruptive behavior , a confirmed antecedent to service use . The GBG was tested in a r and omized field trial in 19 elementary schools with two cohorts of children as they attended first and second grade s. This article reports on the impact of the GBG on service use through young adulthood . METHODS Three or four schools in each of five urban areas were matched and r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) an intervention aim ed at academic achievement , or ( 3 ) the st and ard program of the school system . Children were assigned to classrooms to ensure balance , and teachers and classrooms were r and omly assigned to intervention conditions . RESULTS This study provides evidence of a positive impact of a universal preventive intervention on later service use by males , although not by females , for problems with emotions , behavior , or drugs or alcohol . For both cohorts , males in GBG classrooms who had been rated as highly aggressive , disruptive by their teachers in the fall of first grade had a lower rate of school-based service use than their counterparts in control classrooms . REPLICATION : The design employed two cohorts of students . Although both first- and second- grade teachers received less training and support with the second cohorts of students than with the first cohort , the impact of GBG was similar across both cohorts This article reports adolescent substance use outcomes of universal family and school preventive interventions 5(1/2 ) years past baseline . Participants were 1677 7th grade students from schools ( N=36 ) r and omly assigned to the school-based Life Skills Training plus the Strengthening Families Program : For Parents and Youth 10 - 14 ( LST+SFP 10 - 14 ) , LST-alone , or a control condition . Self-reports were collected at baseline , 6 months later following the interventions , then yearly through the 12th grade . Measures included initiation-alcohol , cigarette , marijuana , and drunkenness , along with a Substance Initiation Index (SII)- and measures of more serious use-frequency of alcohol , cigarette , and marijuana use , drunkenness frequency , monthly poly-substance use , and advanced poly-substance use . Analyses ruled out differential attrition . For all substance initiation outcomes , one or both intervention groups showed significant , positive point-in-time differences at 12th grade and /or significant growth trajectory outcomes when compared with the control group . Although no main effects for the more serious substance use outcomes were observed , a higher-risk sub sample demonstrated significant , positive 12th grade point-in-time and /or growth trajectory outcomes for one or both intervention groups on all measures . The observed pattern of results likely reflects a combination of predispositions of the higher-risk sub sample , the timing of the interventions , and baseline differences between experimental conditions favoring the control group Purpose . This study examined whether brief intervention strategies founded on the Behavior-Image Model and addressing positive images of college and career success could be potentially efficacious in impacting multiple health habits of high-risk adolescents transitioning into adulthood . Design . Participants were stratified by grade level and drug use and individually r and omized to one of the three Plan for Success interventions , with baseline and 1 month postintervention data collection s. Setting . A large , relatively diverse suburban school in northeast Florida . Subjects . A total of 375 11th and 12th grade students participated during the spring semester 2006 . Intervention . Three interventions studied included : ( 1 ) Goal Survey , ( 2 ) Goal Survey plus Contract , or ( 3 ) Goal Survey plus Consult . Measures . Outcome measures included multiple health risk , health promotion , and personal development behaviors , as well as image and belief measures . Analysis . Repeated- measures MANOVAs and ANOVAs were used to examine intervention effects . Results . MANOVAs were significant for alcohol use , F(4,328 ) = 6.33 , p = .001 ; marijuana use , F(4,317 ) = 3.72 , p = .01 ; exercise , F(3,299 ) = 4.28 , p = .01 ; college preparation , F(2,327 ) = 6.26 , p = .001 ; and career preparation , F(2,329 ) = 6.17 , p = .001 , with most behaviors improving over time , whereas group-by-time interaction effects were found for nutrition habits , F(6,652 ) = 2.60 , p = .02 ; and career preparation , F(4,658 ) = 3.26 , p = .01 , favoring the consultation . Conclusion . Brief interventions founded on the Behavior-Image Model may have potential to improve selected health and personal development habits among older adolescents |
11,226 | 24,534,357 | Small changes in diet , physical activity , knowledge , and self-efficacy were shown ; however , few results were sustained long term .
With further research and evidentiary support , this approach to obesity-related nutrition education has the potential to be successful | PURPOSE The purpose of this systematic review was to evaluate recent research regarding the use of computer-based nutrition education interventions targeting adolescent overweight and obesity . | OBJECTIVES Motivating adolescents to adopt proper nutrition and physical activity behaviors is important in this nation 's fight to prevent obesity and chronic diseases . This study was conducted to determine which health education delivery method would elicit a greater behavior change . METHOD The intervention was conducted in three schools ( control , computer-based , and traditional education ) . RESULTS Students who received the computer-based intervention showed increased knowledge ( p<0.001 ) , physical activity ( p=0.001 ) , self-efficacy ( p<0.001 ) , and social support ( p<0.001 ) , and decreased meals skipped ( p<0.001 ) . CONCLUSION The computer-based group showed more positive behavior changes . However , future programs may be enhanced by including group discussion and individual feedback PURPOSE To examine the feasibility and efficacy of a theory-driven and family-based program delivered online to promote healthy lifestyles and weights in Chinese American adolescents . METHODS A r and omized controlled study of a web-based intervention was developed and conducted in 54 Chinese American adolescents ( ages , 12 - 15 years ) and their families . Data on anthropometry , blood pressure , dietary intake , physical activity , and knowledge and self-efficacy regarding physical activity and nutrition were collected at baseline and 2 , 6 , and 8 months after the baseline assessment . Data were analyzed using linear mixed modeling . RESULTS The intervention result ed in significant decreases in waist-to-hip ratio and diastolic blood pressure and increases in vegetable and fruit intake , level of physical activity , and knowledge about physical activity and nutrition . CONCLUSION This web-based behavior program for Chinese American adolescents and their families seems feasible and effective in the short-term . Long-term effects remain to be determined . This type of program can be adapted for other minority ethnic groups who are at high-risk for overweight and obesity and have limited access to programs that promote healthy lifestyles PURPOSE To compare the effectiveness of two school-based internet obesity prevention programs for diverse adolescents on body mass index ( BMI ) , health behaviors , and self-efficacy , and to explore moderators of program efficacy . It was hypothesized that the addition of coping skills training to a health education and behavioral support program would further enhance health outcomes . METHODS A r and omized clinical trial with cluster r and omization by class and repeated measures with follow-up at 3 and 6 months was conducted ( n = 384 ) . BMI was assessed by use of st and ard procedures . Sedentary behavior , physical activity , nutrition behavior , self-efficacy , and satisfaction were assessed with self-report measures . Data analysis consisted of mixed model analyses with autoregressive covariance structure for repeated data by use of intent-to-treat procedures . RESULTS The mean age of students was 15.31 years ( ±0.69 ) , with a mean BMI of 24.69 ( ±5.58 ) . The majority were girls ( 62 % ) and of diverse race/ethnicity ( 65 % non-white ) . There were no significant differences between groups on any outcomes and no change in BMI over time . There were significant improvements in health behaviors ( sedentary behavior , moderate and vigorous physical activity , healthy eating , fruit and vegetable intake , sugar beverages , and junk food intake ) and self-efficacy . Gender and lesson completion moderated select health outcomes . There was excellent participation and high satisfaction with the programs . CONCLUSIONS School-based internet obesity prevention programs are appealing to adolescents and improve health behaviors . The differential effect of coping skills training may require longer follow-up Background : The positive effects of computer-tailored dietary fat intake interventions have been demonstrated in adults , but few studies have investigated the impact on adolescents . Purpose : The purpose is to evaluate the acceptability , feasibility and effectiveness of a computer-tailored dietary fat intake education program for adolescents . Methods : A r and om sample of 10 schools , 5 with general and 5 with technical-vocational education programs , were selected to participate . In each of the 10 schools , 2 classes of 7th grade rs were r and omly assigned to the intervention ( n=153 ) or control ( no-intervention , n=151 ) condition . Students were exposed once in class to a 50-min theory-based computer-tailored dietary fat intake intervention . Question naires were completed 1 week before ( food frequency question naire for dietary fat intake + psychosocial determinants ) and 3 months after ( process evaluation + food frequency question naire for dietary fat intake + psychosocial determinants ) the intervention . Results : About one in three students evaluated the intervention as interesting ( 34 % ) , novel ( 38 % ) , personally relevant ( 26 % ) , credible ( 34 % ) , and correct ( 38 % ) . Half of the students evaluated the intervention messages to be too long , and one fourth did not read the intervention messages . A decrease in dietary fat consumption was shown in girls enrolled in technical-vocational schools ( F=3.5 , p≤.05 ) and in boys and girls undertaking general education who reported to have read the intervention messages ( F=3.6 , p≤.05 ) ; however , no intervention effects were detected for the total sample . Conclusions : Further improvements to the intervention for use in adolescents should be evaluated . Given that a positive impact was shown in most adolescents and that a computer-tailored dietary fat intake education program has the capability of reaching large groups at low cost , this study shows that using such interventions in adolescents has potential OBJECTIVE To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grade s 6 to 8 . DESIGN R and omized , controlled field trial with 5 intervention and 5 control schools . Outcomes were assessed using preintervention ( fall 1995 ) and follow-up measures ( spring 1997 ) , including prevalence , incidence , and remission of obesity . PARTICIPANTS A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities . INTERVENTION Students participated in a school-based interdisciplinary intervention over 2 school years . Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education . Sessions focused on decreasing television viewing , decreasing consumption of high-fat foods , increasing fruit and vegetable intake , and increasing moderate and vigorous physical activity . MAIN OUTCOME MEASURES Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles . Because schools were r and omized , rather than students , the generalized estimating equation method was used to adjust for individual-level covariates under cluster r and omization . RESULTS The prevalence of obesity among girls in intervention schools was reduced compared with controls , controlling for baseline obesity ( odds ratio , 0.47 ; 95 % confidence interval , 0.24 - 0.93 ; P = .03 ) , with no differences found among boys . There was greater remission of obesity among intervention girls vs. control girls ( odds ratio , 2.16 ; 95 % confidence interval , 1.07 - 4.35 ; P = .04 ) . The intervention reduced television hours among both girls and boys , and increased fruit and vegetable consumption and result ed in a smaller increment in total energy intake among girls . Reductions in television viewing predicted obesity change and mediated the intervention effect . Among girls , each hour of reduction in television viewing predicted reduced obesity prevalence ( odds ratio , 0.85 ; 95 % confidence interval , 0.75 - 0.97 ; P = .02 ) . CONCLUSION Planet Health decreased obesity among female students , indicating a promising school-based approach to reducing obesity among youth BACKGROUND Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population , but their causal relation remains unclear . OBJECTIVE The objective of this study was to examine how changes in beverage consumption affect weight change among adults . DESIGN This was a prospect i ve study of 810 adults participating in the PREMIER trial , an 18-mo r and omized , controlled , behavioral intervention trial . Measurements ( weight , height , and 24-h dietary recall ) were made at baseline , 6 mo , and 18 mo . RESULTS Baseline mean intake of liquid calories was 356 kcal/d ( 19 % of total energy intake ) . After potential confounders and intervention assignment were controlled for , a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg ( 95 % CI : 0.11 , 0.39 ; P < 0.001 ) at 6 mo and of 0.24 kg ( 95 % CI : 0.06 , 0.41 ; P = 0.008 ) at 18 mo . A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss . Of the individual beverages , only intake of sugar-sweetened beverages ( SSBs ) was significantly associated with weight change . A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg ( 95 % CI : 0.11 , 0.82 ; P = 0.006 ) at 6 mo and of 0.65 kg ( 95 % CI : 0.22 , 1.09 ; P = 0.003 ) at 18 mo . CONCLUSIONS These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain . This trial was registered at clinical trials.gov as NCT00000616 OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time OBJECTIVE . This study examined the efficacy of an Internet-facilitated intervention for weight maintenance and binge eating in adolescents . METHODS . A total of 105 adolescent male and female high school students at risk for overweight ( mean age : 15.1 ± 1.0 years ) were r and omly assigned to a 16-week online intervention , StudentBodies2-BED ( n = 52 ) , or the wait-list control group ( n = 53 ) . RESULTS . Participants in the StudentBodies2-BED group had significantly lower BMI z scores and BMI from baseline assessment to follow-up assessment , compared with the wait-list control group . In addition , significant reductions in objective binge episodes and subjective binge episodes from baseline assessment to posttreatment assessment and from baseline assessment to follow-up assessment were observed among StudentBodies2-BED participants . The StudentBodies2-BED group also reported significantly reduced weight and shape concerns from posttreatment assessment to follow-up assessment and from baseline assessment to follow-up assessment . Participants in the StudentBodies2-BED group who engaged in objective overeating or binge eating episodes at baseline assessment experienced a significantly greater reduction in BMI at follow-up assessment , compared with the wait-list control group . CONCLUSIONS . Results suggest that an Internet-facilitated intervention is moderately effective in short-term weight loss and weight maintenance and yields a large reduction in binge eating . This study also demonstrates that weight management and reduction of eating disorder psychopathological features can be achieved simultaneously by using an easily disseminated , Internet-facilitated program OBJECTIVE This study was undertaken to evaluate the efficacy of a skills-based CD-ROM intervention , with and without a parent component , to reduce alcohol use among urban youth at 6-year follow-up . METHOD At recruitment , 513 youths with a mean age of 10.8 years were r and omly assigned to one of three study arms : youth CD-ROM intervention plus parent component , youth CD-ROM intervention only , or control . All youths completed pretest , posttest , and annual follow-up measures . Youths and parents in their respective arms received the initial intervention program between pretest and posttest measures and received booster interventions between each follow-up measure . RESULTS With 80 % sample retention at 6-year follow-up , youths in both intervention arms reported less past-month alcohol and cigarette use and fewer instances of heavy drinking and negative alcohol-related consequences . Despite having similar numbers of drinking peers as youths in the control arm , youths in both intervention arms reported greater alcohol-refusal skills . Only past-month cigarette use differed between the two intervention arms , with youths in the intervention-plus-parent-component arm smoking less than youths in the CD-ROM intervention-only arm . CONCLUSIONS Six years after initial intervention , youths who received a culturally tailored , skills-based prevention program had reduced alcohol use and lower rates of related risky behaviors than youths in the control arm OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research BACKGROUND This study reports on effectiveness trial outcomes of Health in Motion , a computer tailored multiple behavior intervention for adolescents . METHODS Using school as level of assignment , students ( n=1800 ) from eight high schools in four states ( RI , TN , MA , and NY ) were stratified and r and omly assigned to no treatment or a multi-media intervention for physical activity , fruit and vegetable consumption , and limited TV viewing between 2006 and 2007 . RESULTS Intervention effects on continuous outcomes , on movement to action and maintenance stages , and on stability within action and maintenance stages were evaluated using r and om effects modeling . Effects were most pronounced for fruit and vegetable consumption and for total risks across all time points and for each behavior immediately post intervention . Co-variation of behavior change occurred within the treatment group , where individuals progressing to action or maintenance for one behavior were 1.4 - 4.2 times more likely to make similar progress on another behavior . CONCLUSION Health in Motion is an innovative , multiple behavior obesity prevention intervention relevant for all adolescents that relies solely on interactive technology to deliver tailored feedback . The outcomes of the effectiveness trial demonstrate both an ability to initiate behavior change across multiple energy balance behaviors simultaneously and feasibility for ease of dissemination OBJECTIVE Children 's fruit/vegetable intake is still below recommended levels . This study applied Internet-tailored advice for schoolchildren and Internet-supported brief dietary counselling ( with child and parent ) within preventive health care to promote fruit/vegetable intake . SETTING /SUBJECTS The study involved 30 seventh- grade classes ( 16 in the intervention group and 14 in the control group ) with a total of 675 children aged 9 - 12 years , of whom 495 were allowed to participate . DESIGN A cluster-r and omised baseline-post-test experimental design was applied . During school hours , all children completed Internet-administered question naires on fruit/vegetable intake and related determinants . Children in the intervention group received immediate online individually tailored nutrition feedback . For each child in the intervention group , a nurse received information concerning the assessment of fruit/vegetable intake via the Internet to support a 5 min counselling protocol to promote fruit/vegetable intake . Children completed a similar post-test question naire 3 months after the first assessment . Intention-to-treat analyses were conducted using multilevel regression analyses . RESULTS A total of 486 children ( 98 % of 495 ) participated ( 263 in the intervention group , 223 in the control group ) ; 240 child-parent couples in the intervention group attended the counselling . Awareness of inadequate fruit intake ( odds ratio ( OR ) = 3.0 ; 95 % confidence interval ( CI ) = 1.8 - 5.3 ) and knowledge of recommended vegetable intake levels ( OR = 2.7 ; 95 % CI = 1.8 - 4.1 ) were significantly more likely at post-test in the intervention group than in the control group . No significant effects were found on intake or other determinants . CONCLUSIONS A compact , integrated two-component intervention can induce positive changes in knowledge and awareness of intake levels of fruit/vegetables among schoolchildren . To induce changes in intake levels , more comprehensive interventions may be needed OBJECTIVE To investigate use and views of a Web site design ed for weight control . DESIGN Question naire-based evaluation with data collected at baseline , 6 months , and 12 months . SETTING Data were collected as part of a community-based , r and omized controlled trial . PARTICIPANTS Subjects ( n = 111 ) were participants of the intervention arm of a r and omized controlled trial evaluating effectiveness of a Web site design ed for weight control in an obese sample . INTERVENTION Participants were asked to use the intervention Web site for weight control over a 12-month period . MAIN OUTCOME MEASURE(S ) Participants were asked to report their use and views of the Web site . In addition , use of the Web site was automatically recorded on logging onto the Web site . ANALYSIS Descriptive statistics , factor analysis . RESULTS Fifty-nine participants ( 53 % ) reported using the Web site at 6 months , with 32 participants ( 29 % ) still using it at 12 months . The average time spent on the Web site per visit was 21.1 minutes ( SD = 16.6 ) at 6 months and 13.6 minutes ( SD = 9.3 ) at 12 months , with an average number of logons of 15.8 ( SD = 15.2 ) over the trial period . In general , satisfaction scores for the Web site were positive . Scores for ability of the re source to encourage positive behavior change for weight control were marginally negative . Social support sections of the Web site were used least and received the lowest satisfaction ratings . CONCLUSIONS AND IMPLICATION S Despite positive satisfaction scores , use of the re source was limited . It is expected that participants ' limited ability to use the Internet may have limited the use of the re source and consequently reduced the social support available to participants . Future investigation of the views and use patterns of current users of Internet-based weight loss re sources would help inform future development of such tools CONTEXT Weight loss programs on the Internet appear promising for short-term weight loss but have not been studied for weight loss in individuals at risk of type 2 diabetes ; thus , the longer-term efficacy is unknown . OBJECTIVE To compare the effects of an Internet weight loss program alone vs with the addition of behavioral counseling via e-mail provided for 1 year to individuals at risk of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized controlled trial conducted from September 2001 to September 2002 in Providence , RI , of 92 overweight adults whose mean ( SD ) age was 48.5 ( 9.4 ) years and body mass index , 33.1 ( 3.8 ) . INTERVENTIONS Participants were r and omized to a basic Internet ( n = 46 ) or to an Internet plus behavioral e-counseling program ( n = 46 ) . Both groups received 1 face-to-face counseling session and the same core Internet programs and were instructed to su bmi t weekly weights . Participants in e-counseling su bmi tted calorie and exercise information and received weekly e-mail behavioral counseling and feedback from a counselor . MAIN OUTCOME MEASURES Measured weight and waist circumference at 0 and 12 months . RESULTS Intent-to-treat analyses showed the behavioral e-counseling group lost more mean ( SD ) weight at 12 months than the basic Internet group ( -4.4 [ 6.2 ] vs -2.0 [ 5.7 ] kg ; P = .04 ) , and had greater decreases in percentage of initial body weight ( 4.8 % vs 2.2 % ; P = .03 ) , body mass index ( -1.6 [ 2.2 ] vs -0.8 [ 2.1 ] ; P = .03 ) , and waist circumference ( -7.2 [ 7.5 ] vs -4.4 [ 5.7 ] cm ; P = .05 ) . CONCLUSION Adding e-mail counseling to a basic Internet weight loss intervention program significantly improved weight loss in adults at risk of diabetes OBJECTIVE To investigate the feasibility and impact of the Food-O-Meter , an Internet-based computer-tailored nutrition intervention in adolescents . DESIGN Participants in the intervention condition received the computer-tailored advice at baseline and at 1 month , those in the control condition received st and ardised advice . Effects were evaluated at 1 month ( n 621 ) and at 3 months ( n 558 ) using multi-level modelling . SETTING Secondary schools in six European cities . Adolescents accessed the intervention in the school computer room under the supervision of teachers . SUBJECTS Classes with students aged 12 - 17 years in the schools participating in the HELENA ( Healthy Lifestyle in Europe by Nutrition in Adolescence ) cross-sectional study were r and omised into intervention and control schools . RESULTS In most participating centres the intervention was feasible and generally well appreciated , especially by girls . Technical problems and lack of motivation of the teachers hindered implementation in some centres . Overweight adolescents had higher scores for reading and using the advice than normal weight adolescents . After 1 month adolescents receiving the st and ardised advice reported an increase in fat intake , while fat intake in the intervention condition was stable ( F = 4·82 , P < 0·05 ) . After 3 months , there was a trend in the total group for an intervention effect of the tailored advice on fat intake ( F = 2·80 , P < 0·10 ) . In the overweight group there was a clear positive effect ( F = 5·76 , P < 0·05 ) . CONCLUSIONS The Food-O-Meter should be developed further . The results were modest but clear for percentage energy from fat , specifically in the overweight group . Adaptations based on new research are needed to enhance the reliability and effectiveness of the intervention OBJECTIVE To evaluate the short- and long-term results of FATaintPHAT , a Web-based computer-tailored intervention aim ing to increase physical activity , decrease sedentary behavior , and promote healthy eating to contribute to the prevention of excessive weight gain among adolescents . DESIGN Cluster r and omized trial with an intervention group and a no-intervention control group . SETTING Twenty schools in the Netherl and s. PARTICIPANTS A total of 883 students ( aged 12 - 13 years ) . INTERVENTION The FATaintPHAT ( VETisnietVET in Dutch ) Web-based computer-tailored intervention . OUTCOME MEASURES Self-reported behaviors ( diet , physical activity , sedentary behavior ) and pedometer counts were measured at baseline and at 4-month and 2-year follow-up ; body mass index ( BMI ) , waist circumference , and fitness were measured at baseline and at 2-year follow-up . Descriptive and multilevel regression analyses were conducted among the total study population and among students not meeting behavioral recommendations at baseline ( students at risk ) . RESULTS The complete case analyses showed that FATaintPHAT had no effect on BMI and waist circumference . However , the intervention was associated with lower odds ( 0.54 ) of drinking more than 400 mL of sugar-sweetened beverages per day and with lower snack intake ( β = -0.81 snacks/d ) and higher vegetable intake ( β = 19.3 g/d ) but also with a lower step count ( β = -10 856 steps/wk ) at 4-month follow-up . In addition , among students at risk , FATaintPHAT had a positive effect on fruit consumption ( β = 0.39 g/d ) at 4-month follow-up and on step count ( β = 14 228 steps/wk ) at 2-year follow-up but an inverse effect on the odds of sports participation ( odds ratio , 0.45 ) at 4-month follow-up . No effects were found for sedentary behavior . CONCLUSION The FATaintPHAT intervention was associated with positive short-term effects on diet but with no effects or unfavorable effects on physical activity and sedentary behavior Objective : This r and omized controlled trial tested the efficacy of an internetbased lifestyle behavior modification program for weight management in African-American girls . Design : African-American girls were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . The behavioral intervention included internet counseling and was highly interactive . The control intervention was a passive ( non-interactive ) educational program . Parents were also participants in the study . Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention . Subjects : The study enrolled 57 African-American adolescent girls ( ages 11 to 15 years ) who were overweight or obese and had at least one biological parent who was obese [ body mass index ( BMI ) > 30 kg/m2 ] . Of the 57 participants , 50 ( 88 % ) completed the 6-month trial . Measurements : Outcome data , including BMI , body weight , body composition , dietary intake , and weight loss behaviors were collected at baseline and 6-months later . A computer server tracked utilization of the websites . Participation in the program was measured by number of “ hits ” on the website . Results : Compared to the control condition , adolescents in the behavioral treatment lost more body fat ( group difference = 1.6 % body fat ) and parents lost significantly more body weight ( group difference = 2.1 kg ) . Utilization of the behavioral website by adolescents and parents was associated with positive outcome . Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group . Conclusion : An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents The rising tide of obesity erodes the health of youths and many times results in adult obesity . The purpose of this investigation was to examine the effectiveness of an eight-session health promotion/transtheoretical model Internet/video-delivered intervention to increase physical activity and reduce dietary fat among low-income , culturally diverse , seventh- grade students . Those who completed more than half the sessions increased exercise , t ( 103 ) = -1.99 , p = .05 , and decreased the percentage of dietary fat , t ( 87 ) = 2.73 , p = .008 . Responses to the intervention by stage of change , race , and income are examined There is ample evidence that printed , computer-tailored nutrition education is a more effective tool for motivating people to change to healthier diets than general nutrition education . New technology is now providing more advanced ways of delivering tailored messages , e.g. via the World Wide Web ( WWW ) . Before disseminating a tailored intervention via the web , it is important to investigate the potential of web-based tailored nutrition education . The present study investigated the immediate impact of web-based computer-tailored nutrition education on personal awareness and intentions related to intake of fat , fruit and vegetables . A r and omized controlled trial , with a pre-test-post-test control group design was conducted . Significant differences in awareness and intention to change were found between the intervention and control group at post-test . The tailored intervention was appreciated better , was rated as more personally relevant , and had more subjective impact on opinion and intentions to change than the general nutrition information . Computer literacy had no effect on these ratings . The results indicate that interactive , web-based computer-tailored nutrition education can lead to changes in determinants of behavior . Future research should be aim ed at longer-term ( behavioral ) effects and the practicability of distributing tailored interventions via the WWW Using a prospect i ve , r and omized , controlled design , we examined the effects of behavioral family-based treatment on percent overweight and growth over 10 years in obese 6- to 12-year-old children . Obese children and their parents were r and omized to three groups that were provided similar diet , exercise , and behavior management training but differed in the reinforcement for weight loss and behavior change . The child and parent group reinforced parent and child behavior change and weight loss , the child group reinforced child behavior change and weight loss , and the nonspecific control group reinforced families for attendance . Children in the child and parent group showed significantly greater decreases in percent overweight after 5 and 10 years ( -11.2 % and -7.5 % , respectively ) than children in the nonspecific control group ( + 7.9 % and + 14.3 % , respectively ) . Children in the child group showed increases in percent overweight after 5 and 10 years ( + 2.7 % and + 4.5 % , respectively ) that were midway between those for the child and parent and nonspecific groups and not significantly different from either . At 10 years , child height was related strongly to the height of the parent of the same sex ( r = .78 children were 1.8 cm taller than their parents , with no differences in height between groups As access to computers and the Internet by the low-income population is increasing and the " digital divide " is slowly diminishing , other methods of delivering nutrition information to this audience are evolving . This r and omized , block equivalence trial sought to determine whether web-based nutrition education could result in equivalent nutrition-related behavior outcomes when compared with traditional in-person nutrition education in low-income adults . A convenience sample of low-income adults ( n=123 ) was r and omized to receive in-person education ( n=66 ) or web-based education ( n=57 ) in a community setting within 14 counties of Indiana from April through December 2010 . The web-based group received three nutrition education lessons ( eg , fruits and vegetables , Nutrition Facts label reading , and whole grains ) design ed to replicate lessons received by the in-person group . Lessons were developed using Kolb 's Learning Styles and Experiential Learning Model . Self-reported nutrition-related behaviors were assessed using a previously vali date d survey for low-income adults . Most nutrition-related behavior outcomes ( eg , fruit , vegetable , whole-grain intake , Nutrition Facts label use , breakfast , and meal-planning frequency ) improved significantly ( P<0.05 ) from pre to post within both groups , meaning that each intervention was effective . When these nutrition-related behavior improvements were compared between groups , the changes were statistically equivalent ( P>0.05 ) , except for one question about use of the Nutrition Facts label . Therefore , web-based nutrition education can lead to favorable and equivalent nutrition-related changes when compared with in-person delivery . Most ( 83 % ) web-based participants also reported willingness to use the website again . Future application of web-based interventions for low-income population s could broaden delivery reach , increase frequency and length of contacts , and possibly decrease costs The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored PURPOSE This r and omized clinical trial examined longitudinal outcomes from an alcohol abuse prevention program aim ed at urban youths . METHODS Study participants were an ethnically and racially heterogeneous sample of early adolescents , recruited from community-based agencies in greater New York City and its environs . Once they assented to study participation and gained parental permission , youths were divided into three arms : youth intervention delivered by CD-ROM ( CD ) , the same youth intervention plus parent intervention ( CD(P ) ) , and control . Once all youths completed baseline measures , those in CD and CD(P ) arms received a computerized 10-session alcohol abuse prevention program . Parents of youths in the CD(P ) arm received supplemental material s to support and strengthen their children 's learning . All youths completed postintervention and annual follow-up measures , and CD- and CD(P)-arm participants received annual booster intervention sessions . RESULTS Seven years following postintervention testing and relative to control-arm youths , youths in CD and CD(P ) arms reported less alcohol use , cigarette use , binge drinking , and peer pressure to drink ; fewer drinking friends ; greater refusal of alcohol use opportunities ; and lower intentions to drink . No differences were observed between CD and CD(P ) arms . CONCLUSIONS Study findings lend support to the potential of computerized , skills-based prevention programs to help urban youth reduce their risks for underage drinking |
11,227 | 29,155,436 | Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy ( low- quality evidence ) .
One small r and omized controlled trial provided no robust evidence for which dosing schedule of alglucosidase alfa was more effective to treat infantile-onset Pompe disease . | BACKGROUND Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase ( GAA ) .
Current treatment involves enzyme replacement therapy ( with recombinant human alglucosidase alfa ) and symptomatic therapies ( e.g. to control secretions ) .
Children who are cross-reactive immunological material (CRIM)-negative require immunomodulation prior to commencing enzyme replacement therapy .
Enzyme replacement therapy was developed as the most promising therapeutic approach for Pompe disease ; however , the evidence is lacking , especially regarding the optimal dose and dose frequency .
OBJECTIVES To assess the effectiveness , safety and appropriate dose regimen of enzyme replacement therapy for treating infantile-onset Pompe disease . | Background Infantile Pompe disease ( glycogen storage disease type 2 ) is a fatal disorder caused by deficiency of acid α-glucosidase . This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle . The disease is characterized by profound hypotonia , poor growth , organomegaly , and cardiomegaly . Severe hypertrophic cardiomyopathy often is present in early infancy , and most patients die of cardiac or respiratory failure in the first year of life . This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy ( ERT ) . Methods Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA ( rhGAA ) for 1 year . Cardiac monitoring included echocardiography , electrocardiograms ( ECGs ) , chest radiographs , and clinical cardiac evaluation at 4 , 8 , 12 , 24 , 36 , and 52 weeks . At 52 weeks , 6 patients were alive . Results Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT , with near normalization of posterior wall thickness , ventricular mass , and ventricular size . Systolic ventricular function was preserved despite rapid changes in ventricular mass and size . Concomitantly , ECGs documented lengthening of the PR interval and decreased ventricular voltages , whereas chest radiographs documented a decreased cardiothoracic ratio . Symptoms of pulmonary congestion were diminished , and survival was improved . Conclusion The cardiovascular system responds quickly and strikingly to ERT with rhGAA , suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells . Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival Deficiency of acid alpha glucosidase ( GAA ) causes Pompe disease , which is usually fatal if onset occurs in infancy . Patients synthesize a non-functional form of GAA or are unable to form native enzyme . Enzyme replacement therapy with recombinant human GAA ( rhGAA ) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients . We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA . Patients were from the clinical setting and from clinical trials of rhGAA , were 6 months of age , were not invasively ventilated , and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks . Outcome measures included survival , invasive ventilator-free survival , cardiac status , gross motor development , development of antibodies to rhGAA , and levels of urinary Glc(4 ) . Following 52 weeks of treatment , 6/11 ( 54.5 % ) CRIM-negative and 1/21 ( 4.8 % ) CRIM-positive patients were deceased or invasively ventilated ( p<0.0001 ) . By age 27.1 months , all CRIM-negative patients and 4/21 ( 19.0 % ) CRIM-positive patients were deceased or invasively ventilated . Cardiac function and gross motor development improved significantly more in the CRIM-positive group . IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group . CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA . The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein Emerging phenotypes in long-term survivors with Pompe disease on st and ard enzyme replacement therapy ( ERT ) ( alglucosidase alfa 20 mg/kg/2 weeks ) can include patients with worsening motor function . Whether higher doses of ERT improve skeletal function in these patients has not been systematic ally studied . This exploratory , r and omized , open-label , 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa ( 20 mg/kg/week or 40 mg/kg/2 weeks ) in 13 patients with Pompe disease and clinical decline or a lack of improvement on st and ard ERT : late-onset ( n = 4 ) , infantile-onset ( n = 9 ) . Cross-reactive immunologic material assay-negative patients were excluded . Eleven of 13 patients completed the study . Trends for improvement were seen in total gross motor function , but not mobility ; however , 6 ( late-onset , 2 ; infantile-onset , 4 ) of 11 patients ( 55 % ) who met the entry criteria of motor decline ( late-onset , 4 ; infantile-onset , 7 ) showed improvement in motor and /or mobility skills . No between-regimen differences in efficacy emerged . Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline . Both alternative regimens were generally well tolerated . This study was limited by the small sample size , which is not uncommon for small clinical studies of rare diseases . Additionally , the study did not include direct assessment of muscle pathology , which may have identified potential causes of decreased response to ERT . Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline . Controlled studies are needed to clarify the benefits and risks of this strategy Purpose : A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease . Methods : Open-label , multicenter study of IV alglucosidase alfa treatment in 21 infants 3–43 months old ( median 13 months ) with minimal acid α-glucosidase activity and abnormal left ventricular mass index by echocardiography . Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks ( median 120 weeks ) . Survival results were compared with an untreated reference cohort . Results : At study end , 71 % ( 15/21 ) of patients were alive and 44 % ( 7/16 ) of invasive-ventilator free patients remained so . Compared with the untreated reference cohort , alglucosidase alfa reduced the risk of death by 79 % ( P < 0.001 ) and the risk of invasive ventilation by 58 % ( P = 0.02 ) . Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks ; 62 % ( 13/21 ) achieved new motor milestones . Five patients were walking independently at the end of the study and 86 % ( 18/21 ) gained functional independence skills . Overall , 52 % ( 11/21 ) of patients experienced infusion-associated reactions ; 95 % ( 19/20 ) developed IgG antibodies to recombinant human lysosomal acid α-glucosidase ; no patients withdrew from the study because of safety concerns . Conclusions : In this population of infants with advanced disease , biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival . Treatment also improved indices of cardiomyopathy , motor skills , and functional independence OBJECTIVE To conduct an open-label , multinational , multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase ( rhGAA ) in treatment of infantile-onset Pompe disease . STUDY DESIGN We enrolled 8 infant patients who had Pompe disease with GAA activity < 1 % of normal , cardiomyopathy , and hypotonia . In the 52-week initial phase , rhGAA was infused intravenously at 10 mg/kg weekly ; an extension phase continued survivors ' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks . Safety measurements included adverse events , laboratory tests , and anti-rhGAA antibody titers . Efficacy evaluations included survival , ventilator use , echocardiograms , growth , and motor and cognitive function . RESULT After 52 weeks of treatment , 6 of 8 patients were alive , and 5 patients were free of invasive ventilator support . Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition . Five patients acquired new motor milestones ; 3 patients walked independently . Four patients died after the initial study phase ; the median age at death or treatment withdrawal for all patients was 21.7 months , significantly later than expected for patients who were not treated . Treatment was safe and well tolerated ; no death was drug-related . CONCLUSION rhGAA improved ventilator-free survival , cardiomyopathy , growth , and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase . Due to virtual absence of acid alpha-glucosidase , patients with classical infantile Pompe disease develop progressive cardiomyopathy , skeletal muscle weakness and respiratory insufficiency leading to death in early infancy . We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions . Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits . Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival , left ventricular mass index , motor development as well as histologic and biochemical analysis of muscle biopsies . This therapy was in general well-tolerated . There was an overall improvement in left ventricular mass , cardiac function , skeletal muscle function and histological appearance of skeletal muscle |
11,228 | 29,530,309 | Overall the quality of the evidence base remains greatest for LSM and topical repellents , relative to the other VCTs evaluated , although existing evidence indicates that topical repellents are unlikely to provide effective population -level protection against malaria . | BACKGROUND Additional vector control tools ( VCTs ) are needed to supplement insecticide-treated nets ( ITNs ) and indoor residual spraying ( IRS ) to achieve malaria elimination in many setting s. To identify options for exp and ing the malaria vector control toolbox , we conducted a systematic review of the availability and quality of the evidence for 21 malaria VCTs , excluding ITNs and IRS . | BACKGROUND Odour baits can attract host-seeking Anopheles mosquitoes indoors and outdoors . We assessed the effects of mass deployment of odour-baited traps on malaria transmission and disease burden . METHODS We installed solar-powered odour-baited mosquito trapping systems ( SMoTS ) to households on Rusinga Isl and , Lake Victoria , western Kenya ( mean population 24 879 ) , in a stepped-wedge cluster-r and omised trial . All residents in the completed health and demographic surveillance system were eligible to participate . We used the travelling salesman algorithm to assign all households to a cluster ( 50 or 51 geographically contiguous households ) ; nine contiguous clusters formed a metacluster . Initially , no cluster had SMoTS ( non-intervened ) . During the course of the intervention roll-out SMoTS were gradually installed cluster by cluster until all clusters had SMoTS installed ( intervened ) . We generated 27 cluster r and omisations , with the cluster as unit of r and omisation , to establish the order to install the traps in the clusters until all had a SMoTS installed . Field workers and participants were not masked to group allocation . The primary outcome of clinical malaria was monitored through repeated household visits covering the entire population , once before roll-out ( baseline ) and five times throughout the 2-year roll-out . We measured clinical malaria as fever plus a positive result with a rapid diagnostic test . The SolarMal project was registered on the Dutch Trial Register ( NTR 3496 ) . FINDINGS We enrolled 34 041 participants between April 25 , 2012 , and March 23 , 2015 , to 81 clusters and nine metaclusters . 4358 households were provided with SMoTS during roll-out between June 3 , 2013 , and May 16 , 2015 . 23 clinical malaria episodes were recorded in intervened clusters and 33 episodes in non-intervened clusters ( adjusted effectiveness 40·8 % [ 95 % CI -172·8 to 87·1 ] , p=0·5 ) during the roll-out . Malaria prevalence measured by rapid diagnostic test was 29·8 % ( 95 % CI 20·9 - 38·0 ) lower in SMoTS clusters ( prevalence 23·7 % ; 1552 of 6550 people ) than in non-intervened clusters ( prevalence 34·5 % ; 2002 of 5795 people ) . INTERPRETATION The unexpectedly low clinical incidence of malaria during roll-out led to an imprecise estimate of effectiveness from the clinical incidence data . The substantial effect on malaria prevalence is explained by reduction in densities of Anopheles funestus . Odour-baited traps might be an effective malaria intervention . FUNDING COmON Foundation A r and omized , double-blinded , placebo-controlled study was conducted to examine the effect of spatial repellent ( SR ) in households at risk of malaria in Indonesia . Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages , all households were given either metofluthrin or placebo mosquito coils . Weekly blood smear screening and human-l and ing mosquito catches were done throughout the 6 months intervention . Malaria infections occurred in 61 subjects living in placebo households and 31 subjects living in SR coil households , suggesting a 52 % protective effect of SR . Likewise , anopheles indoor human l and ing rates were 32 % lower in homes receiving SR coils . Differences in the malaria attack rate between SR- and placebo-treated homes was significant when not accounting for the effects of clustering . When the analysis was adjusted for intra-cluster correlation , the differences between SR- and placebo-treated homes were not statistically significant . The findings provide evidence of SR public health benefit and support a larger trial statistically powered to detect those effects Background Mosquito coils are the most commonly used household insecticidal product in the world with sales exceeding 50 billion coils , used by two billion people worldwide annually . Despite strong evidence that coils prevent mosquito bites a systematic review concluded that there is no evidence that burning mosquito coils prevents malaria acquisition . Therefore , the current trial was design ed to measure and compare prevention of malaria infection by mosquito coils or long-lasting insecticidal net ( LLIN ) or a combination of the two in Yunnan , China in the Greater Mekong sub-region . Methods A four-arm single blind household-r and omized design was chosen as coils emanate insecticide throughout the household . Households enrolled at baseline were r and omly allocated by the lottery method to one of the four intervention arms : ( i ) nothing , ( ii ) 0.03 % transfluthrin coils alone , ( iii ) deltamethrin long-lasting insecticide treated nets , ( LLINs ) alone or ( iv ) a combination of transfluthrin coils and deltamethrin LLINs . All household members were recruited to the study , with only those households excluded with pregnant or breastfeeding mothers , members with chest complaints or allergies or members that regularly slept away from home . The main outcome of interest was Plasmodium falciparum malaria prevalence detected by rapid diagnostic tests ( RDTs ) during six repeated monthly cross-sectional surveys . The secondary outcome of interest was the effect on Plasmodium vivax prevalence detected in the same way . Results A total of 2,052 households were recruited into the study , comprising 7,341 individuals The odds ratios of testing positive by RDT with P. falciparum or P. vivax were > 75 % lower for all intervention arms compared with the control arm . Coils alone provided 77 % protection ( 95 % CI : 50%-89 % ) , LLINs provided 91 % protection ( 95 % CI : 72%-97 % ) and the combination of coils and LLINs provided 94 % protection ( 95 % CI : 77%-99 % ) against P. falciparum compared with the control arm . There was no statistically significant difference between the protective efficacies of the different interventions . Conclusions This is the first robust clinical evaluation of transfluthrin mosquito coils as a means to reduce malaria and the high degree of infection prevented would indicate they represent a potentially highly effective tool , which could be integrated into larger vector control programmes . Trial registration Clinical Trials.gov Identifier : NCT00442442 , March 2007 BACKGROUND House screening should protect people against malaria . We assessed whether two types of house screening -- full screening of windows , doors , and closing eaves , or installation of screened ceilings -- could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission . METHODS During 2006 and 2007 , 500 occupied houses in and near Farafenni town in The Gambia , an area with low use of insecticide-treated bednets , were r and omly assigned to receive full screening , screened ceilings , or no screening ( control ) . R and omisation was done by computer-generated list , in permuted blocks of five houses in the ratio 2:2:1 . Screening was not treated with insecticide . Exposure to mosquitoes indoors was assessed by fortnightly light trap collection s during the transmission season . Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night . Secondary endpoints included frequency of anaemia ( haemoglobin concentration < 80 g/L ) and parasitaemia at the end of the transmission season in children ( aged 6 months to 10 years ) who were living in the study houses . Analysis was by modified intention to treat ( ITT ) , including all r and omised houses for which there were some outcome data and all children from those houses who were sample d for haemoglobin and parasitaemia . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N51184253 . FINDINGS 462 houses were included in the modified ITT analysis ( full screening , n=188 ; screened ceilings , n=178 ; control , n=96 ) . The mean number of A gambiae caught in houses without screening was 37.5 per trap per night ( 95 % CI 31.6 - 43.3 ) , compared with 15.2 ( 12.9 - 17.4 ) in houses with full screening ( ratio of means 0.41 , 95 % CI 0.31 - 0.54 ; p<0.0001 ) and 19.1 ( 16.1 - 22.1 ) in houses with screened ceilings ( ratio 0.53 , 0.40 - 0.70 ; p<0.0001 ) . 755 children completed the study , of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes . 30 ( 19 % ) of 158 children from control houses had anaemia , compared with 38 ( 12 % ) of 309 from houses with full screening ( adjusted odds ratio [ OR ] 0.53 , 95 % CI 0.29 - 0.97 ; p=0.04 ) , and 31 ( 12 % ) of 264 from houses with screened ceilings ( OR 0.51 , 0.27 - 0.96 ; p=0.04 ) . Frequency of parasitaemia did not differ between intervention and control groups . INTERPRETATION House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children . FUNDING Medical Research Council Background In malaria-endemic areas , residents of modern houses have less malaria than those living in traditional houses . This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets ( LLINs ) and prompt treatment in The Gambia , determine the incremental cost-effectiveness of the interventions , and analyze the housing market in The Gambia . Methods / design A two-armed , household , cluster-r and omized , controlled study will be conducted to assess whether improved housing and LLINs combine to provide better protection against clinical malaria in children than LLINs alone in The Gambia . The unit of r and omization will be the household , defined as a house and its occupants . A total of 800 households will be enrolled and will receive LLINs , and 400 will receive improved housing before clinical follow-up . One child aged 6 months to 13 years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons . Episodes of clinical malaria will be the primary endpoint . Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection , parasite density , and the prevalence of anemia . Exposure to malaria parasites will be assessed using light traps , followed by detection of Anopheles gambiae species and sporozoite infection . Ancillary economic and social science studies will undertake a cost-effectiveness analysis and use qualitative and participatory methods to explore the acceptability of the housing modifications and to design strategies for scaling-up housing interventions . Discussion The study is the first of its kind to measure the efficacy of housing on reducing clinical malaria , assess the incremental cost-effectiveness of improved housing , and identify mechanisms for scaling up housing interventions . Trial findings will help inform policy makers on improved housing for malaria control in sub-Saharan Africa . Trial registration IS RCT N Registry , IS RCT N02622179 . Registered on 23 September 2014 Background In Vietnam , malaria remains a problem in some remote areas located along its international borders and in the central highl and s , partly due to the bionomics of the local vector , mainly found in forested areas and less vulnerable to st and ard control measures . Long Lasting Insecticidal Hammocks ( LLIH ) , a tailored and user-friendly tool for forest workers , may further contribute in reducing the malaria burden . Their effectiveness was tested in a large community-based intervention trial carried out in Ninh Thuan province in Central Vietnam . Methods and Findings Thirty villages ( population 18,646 ) were assembled in 20 clusters ( 1,000 individuals per cluster ) that were r and omly allocated to either the intervention or control group ( no LLIH ) after stratification according to the pre-intervention P. falciparum antibody prevalence ( < 30 % ; ≥30 % ) . LLIH were distributed to the intervention group in December 2004 . For the following 2 years , the incidence of clinical malaria and the prevalence of infection were determined by passive case detection at community level and by bi-annual malariometric surveys . A 2-fold larger effect on malaria incidence in the intervention as compared to the control group was observed . Similarly , malaria prevalence decreased more substantially in the intervention ( 1.6-fold greater reduction ) than in the control group . Both for incidence and prevalence , a stronger and earlier effect of the intervention was observed in the high endemicity stratum . The number of malaria cases and infections averted by the intervention overall was estimated at 10.5 per 1,000 persons and 5.6/100 individuals , respectively , for the last half of 2006 . In the high endemicity stratum , the impact was much higher , i.e. 29/1000 malaria cases and 15.7 infections/100 individuals averted . Conclusions LLIH reduced malaria incidence and prevalence in this remote and forested area of Central Vietnam . As the targets of the newly-launched Global Malaria Action Plan include the 75 % reduction of the global malaria cases by 2015 and eventually the elimination/eradication of malaria in the long term , LLIH may represent an additional tool for reaching such objectives , particularly in high endemicity areas where st and ard control tools have a modest impact , such as in remote and forested areas of Southeast Asia and possibly South America . Trial Registration Clinical Trials.gov Insecticide-treated mosquito nets ( ITN ) provide excellent protection against malaria ; however , they have a number of shortcomings that are particularly evident in politically unstable countries or countries at war : not everyone at risk can necessarily afford a net , nets may be difficult to obtain or import , nets may not be suitable for migrants or refugees sleeping under tents or plastic shelter . There is a need to develop cheaper , locally appropriate alternatives for the most impoverished and for victims of complex emergencies . Afghan women , in common with many Muslim peoples of Asia , wear a veil or wrap known as a chaddar to cover the head and upper body . This cloth doubles as a sheet at night , when they are used by both sexes . A r and omized controlled trial was undertaken in which 10 % of the families of an Afghan refugee camp ( population 3950 ) in north-western Pakistan had their chaddars and top-sheets treated with permethrin insecticide at a dosage of 1 g/m2 while a further 10 % had their chaddars treated with placebo formulation . Malaria episodes were recorded by passive case detection at the camp 's health centre . From August to November the odds of having a falciparum or vivax malaria episode were reduced by 64 % in children aged 0 - 10 years and by 38 % in refugees aged < 20 years in the group using permethrin-treated chaddars and top-sheets . Incidence in refugees over 20 years of age was not significantly reduced . The cost of the permethrin treatment per person protected ( US$ 0.17 ) was similar to that for treating bednets ( and cost only 10 - 20 % of the price of a new bednet ) . An entomological study simulating real-life conditions indicated that host-seeking mosquitoes were up to 70 % less successful at feeding on men sleeping under treated chaddars and some were killed by the insecticide . Permethrin-treated top-sheets and blankets should provide appropriate and effective protection from malaria in complex emergencies . In Islamic and non-Islamic countries in Asia , treated chaddars and top-sheets should offer a satisfactory solution for the most vulnerable who can not afford treated nets BACKGROUND Despite gains in malaria control through impregnated treated nets ( ITN ) , malaria remains a major concern . Netting is expensive and impractical for many communities . Here we present the findings of a community-based trial of impregnated bedsheets ( shukas ) in Kenya . METHODS A total of 472 individuals were enrolled in a r and omized community trial where the unit of r and omization was the hamlet ( manyatta ) . Baseline data included socio-demographic data , parasite prevalence data from thick and thin blood smears , and clinical measures of malaria . The intervention involved the dipping of shukas owned by the experimental group in permethrin . FINDINGS The prevalence of malaria in the study population ( based on laboratory results ) was considerably lower than that used for the power calculation based on clinical estimates ( 2.2 % versus 20 % ) . For those aged 6 or over , the rate of malaria cases ( events per 10 000 person-days at risk ) was 1.41 in the experimental group versus 7.49 in the control group ( incidence rate ratio 0.187 , 95 % CI : 0.046- 0.770 ) . For children < /=5 years of age results were imprecise with no clear benefit of the intervention . CONCLUSIONS These results suggest that permethrin-impregnated bedsheets may be protective against malaria prevention but further studies with greater power are required to confirm this We conducted a community-r and omized controlled trial in an area of moderate malaria transmission in the Amazon region , southern Venezuela , home of the Yanomami indigenous ethnic group . The aim was to compare the malaria incidence rate in villages with lambdacyhalothrin-treated hammock nets ( ITHN ) or with placebo-treated hammock nets ( PTHN ) . In both arms of the study , intensive surveillance for early case detection was maintained and prompt malaria treatment was administered . Baseline data were collected before the intervention and a population of around 924 Yanomami was followed for 2 years . Despite the recent introduction of nets in the Yanomami villages and the adverse natural conditions in the area , the nets were accepted enthusiastically by the study population , used conscientiously and looked after carefully . The malaria incidence rate per thous and person-years at risk was 114.6 in the IHTN group and 186.8 in the PTHN group . The adjusted rate ratios indicated that ITHN prevent 56 % [ IRR : 0.44 , 95 % confidence interval ( CI ) : 52 - 59 % ] of new malaria cases . ITHN reduced the prevalence of parasitaemia by 83 % [ relative risks ( RR ) : 0.17 , 95 % CI : 47 - 100 % ] , according to a cross-sectional survey carried out during the high transmission season . The prevalence of splenomegaly and anaemia was too low to detect any possible reduction as a result of ITHN . The main conclusion of the present study is that ITHN can reduce malaria incidence in the area and it is the most feasible method for malaria control in a forested area where indigenous villages are scattered over a large territory . This is the first community-level epidemiological trial to show that ITHN are highly effective against malaria transmitted by Anopheles darlingi BACKGROUND The st and ard method of malaria control in south Asia , indoor spraying of houses with residual insecticide , is becoming prohibitively expensive to implement and new approaches are needed . Since the region 's vector mosquitoes feed predominantly on domestic animals and only secondarily on human beings , to apply insecticide to surfaces of cattle instead might be more costeffective . We aim ed to investigate whether domestic livestock treated with deltamethrin ( applied by a sponging method ) would prove toxic to mosquitoes and therefore aid in malaria control . METHODS Six Afghan refugee settlements in Pakistan were r and omly assigned to one of two groups . In one group livestock were treated with deltamethrin during the malaria transmission seasons of 1995 and 1997 , whereas in the other group livestock were treated during the 1996 season . Malaria was monitored by passive case detection at village clinics and by cross-sectional surveillance . Mosquitoes were also monitored . FINDINGS According to clinic records the incidence of malaria caused by Plasmodium falciparum decreased by 56 % ( 95 % CI 14 - 78 % ) and P vivax by 31 % ( 5 - 50 % ) in livestock-treated villages . Cross-sectional surveys showed comparable decreases in parasite prevalence . The density and life expectancy of Anopheles stephensi and A culicifacies population s were reduced in treated villages . The efficacy of livestock treatment was similar to that of indoor spraying but campaign costs were 80 % less . When applied in a highly endemic settlement , the incidence of falciparum malaria decreased from 280 episodes per 1000 person-years to nine episodes per 1000 person-years . INTERPRETATIONS Insecticide treatment of livestock is a cost-effective and promising alternative for south Asia and other regions where primary vectors are zoophilic |
11,229 | 20,070,915 | In children , strong evidence of effect was found for multicomponent interventions on fruit and vegetable intakes .
Limited evidence of effect was found for educational interventions on behaviour , and for environmental interventions on fruit and vegetable intakes .
Interventions that specifically targeted children from lower socio-economic status groups showed limited evidence of effect on behaviour .
In adolescents , moderate evidence of effect was found for educational interventions on behaviour and limited evidence of effect for multicomponent programmes on behaviour .
To conclude , evidence was found for the effectiveness of especially multicomponent interventions promoting a healthy diet in school-aged children in European Union countries on self-reported dietary behaviour . | The objective of the present review was to summarise the existing European published and ' grey ' literature on the effectiveness of school-based interventions to promote a healthy diet in children ( 6 - 12 years old ) and adolescents ( 13 - 18 years old ) . | This study reports the effect of the Fruits and Vegetables Make the Marks intervention , a school-based fruit and vegetable intervention consisting of a home economics classroom component and parental involvement and encouraged participation in the Norwegian School Fruit Programme , all delivered during the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 369 pupils ( 69 % ; mean age , 11.3 years at baseline ) participated in all three surveys . No effect of the intervention was found for intake of fruit and vegetables eaten at school or all day , neither at Follow-up 1 nor at Follow-up 2 . On analysing the effects on potential mediators , significant differences between intervention and control groups were found for Awareness of the five-a-day recommendations only . The intervention programme was rated as very good by the teachers , and the pupils reported that they enjoyed it . However , the intervention failed to change fruit and vegetable intake , probably because it did not succeed in changing the pupils ' preferences for or the accessibility of fruit and vegetables -- the two strongest correlates of children 's fruit and vegetable intake Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design OBJECTIVE To measure the effect of a school fruit and vegetable subscription on children 's intake of fruit and vegetables after 5 weeks of intervention . SETTING Seven primary schools in Denmark . DESIGN AND METHODS Intervention schools ( n=4 ) were offered a fruit and vegetable subscription comprising one piece per day . Control schools situated in another municipality were not offered the subscription . Intake of fruit and vegetables was measured at baseline and 5 weeks after the start of the subscription . Two methods were used for dietary assessment : a pre-coded 24-hour recall form including total food intake and a food-frequency question naire ( FFQ ) including only fruit and vegetables . SUBJECTS Children aged 6 - 10 years ( n=804 from intervention schools and n=689 from control schools ) . Response rate in the dietary assessment was 31 % . RESULTS At intervention schools 45 % of the children enrolled in the subscription . After 5 weeks of intervention , both subscribers and non-subscribers had increased their intake of fruit by 0.4 ( P=0.019 ) and 0.3 ( P=0.008 ) pieces per school day , respectively , but no change was observed in vegetable intake . Total intake increased only for non-subscribers by 0.4 piece/school day ( P=0.008 ) mainly due to the consistent increase in fruit intake . No change in intake was measured at control schools . Only the 24-hour recall question naire was sensitive enough to pick up the changes of the subscription , whereas the FFQ was not . CONCLUSION Five weeks with the subscription affected both subscribers and non-subscribers to increase intake of fruit . This may indicate that the subscription had an additional effect of stimulating parents of non-subscribers to supply their children with fruit . The results stress the importance of evaluating the effect of this type of programme , and the carefulness needed in design ing the evaluation study OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake BACKGROUND Secondary school students often do not drink sufficient quantities of water during the school day to prevent dehydration , promote learning and good health . The study aim ed to measure the effect of health promotion and the free provision of cooled filtered water on the consumption of water and soft drinks . It also aim ed to explore students ' views of drinking water provision . METHODS A study was conducted with three secondary schools in North Tyneside . Over a 3 month period one school was given cooled filtered water and active promotion ( W + P ) , another had water only ( W ) . The control school ( C ) took part in post-intervention focus group work . RESULTS The average volume of water drunk by students , in school ' W + P ' was greater ( P = 0.05 ) than that drunk in school ' W ' and control school ' C ' . The volume of soft drinks purchased by students in all three schools before and during the intervention remained static . Focus group data revealed that students viewed their existing water provision as poor and wanted sufficient supplies of cooled filtered water in school . CONCLUSIONS This pilot study indicates that active promotion of water drinking increased consumption of water by secondary school students . Further developments of the project are suggested CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs Background : The positive effects of computer-tailored dietary fat intake interventions have been demonstrated in adults , but few studies have investigated the impact on adolescents . Purpose : The purpose is to evaluate the acceptability , feasibility and effectiveness of a computer-tailored dietary fat intake education program for adolescents . Methods : A r and om sample of 10 schools , 5 with general and 5 with technical-vocational education programs , were selected to participate . In each of the 10 schools , 2 classes of 7th grade rs were r and omly assigned to the intervention ( n=153 ) or control ( no-intervention , n=151 ) condition . Students were exposed once in class to a 50-min theory-based computer-tailored dietary fat intake intervention . Question naires were completed 1 week before ( food frequency question naire for dietary fat intake + psychosocial determinants ) and 3 months after ( process evaluation + food frequency question naire for dietary fat intake + psychosocial determinants ) the intervention . Results : About one in three students evaluated the intervention as interesting ( 34 % ) , novel ( 38 % ) , personally relevant ( 26 % ) , credible ( 34 % ) , and correct ( 38 % ) . Half of the students evaluated the intervention messages to be too long , and one fourth did not read the intervention messages . A decrease in dietary fat consumption was shown in girls enrolled in technical-vocational schools ( F=3.5 , p≤.05 ) and in boys and girls undertaking general education who reported to have read the intervention messages ( F=3.6 , p≤.05 ) ; however , no intervention effects were detected for the total sample . Conclusions : Further improvements to the intervention for use in adolescents should be evaluated . Given that a positive impact was shown in most adolescents and that a computer-tailored dietary fat intake education program has the capability of reaching large groups at low cost , this study shows that using such interventions in adolescents has potential OBJECTIVE To measure the effects of two school-based interventions on children 's intake of fruit and vegetables ( F&V ) . DESIGN AND METHODS A total of six primary schools were r and omly assigned to ( 1 ) a free F&V distribution programme , or ( 2 ) a multicomponent programme , consisting of a classroom curriculum and parental involvement . The two interventions were evaluated on their effects and compared with six control schools in a pre-test-post-test design . Two methods were used for dietary assessment : a pre-structured food recall and a food-frequency question naire including only F&V. SUBJECTS A total of 939 parents of children aged 4 - 12 years filled out the question naire at both pre-test and post-test . The response rate was 54 % . RESULTS Multilevel analyses showed that both programmes were equally effective in increasing children 's fruit consumption by 0.2 portions per day . The free F&V distribution increased vegetable intake among non-native children and the oldest age group , and the multicomponent programme among the oldest children and girls . The distribution also caused an increased 24 h fruit , juice and vegetable intake among the youngest and the oldest age groups , and the multicomponent programme among all children . CONCLUSION The results of this study indicate that both interventions were shown to be effective for different subgroups regarding age , gender and ethnicity . When comparing both interventions , the distribution programme was shown to be more effective , especially in increasing vegetable consumption . An important next step will be to investigate which intervention has the greatest potential to be implemented in primary schools This study reports the effect of a school-r and omized fruit and vegetable intervention consisting of a subscription to the Norwegian School Fruit Programme at no parental cost , and the Fruit and Vegetables Make the Marks ( FVMM ) educational programme , both delivered in the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 517 pupils ( 84 % ; mean age , 11.3 years at baseline ) participated in all three surveys . At both Follow-up 1 and Follow-up 2 , strong intervention effects were observed for all-day fruit and vegetable intake ( effect sizes were 0.6 and 0.5 portions , respectively ) . The sustained effect at Follow-up 2 , 1 year after the end of the intervention , can partly be explained by greater participation rates in the School Fruit Programme ( st and ard paid subscription ) . We conclude that the effects observed are most likely due to the no-cost subscription and not due to the FVMM educational programme , and that providing pupils with a piece of fruit or a vegetable at school at no cost for the parents is an effective strategy to increase school children 's intake of fruit and vegetables . The effect is also sustained 1 year after the end of the no-cost subscription , providing increased health benefits The aim of this study was to examine the fidelity and completeness of the implementation of a school-based healthful diet promotion programme called ' Krachtvoer ' ( we use the Dutch title of the programme throughout this article . A possible translation is Power Food , but this does not reflect the play on words in the Dutch title ) , aim ed at lower vocational training students aged 12 - 14 years . The teachers ' and students ' opinions of the programme were also assessed , as well as the association between these opinions and the level of implementation . Data were collected through structured teachers ' monitoring reports , in-class observations and in-depth interviews with teachers . Further data were drawn from a student question naire included in a concurrent cluster-r and omized baseline post-test experimental study evaluating the effects of the programme . The present study indicates that the teachers implemented the programme largely according to plan , that the teachers appreciated most parts of the programme and that the students who were exposed to the programme were more appreciative of their nutrition education lessons than students who followed the usual curriculum . However , programme elements that teachers did not like were often not implemented . We conclude that the Krachtvoer programme is a promising tool to encourage students in lower vocational training to adopt diets that are more healthful . The present study revealed the stronger and weaker parts of the programme and can thus guide programme improvement OBJECTIVE Children 's fruit/vegetable intake is still below recommended levels . This study applied Internet-tailored advice for schoolchildren and Internet-supported brief dietary counselling ( with child and parent ) within preventive health care to promote fruit/vegetable intake . SETTING /SUBJECTS The study involved 30 seventh- grade classes ( 16 in the intervention group and 14 in the control group ) with a total of 675 children aged 9 - 12 years , of whom 495 were allowed to participate . DESIGN A cluster-r and omised baseline-post-test experimental design was applied . During school hours , all children completed Internet-administered question naires on fruit/vegetable intake and related determinants . Children in the intervention group received immediate online individually tailored nutrition feedback . For each child in the intervention group , a nurse received information concerning the assessment of fruit/vegetable intake via the Internet to support a 5 min counselling protocol to promote fruit/vegetable intake . Children completed a similar post-test question naire 3 months after the first assessment . Intention-to-treat analyses were conducted using multilevel regression analyses . RESULTS A total of 486 children ( 98 % of 495 ) participated ( 263 in the intervention group , 223 in the control group ) ; 240 child-parent couples in the intervention group attended the counselling . Awareness of inadequate fruit intake ( odds ratio ( OR ) = 3.0 ; 95 % confidence interval ( CI ) = 1.8 - 5.3 ) and knowledge of recommended vegetable intake levels ( OR = 2.7 ; 95 % CI = 1.8 - 4.1 ) were significantly more likely at post-test in the intervention group than in the control group . No significant effects were found on intake or other determinants . CONCLUSIONS A compact , integrated two-component intervention can induce positive changes in knowledge and awareness of intake levels of fruit/vegetables among schoolchildren . To induce changes in intake levels , more comprehensive interventions may be needed OBJECTIVE The aim of this study was to assess the behavioural effects of a school-based healthful diet promotion intervention implemented in lower vocational schools . DESIGN A cluster-r and omised pre-test-post-test experimental design was used , and data were collected by means of written question naires . SETTING Students of 18 Dutch lower vocational schools . SUBJECTS The final sample consisted of 10 experimental schools with 13 teachers , 37 classes and 879 students , and eight control schools with 10 teachers , 31 classes and 734 students ( total n = 1613 ) . RESULTS Fixed regression analyses revealed beneficial effects on the behavioural measures relating to fruit intake ( as assessed by a food frequency measure and fruit consumption during the previous day ) , and most behavioural measures related to high-fat snack intake ( food frequency measure , and number of snacks and total fat intake from snacks during the previous day ) . The behavioural effects relating to breakfast habits were limited . Some positive behavioural effects occurred in the total target population , others mainly or only among students with more unfavourable intakes at baseline . Mixed regression analysis found comparable regression coefficients for the behavioural outcomes , but the effects related to fruit intake were no longer statistically significant . CONCLUSIONS Although we did not find the expected effects on all outcome indicators , the total pattern of results suggest that Krachtvoer offered a surplus value over existing curricula . However , some programme elements need to be revised to improve effectiveness and prevent negative effects , and more information is needed about the long-term effects of the programme The purpose was to investigate the degree of implementation and appreciation of a comprehensive school-r and omized fruit and vegetable intervention program and to what extent these factors were associated with changes in reported fruit and vegetable intake . The study was conducted among 10- to 13-year old children exposed to the intervention during the school year 2003 - 04 in Norway , Spain and the Netherl and s. Children , parents and teachers completed question naires regarding ( i ) the implementation of the school curriculum , ( ii ) parental involvement , ( iii ) distribution of fruit and vegetables at school , ( iv ) children 's appreciation of the project and ( v ) children 's intake levels . Univariate analyses of covariance and multilevel multivariate regression analyses indicated that teacher-reported level of implementation of the school curriculum and schoolchildren 's appreciation of the project were important determinants of changes in intake . The results point to the importance of optimal implementation of an attractive school curriculum Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years STUDY OBJECTIVE To describe the economics of UK school breakfast clubs , to estimate costs result ing from clubs and to investigate relationships between costs and outcomes . DESIGN A postal survey of schools with a 1-year follow-up , a cluster r and omized controlled trial , case studies , semi-structured interviews with parents and a secondary econometric analysis . SETTING Engl and , the UK . MAIN RESULTS Key economic differences were identified between clubs based in primary schools and those based in secondary schools in terms of both funding levels and cost structures . However , funding levels were not a significant determinant of the observed outcomes in either type of school . CONCLUSIONS For formal economic evaluation to succeed during implementation of a new initiative , a clearer underst and ing of relevant outcomes and the distinction between short- and long-term outcomes and potential individual , institutional and societal benefits are required from an early stage This study values the effectiveness of nutrition education interventions carried out by teachers with active didactic method ologies . The research was carried out by administering a frequency of food intake question naire , before and after the intervention . To compare the answers given before and after the educational intervention the Wilcoxon-test was applied to dependent data . Our research confirmed that a substantial percentage of children do not show a correct nutrition and therefore nutrition education interventions are opportune and necessary . In the group with " insufficient execution " particular variations are not taken place . In the group with " sufficient execution " increase the number of subjects having breakfast , particularly with milk and biscuits , and decrease the snakes intake . Moreover there is a general decrease of intake food as meat , fish , vegetables , salami and legumes . So this educational intervention seems to have only partial effectiveness OBJECTIVE This study compared a motivational intervention based on the Theory of Planned Behaviour ( TPB ) with a volitional intervention based on implementation intentions . DESIGN The study employed a quantitative longitudinal question naire design involving two waves of data collection . METHOD Participants ( N=198 ) were r and omly allocated to a control group or one of two intervention groups . TPB variables , and fruit and vegetable consumption were assessed at the beginning of the study ( time 1 ) and 2 weeks later ( time 2 ) . Experimental group A formed an implementation intention , about how , when and where they could eat five portions a day , whilst experimental group B stated ways they could overcome motivational barriers to eating five portions a day . RESULTS Both interventions were found to increase fruit and vegetable consumption significantly , although only the volitional intervention demonstrated a significant increase in fruit and vegetable consumption over the control intervention . CONCLUSIONS The present study found support for two interventions in increasing fruit and vegetable consumption in children . These findings are encouraging regarding the use of these types of interventions within schools to improve children 's eating behaviour STUDY OBJECTIVE To measure the health , educational and social impacts of breakfast club provision in schools serving deprived areas across Engl and . DESIGN A cluster r and omized controlled trial and an observational analysis . SETTING Engl and , the UK . INTERVENTION funding to establish a school-based breakfast club vs. control ( no funding ) . MAIN RESULTS Intention to treat analysis showed improved concentration ( Trail Making Test Part A ) amongst the intervention group at 3 months . Fewer pupils within the intervention group reported having skipped classes within the last month and fewer pupils within the intervention group reported having skipped 1 or more days of school within the last month at 1 year . Observational analysis at 1 year showed a higher proportion of primary -aged breakfast club attendees reported eating fruit for breakfast in comparison to non-attendees . A higher proportion of breakfast club attendees had borderline or abnormal conduct and total difficulties scores ( primary -aged pupils ) and prosocial score ( secondary -aged pupils ) . CONCLUSIONS Analyses revealed a mixed picture of benefit and apparent disbenefit . This study illustrated the challenges of evaluating a complex intervention in which the evaluators had less control than is usual in r and omized trials over recruitment , eligibility checking and implementation . If the impact of new policy initiatives is to be assessed using the most robust forms of evaluation , social policy needs to be organized so that evaluations can be constructed as experiments . This is likely to prove most difficult where the perceived value of implementing an intervention rapidly is high This paper examines how the concept of the ' evidence -based ' approach has transferred from clinical medicine to public health and has been applied to health promotion and policy making . In policy making evidence has always been interpreted broadly to cover all types of reasoned enquiry and after some debate the same is now true for health promotion . Taking communities rather than individuals as the unit of intervention and the importance of context means that frequently r and omized controlled trials are not appropriate for study of public health interventions . Further , the notion of a ' best solution ' ignores the complexity of the decision making process . Evidence ' enlightens ' policy makers shaping how policy problems are framed rather than providing the answer to any particular problem . There are lessons from the way that evidence -based policy is being applied in public health that could usefully be taken back into medicine OBJECTIVE We evaluated in a prospect i ve study microcomputer nutritional teaching games and their contribution to the children 's acquisition of nutritional knowledge and improvement of eating habits . MATERIAL AND METHODS One thous and eight hundred seventy-six children aged 7 - 12 years took part in this study at school . All 16 schools of the same school district were r and omized into two groups : games group and control group , both receiving conventional nutritional teaching by their teachers . The children in the games group played computer games during the conventional nutritional teaching period ( 2 hours a week for 5 weeks ) . At completion of the study , dietetic knowledge and dietary records were evaluated in both groups . RESULTS Dietary knowledge tests results were better in the games group ( p<0.001 ) . The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories : more carbohydrate ( 46.4 + /- 0.2 % vs 45.7 + /- 0.2 % , p<0.05 ) , less fat ( 37.1 + /- 0.1 % vs 37.6 + /- 0.2 % , p<0.05 ) , less protein ( 16.5 + /- 0.1 % vs 16.7 + /- 0.1 % , p<0.05 ) , less saccharose ( 11.5 + /- 0.1 % vs 12.2 + /- 0.2 % , p<0.001 ) , more calcium ( p<0.001 ) and more fiber ( p<0.05 ) . The games group had a better snack at 10 a.m. , a less copious lunch and less nibbling ( p<0.001 ) . CONCLUSION The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group . Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching Objective : Evaluation of the impact on diet of the school fruit and vegetable scheme ( SFVS ) . Design : Non-r and omised controlled trial . Setting : Infant and primary schools in the north of Engl and . Participants : 3703 children aged four to six years ( reception , year 1 , and year 2 ) . Intervention : One portion of fruit or vegetable provided per child on each school day between February and December 2004 . Main outcome measures : Fruit and vegetables consumed and intake of nutrients . Results : The SFVS was associated with an increase in fruit intake across reception and year 1 pupils of 0.4 portions ( 95 % confidence interval , 0.2 to 0.5 ) and 0.6 portions ( 0.4 to 0.9 ) , respectively , at three months , which fell to 0.2 ( 0.1 to 0.4 ) and 0.3 ( 0.1 to 0.6 ) at seven months . In year 2 it was associated with an increase of 0.5 portions ( 0.2 to 0.7 ) of fruit at three months , which fell to baseline values at seven months when these children were no longer eligible for the scheme . Overall , at seven months there were no changes in vegetable consumption , no associations between the SFVS and energy , fat , or salt intake , and small changes in carotene and vitamin C intake . Conclusions : The SFVS promoted an increase in fruit intake after three months . At seven months the effect remained significant but reduced , and it returned to baseline in year 2 when pupils were no longer part of the scheme . There was a small impact on the intake of some nutrients across the children surveyed The objective of the present study was to evaluate the effects of the Pro Children intervention on schoolchildren 's fruit and vegetable ( FV ) intake after 1 and 2 years of follow-up . The intervention combined a FV curriculum with efforts to improve FV availability at schools and at home . Effects were examined in a group-r and omised trial among 1,472 10 - 11-year-old children from sixty-two schools in Norway , the Netherl and s and Spain . FV intake was assessed by means of vali date d self-administered question naires completed before the intervention ( September 2003 ) , immediately after the first year of the intervention ( May 2004 ) and 1 year later ( May 2005 ) . Data were analysed using multilevel linear regression analyses with age and sex as covariates . Significant intervention effects for FV intake were found at first follow-up in the total sample . The adjusted FV intake reported by the children from intervention schools was 20 % higher than FV intake reported by children from control schools . At 1 year later , a significant impact was only observed in Norway . Positive intervention effects on FV intake occurred both at school and outside school . We conclude that the Pro Children intervention is a promising means to promote European schoolchildren 's FV intakes , but mainly fruit intake , in the short term . As shown in Norway , where the intervention was best implemented , the intervention might also result in longer-term effects . Further strategies need to be developed that can improve implementation , have an impact on vegetable intake and can secure sustained effects The objective of the study was to test the effectiveness of an intervention program based on the theoretical framework of the Theory of Planned Behavior , with the addition of attitude strength and role identity . The aim was to alter adolescents ' healthy eating attitudes and behaviour . In the sample were 335 high school students , who were divided into intervention and control groups . The intervention lasted 12 weeks and included posters and lectures promoting healthy eating . The measures included a question naire assessing the hypothesis and a food frequency question naire which measured eating habits . Analysis showed the intervention was effective in improving attitudes toward healthy eating and attitude strength , intention , perceived behavioral control , and healthy eating behaviour , but not effective in predicting subjective norms and role identity . Results provide evidence that intervention changed attitudes toward a behavior in a school setting BACKGROUND This study reports the effect of providing Norwegian school children with free fruit or vegetables every school day and the effect of an existing fee-based School Fruit Programme . METHODS Seventh grade pupils and their parents completed question naires at baseline ( autumn 2001 ) and at follow-up ( spring 2002 ) . Nine schools participated in the School Fruit Programme for free ( Free fruit ) , nine schools took part at st and ard conditions ( Paid fruit ) , and 20 schools did not take part in the subscription programme ( No fruit ) . A total of 795 7th grade rs ( 11 or 12 years old at baseline ) participated both at baseline and at follow-up . RESULTS At follow-up , pupils attending the Free fruit schools had significantly higher intake of fruit and vegetables at school than the pupils at the Paid fruit and No fruit schools ( P < 0.001 , mean intakes were 1.1 , 0.4 and 0.2 portions , respectively ) . Subscribers at the Paid fruit schools had significantly higher intake than the non-subscribers at the same schools . CONCLUSIONS Providing a free piece of fruit or a vegetable is an effective strategy to increase school children 's fruit and vegetable intake . The existing School Fruit Programme appears to increase the intake among the subscribers , but thereby also tends to increase an existing difference in consumption patterns among subscribers and non-subscribers |
11,230 | 21,087,067 | In summary , there is some weak evidence to suggest that several botanical extracts may be effective in reducing the appearance of skin aging but no evidence that this effect is enduring . | Although topical creams and other anti-aging products purport to reduce the appearance of aging and skin wrinkling , there has been no critical analysis in the scientific literature of their effectiveness .
This systematic review critically evaluates the evidence for the effectiveness or efficacy of botanical treatments in reducing skin aging and wrinkling . | BACKGROUND Green tea polyphenols ( GTPs ) have significant antioxidant and antiinflammatory activities , and prior short‐term studies suggest that these compounds may improve photoaging skin . OBJECTIVES To evaluate the long‐term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin . MATERIAL S AND METHODS Double‐blind , placebo‐controlled trial of 56 women aged 25 to 75 r and omized to 250 mg GTPs or placebo twice daily for 2 years . A blinded dermatologist scored the appearance of photodamaged facial skin at 0 , 6 , 12 , and 24 months . A blinded dermatopathologist scored the histologic characteristics of sun‐exposed arm skin at 0 and 24 months . RESULTS Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months ( p=.02 ) and significant improvement in erythema and telangiectasias at 12 months ( p=.02 ) . The placebo group did not have significant improvements in these parameters at 6 months or 12 months . There were no statistically significant differences in other photoaging parameters at 6 , 12 , or 24 months in the GTP or placebo groups . Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months . CONCLUSIONS Long‐term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use . Funding and material s for this study were provided by Nu Skin , Provo , Utah . Dale Kern is an employee of Nu Skin International To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results A double-blind , placebo-controlled trial was conducted to clinical ly evaluate the effect of soy isoflavone aglycone on the aged skin of middle-aged women . Twenty-six women volunteers in their late 30s and early 40s were r and omly assigned to receive either a test food ( 13 women , the test food group ) or a placebo food ( 13 women , the control group ) . These groups were given the test food ( 40 mg of soy isoflavone aglycone per day ) and placebo , respectively , for 12 wk . The extent of linear and fine wrinkles at the lateral angle of the eyes was selected as the major evaluation criterion to assess the effects of foods , and the wrinkles ' area ratio was used as the evaluation parameter . The extent of skin microrelief at the lateral angle of eyes and that of malar skin elasticity were used as secondary evaluation criteria , and the skin microrelief 's area ratio and recovery of skin elasticity were used as the respective evaluation parameters . These parameters were assessed 4 , 8 , and 12 wk after the start of the test food or placebo intake . The test food group showed a statistically significant improvement of fine wrinkles at week 12 ( p<0.05 ) and of malar skin elasticity at week 8 ( p<0.05 ) , compared with the control group . Although there was no significant difference between the test food group and the control group regarding effects on skin microrelief at lateral angle of the eyes , a significant intragroup improvement was observed at week 8 in the test food group ( p<0.05 ) . As for the test food safety , none of the subjects presented adverse symptoms during the study period or discontinued the intake of the test food . These data indicate that the oral intake of 40 mg soy isoflavone aglycones per day improves the aged skin of middle-aged women This study evaluates the efficacy and tolerability of an investigational study cream composed of 3 ingredients ( green and white teas , mangosteen , and pomegranate extract ) , Vitaphenol Skin Cream ( La Jolla Spa MD , La Jolla CA ) , as compared to a placebo cream in rejuvenating facial skin . Twenty healthy females between the ages of 35 and 65 with demonstrable facial wrinkling , achieving a Rao-Goldman wrinkle scale score of 2 or above , applied either Vitaphenol Skin Cream or placebo cream to a r and omized half of their face twice daily for 60 days and returned for follow-up after 2 weeks . Twice as many subjects indicated an enhancement of skin texture ( eg , reduction in pore size , roughness , and touch ) with the usage of Vitaphenol versus placebo . In all , 41 % of the study subjects preferred the half of their face that had been receiving Vitaphenol , while only 0.06 % of the subjects favored the placebo side . PRIMOS images from periorbital skin treated with Vitaphenol demonstrated an average improvement in skin smoothness of 1 mm3 , whereas skin treated with placebo showed an average decrease in smoothness or an increase in skin roughness of 0.9 mm3 . The addition of 3 antioxidants , green and white teas , mangosteen , and pomegranate , have an additive effect to enhance the improvement of age-related changes in the skin BACKGROUND Green tea extracts have gained popularity as ingredients in topical skin care preparations to treat aging skin . Green tea polyphenolic compounds have significant antioxidant and anti-inflammatory activities , and studies suggest that these extracts help mediate ultraviolet radiation damage . OBJECTIVE To evaluate the effects of a combination regimen of topical and oral green tea supplementation on the clinical and histologic characteristics of photoaging . METHODS Forty women with moderate photoaging were r and omized to either a combination regimen of 10 % green tea cream and 300 mg twice-daily green tea oral supplementation or a placebo regimen for 8 weeks . RESULTS No significant differences in clinical grading were found between the green tea-treated and placebo groups , other than higher subjective scores of irritation in the green tea-treated group . Histologic grading of skin biopsies did show significant improvement in the elastic tissue content of treated specimens ( p<.05 ) . CONCLUSION Participants treated with a combination regimen of topical and oral green tea showed histologic improvement in elastic tissue content . Green tea polyphenols have been postulated to protect human skin from the cutaneous signs of photoaging , but clinical ly significant changes could not be detected . Longer supplementation may be required for clinical ly observable improvements Hormones play a central role in skin appearance and are implicated in skin aging . Recently , along with the remarkable increase in interest in natural products , the application of phytohormones in antiaging products has become very important . In this context , we developed date palm kernel extract . Date palm kernel is rich in phytohormones and we investigated the antiaging properties of date palm kernel in this in vivo study on wrinkles . Ten healthy women volunteers , between the ages of 46 and 58 years , applied the cream formula with 5 % date palm kernel or placebo on the eye area twice a day for 5 weeks . The evaluation was made both clinical ly and by silicon replica analysis followed by statistical analysis using the Wilcoxon test . Silicon replica results showed that topical application of date palm kernel reduced the total surface of wrinkles by 27.6 % ( p = 0.038 ) . Moreover , date palm kernel reduced the depth of wrinkles by 3.52 % ( p = 0.0231 ) . These results are statistically significant and were clinical ly confirmed where visual improvement was seen in 60 % of the volunteers treated . This in vivo study demonstrates that date palm kernel exhibits a significant antiwrinkle effect and is therefore of interest in antiaging skin care products Recently , it has become indispensable for anti-aging active ingredients to provide a visible and immediate smoothing antiwrinkle effect . In Quercus suber , suberin is the most important structural component of cork cell walls . Studies have shown that suberin is made up mostly of hydroxycarboxylic acids and that it is endowed with many special mechanical and chemical properties that evoke a possible smoothing effect on the surface of the skin . Therefore , we were interested in investigating the effect of this cork extract on the skin 's surface in a double-blind clinical study . The study was conducted in 15 healthy volunteers , aged 22 to 52 years . The volunteers applied a gel formula with 3 % of cork extract , or placebo gel , on each forearm . Skin surface roughness was evaluated visually by pictures and by silicone replicas 1 and 2 h after application , followed by statistical analysis using the matched-pairs McNemar statistical test . McNemar analysis of the pictures revealed that application of cork extract on the skin result ed in a highly significant reduction of roughness 1 h after application . This effect was observed in 73.3 % of volunteers . Two hours after cork extract application , a highly significant improvement of skin roughness was found in 78.6 % of volunteers . Moreover , silicone replica treatment confirmed significant improvement in average of roughness at 2 h. These results demonstrate that cork extract provides a remarkable and highly significant tensor and smoothing effect on the skin , which could be of great use in anti-aging skin care products R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly |
11,231 | 23,740,608 | For the outcomes discontinuation for adverse events and virologic failures , the RRs were not significant , albeit being not far from the alpha level of 0.05 , thus suggesting a weak evidence of lower incidence of side effects and an higher incidence of virologic failure in the 3NRTI group compared to controls .
The strategy of switching to triple nucleoside regimens shows weak evidence of lower incidence of side effects and a higher incidence of virologic failure in the 3NRTI group compared to controls .
Simplification with 3NRTI holds the advantages of preserving other classes of antiretroviral drugs , to lower blood lipids , and to be cost effective and simple to administer . | BACKGROUND Regimen simplification can be defined as a change in established effective therapy to reduce pill burden and dosing frequency , to enhance tolerability , or to decrease specific food and fluid requirements .
Many patients on suppressive antiretroviral therapy may be considered c and i date s for a simplification strategy and , among them , those who have achieved virologic suppression .
Several clinical trials have evaluated the efficacy of triple nucleoside combination as a simplification therapy in patients who achieved virologic suppression OBJECTIVES The aim of this review is to combine r and omised , controlled trials to examine whether in patients with undetectable viraemia on a Protease inhibitor ( PI ) based regimen simplification treatment with abacavir (ABC)-based triple-nucleoside combinations has similar rates of efficacy and tolerability compared with a PI regimen or simplification with a NNRTIs ( efavirenz-EFV- or nevirapine-NVP ) containing regimen . | CONTEXT Abacavir , a nucleoside analogue , has demonstrated suppression of human immunodeficiency virus ( HIV ) replication alone and in combination therapy . However , the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a st and ard protease inhibitor-containing regimen for initial antiretroviral treatment . OBJECTIVE To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen . DESIGN AND SETTING A multicenter , phase 3 , r and omized , double-blind trial with an enrollment period from August 1997 to June 1998 , with follow-up through 48 weeks at 73 clinical research units in the United States , Canada , Australia , and Europe . PATIENTS Five hundred sixty-two antiretroviral-naive , HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS Patients were stratified by baseline HIV RNA level and r and omly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo . After 16 weeks , patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving r and omized treatment or receive open-label therapy . MAIN OUTCOME MEASURE Virologic suppression , defined as HIV RNA concentration of 400 copies/mL or less at week 48 . RESULTS The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group ( 51 % [ 133/262 ] ) and in the indinavir group ( 51 % [ 136/265 ] ) with a treatment difference of -0.6 % ( 95 % confidence interval [ CI ] , -9 % to 8 % ) . In patients with baseline HIV RNA levels greater than 100 000 copies/mL , the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45 % ( 45/100 ) vs 31 % ( 30/96 ) and a treatment diference of -14 % ( 95 % CI , -27 % to 0 % ) . The 2 treatments were comparable with respect to their effects on CD4 cell count . There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities . One death in the abacavir group was attributed to hypersensitivity reaction , which occurred following rechallenge with abacavir , approximately 3 weeks after initiating study treatment . CONCLUSIONS In this study of antiretroviral-naive HIV-infected adults , the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks Patients with sustained virological suppression on protease inhibitor (PI)-based therapy were r and omly assigned to switch the PI to nevirapine ( n = 155 ) , efavirenz ( n = 156 ) , or abacavir ( n = 149 ) and were followed for at least 3 years regardless of the discontinuation of assigned therapy . There was a higher probability of maintaining virological suppression after 3 years of follow-up with nevirapine or efavirenz than with abacavir . In contrast , abacavir showed a lower incidence of adverse effects leading to drug discontinuation BACKGROUND Evidence from r and omized controlled trials supports the use of triple therapy . Research is required on the effectiveness of quadruple therapy in comparison to this and the relative effectiveness of specific highly active antiretroviral therapy ( HAART ) combinations . METHODS Antiretroviral-naive individuals ( n = 53 ) with an HIV-1 viral load > 100 000 copies/mL were r and omized to receive three-drug HAART with zidovudine/lamivudine ( Combivir ) and efavirenz or quadruple therapy with zidovudine/lamivudine/abacavir ( Trizivir ) and efavirenz ( quad regimen ) . Patients continued on HAART for 48 weeks with regular clinical and immunological assessment . St and ard and ultrasensitive ( < 5 copies/mL ) viral load testing was carried out . RESULTS A DAVG ( difference in averages ) analysis of the fall in viral load and increase in CD4 count showed no significant differences between regimens . Triple therapy result ed in a -4.17 log change ( 95 % CI , -4.48 to -3.85 ) and quadruple therapy in a -4.36 log change ( 95 % CI , -4.68 to -4.03 ) in viral load . For CD4 counts , the triple therapy arm increased by 164 cells/mm(3 ) ( 95 % CI 112 - 217 ) and the quadruple arm by 185 ( 95 % CI , 133 - 237 ) . In an intent-to-treat analysis , 77 % of patients in the triple therapy group reached an undetectable viral load ( < 50 copies/mL ) compared with 84.2 % of the quadruple therapy group . For ultrasensitive viral load testing , 23 % and 18 % of each group , respectively , reached undetectable viral loads . The hazard ratio for attaining a viral load of < 5 copies/mL was 0.59 ( 95 % CI , 0.26 - 1.33 ) for quadruple versus triple therapy . Three individuals in the triple therapy arm and nine in the quadruple therapy arm discontinued treatment . CONCLUSIONS No differences in any analyses were observed between a st and ard of care regimen ( zidovudine/lamivudine and efavirenz ) and the quad regimen ( zidovudine/lamivudine/abacavir and efavirenz ) Background : The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with re introduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression . However , it is still uncertain if this experimental strategy can maintain suppression in the long term . Methods : Patients entered this noninferiority trial ( upper limit 95 % confidence interval : + 12 % ) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir , with HIV RNA < 50 copies per milliliter for more than 6 months . Primary end point was percent of patients without therapeutic failure , defined as confirmed HIV RNA > 500 copies per milliliter with exclusion of monotherapy patients who resuppressed to < 50 copies per milliliter after resuming baseline nucleosides , or loss to follow-up , or change of r and omized therapy other than reinduction . Results : Through 96 weeks , percentage of patient without therapeutic failure was 87 % ( monotherapy , n = 100 ) vs. 78 % ( triple therapy , n = 98 ; 95 % confidence interval : −20 % to + 1.2 % ) . Percentage with HIV RNA < 50 copies per milliliter ( intention to treat , missing = failure , reinduction = failure ) : 77 % ( monotherapy ) vs. 78 % ( triple therapy ) . Low-level viral rebound was more frequent in the monotherapy group . Twelve patients in the monotherapy group ( 12 % ) needed reinduction with nucleosides . Discontinuations due to adverse events were significantly more frequent in the triple therapy group ( 8 % ) than in the monotherapy group ( 0 % ) ; P = 0.003 . Conclusions : At 96-week lopinavir/ritonavir monotherapy with re introduction of nucleosides as needed was noninferior to continuation of triple therapy . Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy . ( Clinical Trials.gov number , NCT00114933 ) Background : The NEFA Study was a r and omized study comparing nevirapine ( NVP ) , efavirenz ( EFV ) or abacavir ( ABC ) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors . Objective : To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms . Methods : Patients with virological failure , defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml , were analysed for phenotypic susceptibility and HIV-1 mutations . Results : Of the 460 patients included in the study , 51 ( 11 % ) experienced virological failure after 24 months of follow-up while on assigned study medication . A higher proportion of patients in the ABC [ 25 ( 17 % ) ] than in the NVP [ 14 ( 9 % ) ] or EFV [ 12 ( 8 % ) ] arms selected resistance to the study drug ( P = 0.04 ) . Moreover , a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms . In general , there was a good concordance among genotype and phenotype resistance testing , except for ABC , stavudine and didanosine , where phenotypic resistance testing added valuable information ( fold change in the median inhibitory concentration ) . Conclusions : Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy . Phenotypic resistance testing may be helpful in interpreting unclear genotypic results BACKGROUND Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele . This study was design ed to establish the effectiveness of prospect i ve HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir . METHODS This double-blind , prospect i ve , r and omized study involved 1956 patients from 19 countries , who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir . We r and omly assigned patients to undergo prospect i ve HLA-B*5701 screening , with exclusion of HLA-B*5701-positive patients from abacavir treatment ( prospect ive-screening group ) , or to undergo a st and ard-of-care approach of abacavir use without prospect i ve HLA-B*5701 screening ( control group ) . All patients who started abacavir were observed for 6 weeks . To immunologically confirm , and enhance the specificity of , the clinical diagnosis of hypersensitivity reaction to abacavir , we performed epicutaneous patch testing with the use of abacavir . RESULTS The prevalence of HLA-B*5701 was 5.6 % ( 109 of 1956 patients ) . Of the patients receiving abacavir , 72 % were men , 84 % were white , and 18 % had not previously received antiretroviral therapy . Screening eliminated immunologically confirmed hypersensitivity reaction ( 0 % in the prospect ive-screening group vs. 2.7 % in the control group , P<0.001 ) , with a negative predictive value of 100 % and a positive predictive value of 47.9 % . Hypersensitivity reaction was clinical ly diagnosed in 93 patients , with a significantly lower incidence in the prospect ive-screening group ( 3.4 % ) than in the control group ( 7.8 % ) ( P<0.001 ) . CONCLUSIONS HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir . In predominantly white population s , similar to the one in this study , 94 % of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir . Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug . ( Clinical Trials.gov number , NCT00340080 . Background : Darunavir/ritonavir ( darunavir/r ) maintenance strategy , in patients with suppressed HIV RNA viremia , is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs . Methods : MONOtherapy Inhibitor protease is a prospect i ve , open-label , noninferiority , 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were r and omized to a darunavir/r triple drug regimen or darunavir/r monotherapy . The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48 ; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml ( time to loss of virologic response ) or any change in treatment . The trial had 80 % power to show noninferiority for the monotherapy arm ( δ=−10 % , 90 % confidence interval ) . Results : A total of 242 patients were screened , 225 of whom were r and omized . In the per protocol efficacy analysis , treatment success was 99 % on darunavir/r triple drug versus 94 % on darunavir/r monotherapy ( δ = −4.9 % , 90 % confidence interval , from −9.1 to −0.8 ) . Similar results were found in intent-to-treat population ( 92 versus 87.5 % , δ = −4.5 % , 90 % confidence interval from −11.2 to 2.1 ) . Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug . No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml . The two groups did not differ in the number of serious adverse events . Conclusion : Darunavir/r monotherapy exhibited efficacy rate over 85 % with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses , but discordant conclusions with respect to the noninferiority margin . Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options Background Hyperlipidemia secondary to protease inhibitors ( PI ) may abate by switching to anti-HIV medications without lipid effects . Method An open-label , r and omized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia ( fasting serum total cholesterol > 200 mg/dL ) who were r and omized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily ( n = 52 ) or a regimen in which their PI was continued ( n = 52 ) for 28 weeks . All patients had undetectable viral loads ( HIV-1 RNA < 50 copies/mL ) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors . Results At baseline , the mean total cholesterol was 243 mg/dL , low density lipoprotein (LDL)-cholesterol 149 mg/dL , high density lipoprotein (HDL)-cholesterol 41 mg/dL , and triglycerides 310 mg/dL. Mean CD4 + cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms , respectively . At week 28 , the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol ( -42 vs -10 mg/dL , P < 0.001 ) , LDL-cholesterol ( -14 vs + 5 mg/dL , P = 0.016 ) , and triglycerides ( -134 vs -36 mg/dL , P = 0.019 ) than the PI-continuation arm , with no differences in HDL-cholesterol ( + 0.2 vs + 1.3 mg/dL , P = 0.583 ) . A higher proportion of patients in the abacavir-switch arm had decreases in protocol -defined total cholesterol and triglyceride toxicity grade s , whereas a smaller proportion had increases in these toxicity grade s. At week 28 , an intent-to treat : missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA < 400 or < 50 copies/mL or adjusted mean change from baseline in CD4 + cell count . Two possible abacavir-related hypersensitivity reactions were reported . No significant changes in glucose , insulin , insulin resistance , C-peptide , or waist-to-hip ratios were observed in either treatment arm , nor were differences in these parameters noted between treatments . Conclusion In hyperlipidemic , antiretroviral-experienced patients with HIV-1 RNA levels < 50 copies/mL and CD4 + cell counts > 500 cells/mm3 , substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period , and it simplifies treatment BACKGROUND Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infa rct ion ( MI ) , possibly related to issues that may bias estimation of treatment effects , such as time-varying confounders , informative dropout , and cohort loss due to competing events . METHODS We analyzed data from 5056 individuals initiating r and omized antiretroviral treatment ( ART ) in AIDS Clinical Trials Group studies ; 1704 started abacavir therapy . An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio ( HR ) of MIs after initiation of a regimen with or without abacavir . RESULTS Through 6 years after ART initiation , 36 MI events were observed in 17,404 person-years of follow-up . No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen ( over a 1-year period : P=.50 ; HR , 0.7 [ 95 % confidence interval { CI } , 0.2 - 2.4 ] ) ; over a 6-year period : P=.24 ; HR , 0.6 [ 95 % CI , 0.3 - 1.4 ] ) ; these results were robust over as-treated and sensitivity analyses . Although the risk of MI decreased over time , there was no evidence to suggest a time-dependent abacavir effect . Classic cardiovascular disease ( CVD ) risk factors were the strongest predictors of MI . CONCLUSION We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk . Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection OBJECTIVES Long-term results at week 96 are needed to evaluate the capacity of the darunavir/ritonavir monotherapy strategy to maintain a sustained control of the HIV-1 viral load . METHODS MONOI is a prospect i ve , open-label , non-inferiority , r and omized , 96 week trial comparing darunavir/ritonavir monotherapy versus a darunavir/ritonavir triple-therapy strategy to maintain HIV-1 viral load suppression in HIV-1-infected patients . CLINICAL TRIAL REGISTRATION NCT00412551 . RESULTS From 225 r and omized patients , 219 patients reached the 48 week follow-up and 211 reached the 96 week follow-up ( 106 patients in the darunavir monotherapy arm and 105 in the darunavir triple-therapy arm ) . Baseline characteristics were well balanced between the two treatment groups . At week 96 , in intent-to-treat analysis , 91/103 patients ( 88 % , 95 % CI 81 - 94 ) allocated to the darunavir/ritonavir monotherapy arm and 87/104 patients ( 84 % , 95 % CI 75 - 90 ) allocated to the darunavir triple-therapy arm achieved an HIV-1 viral load < 50 copies/mL , with no statistical difference between the two groups . Throughout the 96 week follow-up , 66/112 patients ( 59 % , 95 % CI 49 - 68 ) and 79/113 patients ( 70 % , 95 % CI 61 - 78 ) consistently had HIV-1 RNA < 50 copies/mL with darunavir/ritonavir monotherapy and darunavir/ritonavir triple therapy , respectively . CONCLUSIONS The MONOI study establishes darunavir/ritonavir monotherapy as durable and efficacious for maintaining virological suppression in HIV-1 patients . Darunavir/ritonavir monotherapy should be considered as a ( tailored ) treatment option for st and ard triple-therapy patients who have had a substantial period of viral suppression Background Traditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities , women of child-bearing potential , and intolerability to components of st and ard first line therapy . This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient population s. The ACTION study was a r and omized , open-label , multicenter , 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects . Results 279 HIV-infected subjects with HIV-1 RNA ( VL ) > 5000 but < 200,000 copies/mL ( c/mL ) and CD4 + count ≥ 100 cells/mm3 were r and omized ( 1:1 ) to receive abacavir sulfate/lamivudine/zidovudine ( ABC/3TC/ZDV ) twice-daily or atazanavir ( ATV ) once-daily plus lamivudine/zidovudine ( 3TC/ZDV ) twice-daily . Protocol -defined virologic failure was based on multiple failure criteria .Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62 % vs. 59 % of subjects achieving a VL < 50 c/mL at week 48 , [ ITT(E ) , M/S = F , 95 % CI : -5.9 , 10.4 ] . Similar results were observed in the 230 ( 82 % ) subjects with baseline VL<100,000 c/mL ( ABC/3TC/ZDV vs. ATV+3TC/ZDV ) , 66 % vs. 59 % ; 95 % CI : -5.6 , 19.5 . However , ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL ≥ 100,000 c/mL , 39 % vs. 60 % ; 95 % CI : -49.2 , 7.4 , respectively . Protocol -defined virologic failure was similar between groups . Conclusion ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks . In those with a baseline VL ≥ 100,000 c/mL , subjects in the ATV+3TC/ZDV showed better virologic efficacy . Both regimens offer benefits in select therapy-naïve subjects . Trial Registration [ Clinical Trials Identifier , NCT00082394 ] This r and omized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens ( n=79 ) or a change to the simplified regimen of abacavir-lamivudine-zidovudine ( n=84 ) in patients with suppressed human immunodeficiency virus type 1 ( HIV-1 ) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation . After a median follow-up of 84 weeks , virologic failure was 6 % in the continuation and 15 % in the simplified group ( P=.081 ) . Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure . Study treatment was discontinued because of adverse events in 20 % of the continuation and 7 % of the simplified group ( P=.021 ) . Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels ; however , this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen BACKGROUND We assessed the strategy of substituting nevirapine , efavirenz , or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 ( HIV-1 ) in whom virologic suppression had been achieved . METHODS We r and omly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine ( 155 patients ) , efavirenz ( 156 ) , or abacavir ( 149 ) . The primary end point was death , progression to the acquired immunodeficiency syndrome , or an increase in HIV-1 RNA levels to 200 copies or more per milliliter . RESULTS At 12 months , the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group , 6 percent in the efavirenz group , and 13 percent in the abacavir group ( P=0.10 according to an intention-to-treat analysis ) . HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication ( 72 percent ) , and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients . Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors . Fewer patients in the abacavir group ( 6 percent ) than in the nevirapine group ( 17 percent ) or the efavirenz group ( 17 percent ) discontinued the study medication because of adverse events ( P=0.01 ) . The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group , but the prevalence of clinical lipodystrophy did not change significantly in the three groups . CONCLUSIONS When therapy was switched from a protease inhibitor to nevirapine , efavirenz , or abacavir in patients with virologic suppression , there was a trend toward a higher rate of virologic failure among those given abacavir BACKGROUND Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection , but data from direct comparisons are limited . METHODS This r and omized , double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1 : zidovudine-lamivudine-abacavir , zidovudine-lamivudine plus efavirenz , and zidovudine-lamivudine-abacavir plus efavirenz . RESULTS We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 ( 71,434 ) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled . A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups . After a median follow-up of 32 weeks , 82 of 382 subjects in the triple-nucleoside group ( 21 percent ) and 85 of 765 of those in the combined efavirenz groups ( 11 percent ) had virologic failure ; the time to virologic failure was significantly shorter in the triple-nucleoside group ( P<0.001 ) . This difference was observed regardless of the pretreatment HIV-1 RNA stratum ( at least 100,000 copies per milliliter or below this level ; P < or = 0.001 for both comparisons ) . Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups . CONCLUSIONS In this trial of the initial treatment of HIV-1 infection , the triple-nucleoside combination of abacavir , zidovudine , and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides OBJECTIVE To compare the efficacy and safety of a triple nucleoside combination to a protease inhibitor-containing triple regimen as first-line antiretroviral therapy ( ART ) in HIV-1-infected patients . DESIGN Open-label study in HIV-1-infected ART-naive adults , r and omized to receive either Combivir ( lamivudine 150 mg/zidovudine 300 mg twice daily ) + abacavir ( 300 mg twice daily ) , or Combivir + nelfinavir ( 750 mg every 8 h ) for 48 weeks . Plasma HIV-1 RNA , CD4 cell count and adverse events were assessed at baseline and weeks 4 , 8 , 16 , 24 , 32 , 40 and 48 . RESULTS 195 subjects ( 131 men , 64 women ) , median age 34 years , were r and omized : 98 received combivir/abacavir and 97 combivir/nelfinavir . Baseline median plasma HIV-1 RNA was 4.2 log10 copies/ml [ Interquartile range ( IQR ) : 3.7 - 4.5.2 ] and 4.1 log10 copies/ml ( IQR : 3.8 - 4.6 ) , respectively . Baseline median CD4 cell count was 387 cells/mm3 ( IQR : 194 - 501 ) and 449 cells/mm3 ( IQR : 334 - 605 ) , respectively . Nine patients ( 3 vs 6 , respectively ) did not start treatment or did not have any available efficacy data . At week 48 , using the intent to treat analysis ( switch/missing equals failure ) , plasma HIV-1 RNA was < 50 copies/ml in 54/95 ( 57 % ) and 53/91 ( 58 % ) of subjects , respectively . Median CD4 increase was + 110 and + 120 cells/mm3 , respectively . Possible hypersensitivity reactions to abacavir were reported in four subjects ( 4 % ) . CONCLUSION The triple nucleoside combination combivir/abacavir is well tolerated as a first-line ART regimen in HIV-1-infected adults , with comparable antiviral activity to a nelfinavir-containing regimen at week 48 In a prospect i ve , open-label , 104-week study , patients who were infected with human immunodeficiency virus type 1 ( virus load , < 50 copies/mL ) and who were receiving protease inhibitor-based therapy were r and omly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz . Treatment failure , defined as virological failure ( virus load , > 500 copies/microL ) or any clinical or biochemical adverse event with a grade of > or=3 ( on the basis of the World Health Organization [ WHO ] or American Heart Association [ AHA ] scales ) , was the primary outcome measurement . Failure rates were more frequent in the group treated with protease inhibitors ( P<.01 ) , and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir . Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors . Fewer patients who received efavirenz experienced viral rebound . Among all groups , the mean increase in the CD4 cell count was 131 cells/microL ( P<.001 ) , with no significant difference between groups . This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients Background : Treatment simplification in antiretroviral-experienced patients receiving protease inhibitor (PI)-containing antiretroviral regimens seems safe , but r and omized trials have limited power to detect differences in virological rebound ( VR ) between different switch strategies . Methods : From the French Hospital Data base on HIV , we selected 2462 patients with undetectable viral load ( VL ) who switched from a first PI-containing antiretroviral combination ( cART ) to a combination containing efavirenz ( EFV ) , nevirapine ( NVP ) or abacavir ( ABC ) . Factors associated with VR and with immunological efficacy ( gain of ≥ 50 CD4 + cells/μl ) were identified by using Cox models . Results : The 12-month Kaplan – Meier probabilities of VR were 6.8 , 13.7 and 12.3 % in patients switching to EFV-cART , NVP-cART and ABC-cART , respectively . Factors associated with VR were female sex , younger age , antiretroviral exposure before the first cART , time on first cART , higher VL at first cART initiation , a stavudine/didanosine backbone ( rather than zidovudine/lamivudine ) after the switch , and a switch to NVP or ABC [ respective adjusted hazard ratio versus EFV : 1.53 ; 95 % confidence interval ( CI ) , 1.21–1.94 ; and 1.53 ; 95 % CI , 1.12–2.08 ] . When the analyses were restricted to patients who were antiretroviral-naive before their first cART , NVP ( but not ABC ) was associated with VR . Immunological outcomes did not differ among the three switch regimens . Conclusion : When VL is undetectable on a first PI-cART regimen , switching to an EFV-containing regimen is more likely to avoid VR than switching to an ABC or NVP-containing regimen . ABC may be an alternative to EFV for patients who were not exposed to antiretroviral before their first cART regimen , after checking for ABC resistance mutations Objective To assess the antiviral efficacy , safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor ( NRTI ) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor ( PI ) combination . Methods In an open-label , multicentre study , patients receiving 2NRTI plus PI for at least 6 months , with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening , were r and omly assigned to replace the PI with abacavir ( n = 105 ) or continue the same treatment ( n = 106 ) . Clinical assessment s included plasma HIV-1 RNA , chemistry , haematology , lymphocyte counts , and adverse event reports . Adherence to treatment was assessed by patient self-report . Results A significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm ( P = 0.03 ) while treatment failure was experienced by significantly more patients in the PI arm : 24 ( 23 % ) versus 12 ( 12 % ) ( P = 0.03 ) . Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms , respectively , whereas virological rebound was the cause in four versus two cases . Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm ( P < 0.001 and P = 0.035 , respectively ) . The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm . Conclusion The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression , significant improvements in lipid abnormalities and enhanced ease of dosing Background : Recently , the Data collection of Adverse events of Anti-HIV Drugs Group ( D : A : D ) described results from their international observational cohort of 33,347 HIV-1-infected individuals , suggesting unexpected increased risk of myocardial infa rct ion ( MI ) associated with abacavir ( ABC ) therapy [ relative rate 1.9 , 95 % confidence interval ( CI ) : 1.47 to 2.45 ; P = 0.0001 ] . To contribute to the scientific question , we summarized GlaxoSmithKline HIV clinical trial data to determine if a similar signal emerged . Methods : We compiled data from GlaxoSmithKline-sponsored clinical trials with ≥24 weeks of combination antiretroviral therapy comprising 14,174 HIV-infected adults who received ABC ( n = 9502 ; 7641 person-years ) or not ( n = 4672 ; 4267 person-years ) . Findings : Baseline demographics and HIV disease characteristics , including lipids and glucose values , were similar . MI rates were comparable among subjects exposed [ n = 16 ( 0.168 % ; CI : 0.096 to 0.273 ; 2.09 per 1000 person-years ) ] or not [ n = 11 ( 0.235 % ; CI : 0.118 to 0.421 ; 2.57 per 1000 person-years ) ] to ABC-containing therapy . Results of 12 trials with r and omization to ABC or not were consistent ( 2.15 per 1000 person-years vs. 4.10 per 1000 person-years ) . Interpretations : In this pooled summary , we observed few MI events overall and no excess risk of MI with ABC therapy . It is unclear why results from this data set seem discrepant to the Data collection of Adverse events of Anti-HIV Drugs data set , particularly , as the non-ABC MI event rate is similar . Further data are needed to evaluate any association between ABC and increased risk of MI Objective : To assess the virological , immunological and metabolic effects of switching from an efficacious first-line protease inhibitor (PI)-based HAART to a simplified triple nucleoside reverse transcriptase inhibitor ( NRTI ) regimen in children vertically infected with HIV . Design : Prospect i ve , open-label , before – after study of 20 vertically infected children with at least 12 consecutive months of undetectable viral load under a PI-based HAART and no previous history of NRTI treatment . Methods : At study entry , HAART was shifted to a triple-NRTI combination . Results : The children were aged 2 to 18 years ( median , 7.9 ) and were followed for 96 weeks . All were receiving a PI-based regimen for an average duration of 4 years before enrollment . At study entry , 12 patients ( 60 % ) switched to abacavir , 5 ( 25 % ) to lamivudine ; 2 ( 10 % ) to zidovudine and 2 to didanosine ( 10 % ) . All but one patient maintained plasma HIV RNA < 50 copies/ml during the entire follow-up . No immunological failure was observed at week 96 . A trend of normalization ( P < 0.001 ) of T cell receptor Vβ families of the CD8 cell subset was detected in 19/20 ( 95 % ) , with an increased HIV-specific CD8 T cell response ( P < 0.01 ) in 17/20 ( 85 % ) . Dyslipidaemia significantly improved during the follow up ( P < 0.001 ) . No new cases of lipodystrophy were detected . Conclusions : Switching to triple-NRTI regimens in selected HIV-infected children with an extremely low likelihood of harbouring nucleoside-associated mutations maintains viral suppression and immunological function , improving metabolic abnormalities and the effort to take medication for up to 96 weeks BACKGROUND Our objective was to compare the rate of viral rebound and therapy failure in patients receiving abacavir or efavirenz as the third drug ( in addition to 2 non-abacavir nucleosides ) in combination antiretroviral therapy ( cART ) and to compare the rate of metabolic alteration associated with these regimens . METHODS We conducted a multicohort prospect i ve observational study of human immunodeficiency virus-infected patients who had attained viral loads < or = 80 copies/mL while receiving cART , without having previously received antiretrovirals . The rates of virological rebound , therapy failure , and lipid-level alteration during follow-up were calculated as the number of events divided by person-years of follow-up ( PYFU ) . A multivariable analysis was performed using a Poisson regression model . RESULTS We studied a total of 744 patients ; the median age was 37 years , 27 % of the patients were female , and 41 % were heterosexual . There was a total of 854 PYFU spent receiving efavirenz and 285 spent receiving abacavir . The nucleoside reverse-transcriptase inhibitor pairs most frequently used were zidovudine/lamivudine ( 66 % of PYFU ) , stavudine/lamivudine ( 17.6 % ) , and stavudine/didanosine ( 5.4 % ) . The adjusted relative rates of virological failure and therapy failure for abacavir , compared with those for efavirenz , were 2.17 ( 95 % confidence interval [ CI ] , 1.12 - 4.18 ; P = .02 ) and 1.41 ( 95 % CI , 1.01 - 2.01 ; P = .05 ) , respectively . CONCLUSIONS Patients with virological suppression while receiving regimens containing abacavir appear more likely to experience virological and therapy failure than those receiving efavirenz as their third drug . Although this is a selected group of adherent patients , bias can not be ruled out , because this is a nonr and omized comparison BACKGROUND We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infa rct ion . It is not clear whether this association differs according to the class of antiretroviral drugs . We conducted a study to investigate the association of cumulative exposure to protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the risk of myocardial infa rct ion . METHODS We analyzed data collected through February 2005 from our prospect i ve observational study of 23,437 patients infected with the human immunodeficiency virus . The incidence rates of myocardial infa rct ion during the follow-up period were calculated , and the associations between myocardial infa rct ion and exposure to protease inhibitors or nonnucleoside reverse-transcriptase inhibitors were determined . RESULTS Three hundred forty-five patients had a myocardial infa rct ion during 94,469 person-years of observation . The incidence of myocardial infa rct ion increased from 1.53 per 1000 person-years in those not exposed to protease inhibitors to 6.01 per 1000 person-years in those exposed to protease inhibitors for more than 6 years . After adjustment for exposure to the other drug class and established cardiovascular risk factors ( excluding lipid levels ) , the relative rate of myocardial infa rct ion per year of protease-inhibitor exposure was 1.16 ( 95 % confidence interval [ CI ] , 1.10 to 1.23 ) , whereas the relative rate per year of exposure to nonnucleoside reverse-transcriptase inhibitors was 1.05 ( 95 % CI , 0.98 to 1.13 ) . Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 ( 95 % CI , 1.04 to 1.18 ) and 1.00 ( 95 % CI , 0.93 to 1.09 ) , respectively . CONCLUSIONS Increased exposure to protease inhibitors is associated with an increased risk of myocardial infa rct ion , which is partly explained by dyslipidemia . We found no evidence of such an association for nonnucleoside reverse-transcriptase inhibitors ; however , the number of person-years of observation for exposure to this class of drug was less than that for exposure to protease inhibitors OBJECTIVE To evaluate the change in bone mineral density ( BMD ) at specific sites in patients initiating antiretroviral therapy in a sub study of the ANRS 121 trial . METHODS Antiretroviral-naive patients were r and omized ( 2 : 1 : 1 ) into three treatment strategy arms : a nonnucleoside reverse transcriptase inhibitor ( NNRTI ) and a boosted protease inhibitor ( PI/r ) , a PI/r and two nucleoside reverse transcriptase inhibitors ( NRTIs ) or an NNRTI and NRTIs . Hip and lumbar spine st and ardized BMD were evaluated at baseline and week 48 by dual X-ray absorptiometry by a central reading laboratory . RESULTS Seventy-one patients were enrolled : 36 in the PI/r and NNRTI , 19 in the PI/r and NRTIs and 16 in the NNRTI and NRTIs arms . Baseline characteristics were [ median ( interquartile range ) ] : male ( 77 % ) , age 40 years ( 33 - 49 ) , 69 % white , 58 % smokers , BMI 23 kg/m2 ( 21 - 24 ) , CD4 cell count 219 cells/microl ( 144 - 285 ) . In the arms with NRTIs , 86 % of patients received zidovudine/lamivudine . At baseline , 31 % had osteopenia and 3 % had osteoporosis . At week 48 , there was a mean change in BMD of -4.1 + /- 3.9 % at lumbar spine and -2.8 + /- 4.7 % at hip ( both P < or = 0.001 ) . The decrease of BMD at lumbar spine was significantly worse in the PI/r and NNRTI arm ( -4.4 + /- 3.4 % ) and in the PI/r and NRTIs arm ( -5.8 + /- 4.5 % ) compared with the NNRTI and NRTIs arm ( -1.5 + /- 2.9 % ) , P = 0.007 and P = 0.001 , respectively . CONCLUSION BMD was impaired in 34 % of patients , before starting any antiretrovirals . After 1 year , the decrease in lumbar spine BMD was more pronounced in patients receiving either PI/r-containing regimen compared with NNRTI and NRTIs . BMD at specific sites should be monitored during lifelong antiretroviral therapy Maintenance with a triple nucleoside reverse transcriptase Inhibitor ( NRTI ) regimen after successful induction with a dual NRTI/protease inhibitor ( PI ) combination may be advantageous , because of low pill burden , favorable lipids , and less drug interactions . This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested . We performed a r and omized , open-label , multicenter , 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 < or=350 cells/mm(3 ) and HIV-1 RNA concentrations ( viral load [ VL ] ) greater than 30,000 copies per milliliter . Patients were r and omized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination . Eligible subjects switched to abacavir/lamivudine/zidovudine ( TZV ) or continued the PI-containing regimen . Here we present the 48-week data with virologic success rate ( failure : VL > 50 copies per milliliter ) . Two hundred seven patients had similar baseline ( BL ) characteristics : median CD4 180 cells/mm(3 ) , median VL 5.19 log(10 ) copies per milliliter . One hundred twenty subjects ( 58 % ) met r and omization criteria . Baseline VL differed significantly between dropouts and r and omized subjects ( median 5.41 versus 5.06 log(10 ) copies per milliliter , p = 0.017 ) , as did CD4 cells ( median 160 and 200 cells/mm(3 ) , p = 0.044 ) . Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI . At week 48 , 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression ( log rank test ; p = 0.379 ) . CD4 counts increased significantly in both arms . In ART-naïve patients , TZV maintenance had similar antiviral efficacy compared to continued st and ard ART at 48 weeks after baseline . Patients on successful st and ard ART can be safely switched to a NRTI-only regimen , at least for the tested time period Objectives : To assess the virologic noninferiority of an antiretroviral treatment simplification with coformulated zidovudine/lamivudine/abacavir ( group 1 ) vs. coformulated zidovudine/lamivudine plus nevirapine ( group 2 ) in HIV-1-infected patients receiving successful first-line highly active antiretroviral therapy . Methods : This is a prospect i ve , multicenter , open-label , comparative , r and omized , noninferiority study . A delta of 15 % for differences in virologic suppression < 200 copies/mL between groups was prespecified with a 1-sided 0.025 significance level . Results : A total of 134 patients were included into this study : 68 were allocated to group 1 and 66 to group 2 . By intention-to-treat analysis ( switch equals failure ) , the percentage of virologic suppression < 200 copies/mL ( < 50 copies/mL ) at week 48 was 71.0 % ( 65.1 % ) and 73.0 % ( 63.3 % ) in groups 1 and 2 , respectively ( estimate for differences [ < 200 copies/mL ] : −2.1 , 95 % CI : −17.4 - 13.1 , P = 0.783 ) . Thirteen and 14 patients in groups 1 and 2 , respectively , discontinued therapy due to adverse events . Dyslipidemia improved in both groups , with a higher improvement in low-density lipoprotein cholesterol ( P = 0.049 ) in group 1 . Conclusions : Group 1 is not inferior to group 2 regarding virologic suppression < 200 copies/mL. Both strategies improve lipid profile OBJECTIVE To assess the antiviral efficacy , safety , and adherence in subjects who switched to Trizivir following long-term HIV-1 RNA suppression . STUDY DESIGN A r and omized , open-label , multicentre , 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months , with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening . METHODS Subjects were r and omized 1:1 to continue their current treatment or to switch to a simplified treatment with Trizivir administered twice daily . Assessment s included plasma HIV-1 RNA , lymphocyte counts , clinical laboratory evaluations , adverse events , and adherence to treatment ( obtained via subject self-report ) . Treatment failure was defined as a plasma viral load of > /= 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of r and omized treatment . RESULTS At week 48 , the proportion of treatment failures in Trizivir arm ( 23/106 , 22 % ) was noninferior to that observed in continued arm ( 23/103 , 22 % ) with a treatment difference stratified by prior ART of 1.2%[-10.1 ; 12.5 ] . Incidence of adverse events was similar in both treatment groups . The incidence of possible hypersensitivity reaction in the Trizivir trade mark arm was 10 % . Significant reductions in cholesterol and triglyceride plasma levels were observed in the Trizivir arm ( P < 0.001 and P = 0.006 , respectively ) . CONCLUSION Switching to Trizivir offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy SUMMARY Objective : An equivalence ( non-inferiority ) trial comparing antiviral response , tolerability , and adherence with a triple nucleoside regimen containing abacavir 300 mg ( ABC ) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet ( COM ) twice daily vs. a regimen containing the protease inhibitor indinavir ( IDV ) 800 mg three times daily plus COM twice daily ( IDV/COM ) in antiretroviral-naïve , HIV-infected patients . Methods : Adult patients with plasma HIV-1 RNA levels ≥ 5000 copies/mL and CD4 + cell counts ≥ 100 cells/mm3 were r and omized to receive open-label ABC/COM ( n = 169 ) or IDV/COM ( n = 173 ) for 48 weeks . The intent-to-treat ( ITT ) population was the primary population evaluated . ITT : switch/missing equals failure ( ITT : S/M = F ) and as-treated ( AT ) analyses were used for assessing the proportion of patients achieving plasma HIV-1 RNA level < 400 and < 50 copies/mL at each clinic visit . In the ITT : S/M = F analysis , patients who switched treatment or had missing values were considered treatment failures ; the AT analysis examined virologic data only while patients received study treatment . ABC/COM was considered equivalent ( non-inferior ) to IDV/COM if the lower limit of the 95 % confidence intervals ( CIs ) about the difference in proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA < 400 copies/mL exceeded –15 % at week 48 . Results : The study population was diverse with respect to ethnicity ( 38 % Asian , 27 % Hispanic , 28 % white , 3 % black , 4 % other ) and gender ( 39 % women , 61 % men ) . Baseline median HIV-1 RNA was 4.80 log10 copies/mL and CD4 + cell count was 315 cells/mm3 . ABC/COM met the criterion of equivalence to IDV/COM . In the ITT : S/M = F analysis at Week 48 , a greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL ( 66 % [ 109/164 ] vs. 50 % [ 82/165 ] ; treatment difference 16.6 % , 95 % CI ( 6.0 , 27.2 ) , p = 0.002 ) and HIV-1 RNA < 50 copies/mL ( 60 % [ 99/164 ] vs. 50 % [ 83/165 ] ; treatment difference 9.6 % , 95 % CI [ –1.1 , 20.2 ] ) , whereas the AT analysis showed similar proportions achieving these endpoints ( < 400 copies/mL : 85 vs. 83 % ; < 50 copies/mL : 79 vs 81 % ) . Comparable proportions of patients with screening HIV-1 RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL ( ABC/COM : 60 % [ 35/58 ] ; IDV/COM : 51 % [ 33/65 ] ; treatment difference 9.6 % , 95 % CI [ –7.9 , 27.1 ] ; ITT : S/M = F analysis ) . A significantly greater proportion taking ABC/COM were ≥ 95 % adherent ( 72 % [ 109/151 ] vs. 45 % [ 70/154 ] with IDV/COM , p < 0.001 ) . Median increases from baseline in CD4 + cell counts were similar in the two treatment groups ( + 148 vs. + 152 cells/mm3 ) . Significantly more patients on IDV/COM reported drug-related adverse events ( 87 % [ 142/165 ] vs. 65 % [ 108/164 ] with ABC/COM , p < 0.001 ) , similar proportions discontinued treatment due to adverse events ( 13 vs. 10 % ) , and a slightly greater proportion in the ABC/COM group reported serious adverse events ( 13 vs. 8 % ) . About half of the latter comprised suspected ABC-related hypersensitivity reactions ( overall rate , 6 % ) . Most adverse events were gastrointestinal in nature in both treatment groups . Conclusion : ABC/COM was at least equivalent to IDV/COM over 48 weeks in the treatment of antiretroviral-naïve patients . ABC/COM was associated with a significantly higher adherence rate and lower incidence of drug-related adverse events than IDV/COM . The study was limited in that it was not powered to determine equivalence of treatments within high vs. low viral load strata , adherence was not monitored electronically , and bias could not be ruled out due to the open-label study design BACKGROUND Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy ( ART ) , avoiding hepatotoxicity and interactions with anti-tuberculosis therapy , and sparing two drug classes for second-line ART . Concerns exist about virological potency ; efficacy has not been assessed in Africa . METHODS A safety trial comparing nevirapine with abacavir was conducted in two Ug and an Development of Antiretroviral Therapy in Africa ( DART ) centres : 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts < 200 cells/microL were r and omized to zidovudine/lamivudine plus abacavir or nevirapine ( placebo-controlled to 24-week primary toxicity endpoint , and then open-label ) . Documented World Health Organization ( WHO ) stage 4 events were independently review ed and plasma HIV-1 RNA assayed retrospectively . Exploratory efficacy analyses are intention-to-treat . RESULTS The median pre-ART CD4 count was 99 cells/microL , and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants ( 94 % ) completed 48 weeks of follow-up , 25 ( 4 % ) died and 12 ( 2 % ) were lost to follow-up . The r and omized drug was substituted in 21 participants ( 7 % ) receiving abacavir vs. 34 ( 11 % ) receiving nevirapine ( P=0.09 ) . At 48 weeks , 62 % of participants receiving abacavir vs. 77 % of those receiving nevirapine had viral loads < 50 copies/mL ( P<0.001 ) , and mean CD4 count increases from baseline were + 147 vs. + 173 cells/microL , respectively ( P=0.006 ) . Nine participants ( 3 % ) receiving abacavir vs. 16 ( 5 % ) receiving nevirapine died [ hazard ratio ( HR ) 0.55 ; 95 % confidence interval ( CI ) 0.24 - 1.25 ; P=0.15 ] ; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died ( HR=0.60 ; 95 % CI 0.34 - 1.05 ; P=0.07 ) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died ( HR=0.67 ; 95 % CI 0.46 - 0.96 ; P=0.03 ) . Seventy-one participants ( 24 % ) receiving abacavir experienced 91 grade 4 adverse events compared with 130 events in 109 participants ( 36 % ) on nevirapine ( P<0.001 ) . CONCLUSIONS The clear virological/immunological superiority of nevirapine over abacavir was not reflected in clinical outcomes over 48 weeks . The inability of CD4 cell count/viral load to predict initial clinical treatment efficacy is unexplained and requires further evaluation BACKGROUND Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infa rct ion in HIV-infected individuals is unclear . Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infa rct ion in a large , prospect i ve observational cohort of HIV-infected patients . METHODS We used Poisson regression models to quantify the relation between cumulative , recent ( currently or within the preceding 6 months ) , and past use of zidovudine , didanosine , stavudine , lamivudine , and abacavir and development of myocardial infa rct ion in 33 347 patients enrolled in the D : A : D study . We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy , cohort , calendar year , and use of other antiretrovirals . FINDINGS Over 157,912 person-years , 517 patients had a myocardial infa rct ion . We found no associations between the rate of myocardial infa rct ion and cumulative or recent use of zidovudine , stavudine , or lamivudine . By contrast , recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infa rct ion ( compared with those with no recent use of the drugs , relative rate 1.90 , 95 % CI 1.47 - 2.45 [ p=0.0001 ] with abacavir and 1.49 , 1.14 - 1.95 [ p=0.003 ] with didanosine ) ; rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs . After adjustment for predicted 10-year risk of coronary heart disease , recent use of both didanosine and abacavir remained associated with increased rates of myocardial infa rct ion ( 1.49 , 1.14 - 1.95 [ p=0.004 ] with didanosine ; 1.89 , 1.47 - 2.45 [ p=0.0001 ] with abacavir ) . INTERPRETATION There exists an increased risk of myocardial infa rct ion in patients exposed to abacavir and didanosine within the preceding 6 months . The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation |
11,232 | 26,366,096 | The findings of this meta- analysis indicate that , based on available information , dietary fiber , whole grains , carbohydrate , GI , and GL are not associated with the risk of prostate cancer | BACKGROUND The relationships between dietary fiber , whole grains , carbohydrate , glycemic index ( GI ) , glycemic load ( GL ) , and prostate cancer risk are unclear .
We conducted a systematic review and meta- analysis to investigate these associations . | Purpose : Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I ( IGF-I ) , both potent prostate cancer mitogens . We tested whether varying dietary carbohydrate and fat , without energy restriction relative to comparison diets , would slow tumor growth and reduce serum insulin , IGF-I , and other molecular mediators of prostate cancer in a xenograft model . Experimental Design : Individually caged male severe combined immunodeficient mice ( n = 130 ) were r and omly assigned to one of three diets ( described as percent total calories ) : very high-fat/no-carbohydrate ketogenic diet ( NCKD : 83 % fat , 0 % carbohydrate , 17 % protein ) , low-fat/high-carbohydrate diet ( LFD : 12 % fat , 71 % carbohydrate , 17 % protein ) , or high-fat/moderate-carbohydrate diet ( MCD : 40 % fat , 43 % carbohydrate , 17 % protein ) . Mice were fed to maintain similar average body weights among groups . Following a preliminary feeding period , mice were injected with 1 × 106 LNCaP cells ( day 0 ) and sacrificed when tumors were ≥1,000 mm3 . Results : Two days before tumor injection , median NCKD body weight was 2.4 g ( 10 % ) and 2.1 g ( 8 % ) greater than the LFD and MCD groups , respectively ( P < 0.0001 ) . Diet was significantly associated with overall survival ( log-rank P = 0.004 ) . Relative to MCD , survival was significantly prolonged for the LFD ( hazard ratio , 0.49 ; 95 % confidence interval , 0.29 - 0.79 ; P = 0.004 ) and NCKD groups ( hazard ratio , 0.59 ; 95 % confidence interval , 0.37 - 0.93 ; P = 0.02 ) . Median serum insulin , IGF-I , IGF-I/IGF binding protein-1 ratio , and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice . Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis , inflammation , insulin resistance , and obesity were also significantly reduced in NCKD relative to MCD tumors . Conclusions : These results support further pre clinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans Abstract Background : Calcium , phosphorus , fructose , and animal protein are hypothesized to be associated with prostate cancer risk , potentially via their influence on 1,25-dihydroxyvitamin D3 . We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study ( ATBC Study ) . Material s and methods : The ATBC Study was a r and omized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers ; 27,062 of the men completed a food-use question naire at baseline , and comprise the current study population . There were 184 incident clinical ( stage 2–4 ) prostate cancer cases diagnosed between 1985 and 1993 . We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer . Results : We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk . However , men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 ( 95 % CI 0.3–1.0 ) compared to men with lower intakes of both nutrients , adjusting for age , smoking , body mass index , total energy , education , and supplementation group . Of the other foods and nutrients examined , none was significantly associated with risk . Discussion : This study provides , at best , only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk , but suggests that there may be an interaction between these nutrients Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Dietary fiber may reduce the risk of prostate cancer , possibly by increasing circulating concentrations of sex hormone-binding globulin and improving insulin sensitivity . However , results from previous epidemiologic studies of fiber intake and prostate cancer are inconsistent , and to our knowledge , no study has comprehensively evaluated the effects of soluble and insoluble fiber on prostate cancer in Asia . OBJECTIVE The objective was to examine the association between fiber intake and prostate cancer in Japanese men . DESIGN We conducted a population -based prospect i ve study in 43,435 Japanese men aged 45 - 74 y. Participants responded to a vali date d question naire , which included 138 food items . Follow-up was from 1995 through 2009 . HRs and 95 % CIs of incidence were calculated according to quartiles of fiber intake . RESULTS During the 11.6-y follow-up , of the 825 men newly diagnosed with prostate cancer , 213 had advanced-stage cancer , 582 had organ-localized disease , and 30 had an undetermined stage of disease . Among them , 217 cases were detected by subjective symptoms . Total fiber was not associated with total or advanced prostate cancer , with respective multivariable HRs for the highest and lowest quartiles of 1.00 ( 95 % CI : 0.77 , 1.29 ; P-trend = 0.97 ) and 0.67 ( 95 % CI : 0.42 , 1.07 ; P-trend = 0.30 ) . Total fiber and insoluble fiber intake were associated with a decreased risk of advanced cancers detected by subjective symptoms , with multivariate HRs ( 95 % CIs ) across increasing quartiles of 1.00 , 0.58 , 0.62 , and 0.44 ( 0.21 , 0.92 ; P-trend = 0.05 ) for total fiber and 1.00 , 0.60 , 0.52 , and 0.46 ( 0.22 , 0.93 ; P-trend = 0.04 ) for insoluble fiber . Soluble fiber intake showed no association with prostate cancer . CONCLUSIONS Dietary fiber is inversely associated with advanced prostate cancer detected by subjective symptoms even among population s with relatively low intake , such as Japanese . These results suggest that a very low intake of dietary fiber is associated with an increased risk of prostate cancer Epidemiological data on most cancer sites suggest that consumption of plant foods , which contain high levels of antioxidants , might slow or prevent the appearance of cancer . We used data from three case-control studies to test this hypothesis . The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario , Quebec , and British Columbia . Dietary information was collected by an in-person interview with a detailed quantitative dietary history . Unconditional logistic regression analyses were performed to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . A decreasing , statistically significant association was found with increasing intakes of green vegetables ( OR = 0.54 , 95 % CI = 0.40 - 0.71 for 4th quartile ) , tomatoes ( OR = 0.64 , 95 % CI = 0.45 - 0.91 ) , beans/lentils/nuts ( OR = 0.69 , 95 % CI = 0.53 - 0.91 ) , and cruciferous vegetables ( OR = 0.69 , 95 % CI = 0.52 - 0.91 for 3rd quartile ) . Higher intakes of fruit were associated with higher ORs ( OR = 1.51 , 95 % CI = 1.14 - 2.01 for 4th quartile ) , an effect that was seen for total fruit and citrus fruit , as well as for all other noncitrus fruits . Among the grains , refined-grain bread intake was associated with a decrease in risk ( OR = 0.65 for 4th quartile ) , whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer . Of all the antioxidant nutrients studied , the ORs were higher with higher intakes of cryptoxanthin ( OR = 1.44 , 95 % CI = 1.09 - 1.89 for 4th quartile ) . Exposure to certain dietary components of plant origin , which are potentially modifiable , indicates the theoretical scope for reducing the risk from prostate cancer . Future experimental studies or trials are warranted for further underst and ing Objective To evaluate the associations between dietary carbohydrate , glycemic index ( GI ) , glycemic load ( GL ) , and incident prostate cancer in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial ( PLCO ) cohort . Methods Between September 1993 and September 2000 , 38,343 men were r and omized to the screening arm of the trial at one of 10 PLCO centers . A food frequency question naire administered at baseline assessed usual dietary intake over the preceding 12 months . Prostate cancer was ascertained by medical follow-up of suspicious screening results and annual mailed question naires and confirmed with medical records . Cox proportional hazards regression was used to model the associations of carbohydrate , GI , and GL with prostate cancer risk . Results During follow-up ( median = 9.2 years ) , 2,436 incident prostate cancers were identified among 30,482 eligible participants . Overall , there were no associations of baseline carbohydrate , GI , or GL with incident prostate cancer in minimally or fully adjusted models . There were no associations when the 228 advanced and 2,208 non-advanced cancers were analyzed separately . Conclusions Dietary carbohydrate , GI , and GL were not associated with incident prostate cancer in PLCO . The narrow range of GI in this cohort may have limited our ability to detect associations , an issue that future studies should address Objective High intake of whole-grain products may protect against prostate cancer , but overall evidence is limited and inconclusive . The aim of the present study was to investigate the relationship between the intake of whole-grain products and risk of prostate cancer in a large prospect i ve cohort . Methods A total of 26,691 men aged 50–64 years participated in the Diet , Cancer and Health cohort study and provided information about diet and potential prostate cancer risk factors . During a median follow-up of 12.4 years , we identified 1,081 prostate cancer cases . Associations between whole-grain product intake and prostate cancer incidence were analyzed using Cox ’s regression model . Results Overall , there was no association between total intake of whole-grain products and prostate cancer risk ( adjusted incidence rate ratio per 50 g day−1 : 1.00 ( 95 % confidence interval : 0.96 , 1.05 ) ) as well as between intake of the specific whole-grain products : whole-grain rye bread , whole-grain bread , and oatmeal , and risk of prostate cancer . No risk estimates did differ according to either stage or grade of disease . Conclusions Results from this prospect i ve study suggest that higher intakes of total or specific whole-grain products are not associated with risk of prostate cancer in a population of Danish middle-aged men The role of diet in the etiology of prostate cancer remains unclear , because results from several case‐control and cohort studies on fat intake and risk of prostate cancer have been inconsistent ; few of the studies have adjusted the results for caloric intake . To examine the relationship between energy , intake of several nutrients and risk of prostate cancer ( all stages combined and advanced stages separately ) , we conducted a population ‐based case‐control study in Örebro County , Sweden , from 1989 through 1994 . A total of 526 patients with newly diagnosed prostate cancer and 536 controls , r and omly selected from the population register and frequency‐matched by age , were included in the analyses . Information about dietary intake was obtained from a self‐administered semi‐quantitative food frequency question naire . Odds ratios with 95 % confidence intervals were estimated by unconditional logistic regression . In age‐adjusted analyses , there were positive associations of prostate cancer ( all stages combined ) risk with total energy intake as well as intake of total fat ( saturated and monounsaturated ) , protein , retinol and zinc . The positive association with energy intake was stronger for advanced cancer , with an excess risk of 70 % for the highest quartile vs. the lowest . After adjustment for energy intake , there was no apparent association of prostate cancers ( all stages combined ) with any of the investigated nutrients . However , a weak positive association between intake of retinol and advanced cancer was observed . We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer . © 1996 Wiley‐Liss , Although experimental data suggest a potentially protective involvement of dietary fiber in prostate carcinogenesis , very few prospect i ve studies have investigated the relation between dietary fiber intake and prostate cancer risk , and those have had inconsistent results . Our objective was to study the association between dietary fiber intake ( overall , insoluble , soluble , and from different sources , such as cereals , vegetables , fruits , and legumes ) and prostate cancer risk . Stratifications by excess weight status , insulin-like growth factors , and amount of alcohol intake were also considered . This prospect i ve analysis included 3313 men from the Supplémentation en Vitamines et Minéraux Antioxydants ( SU.VI.MAX ) cohort who completed at least 3 24-h dietary records . One hundred thirty-nine incident prostate cancers were diagnosed between 1994 and 2007 ( median follow-up of 12.6 y ) . Associations between quartiles of energy-adjusted dietary fiber intake and prostate cancer risk were characterized by multivariate Cox proportional hazards models . Prostate cancer risk was inversely associated with total dietary fiber intake ( HR of quartile 4 vs. quartile 1 = 0.47 ; 95 % CI : 0.27 , 0.81 ; P = 0.001 ) , insoluble ( HR = 0.46 ; 95 % CI : 0.27 , 0.78 ; P = 0.001 ) , and legume ( HR = 0.55 ; 95 % CI : 0.32 , 0.95 ; P = 0.04 ) fiber intakes . In contrast , we found no association between prostate cancer risk and soluble ( P = 0.1 ) , cereal ( P = 0.7 ) , vegetable ( P = 0.9 ) , and fruit ( P = 0.4 ) fiber intakes . In conclusion , dietary fiber intake ( total , insoluble , and from legumes but not soluble or from cereals , vegetables , and fruits ) was inversely associated with prostate cancer risk , consistent with mechanistic data |
11,233 | 18,945,258 | A substantial proportion of UC flares and medical costs of UC are attributable to 5-ASA non-adherence . | BACKGROUND Ulcerative colitis ( UC ) can be maintained in remission with 5-aminosalicylic acid ( 5-ASA ) medications , but frequent non-adherence by patients who are feeling well has been associated with more frequent flares of colitis .
AIM To perform a systematic review of the published literature and unpublished r and omized clinical trials ( RCTs ) regarding the impact of non-adherence with 5-ASA medications on the incidence of UC flares and costs of care . | This study compares patient compliance with once- and twice-daily formulations of 5-isosorbide mononitrate . A total of 31 patients ( 20 men and 11 women ) with stable angina pectoris were r and omized to receive either 60 mg 5-isosorbide mononitrate in a controlled release formulation once daily , or 20 mg 5-isosorbide mononitrate twice daily . The results indicated that compliance assessed using the electronic Medication Event Monitoring System ( MEMS ® ) was better with the once-daily than with the twice-daily formulation ; patients on the once-daily regimen performed better with respect to the total number of bottle openings , the number of openings per day , the timing of openings and the intervals between openings . The apparently superior compliance with the once-daily regimen appeared to be reflected in better efficacy ; patients on the once-daily regimen experienced fewer angina attacks ( a mean of 1.7 per 7 days , compared with 3.3 per 7 days for patients on the twice-daily regimen ) and used fewer nitroglycerin tablets than those on the twice-daily regimen PURPOSE We conducted a prospect i ve study to determine the effects of nonadherence with mesalamine among patients with quiescent ulcerative colitis . METHODS We followed a cohort of 99 consecutive patients who had ulcerative colitis in remission for more than 6 months and who were taking maintenance mesalamine . Medication adherence rates were calculated based on pharmacy records and a vali date d formula . Nonadherence was defined as refilling less than 80 % of prescribed medication . Patients were followed prospect ively and evaluated either in clinic or via telephone at 6 , 12 , and 24 months . The primary outcome was clinical recurrence of ulcerative colitis . Proportional hazards models were used to adjust for confounders . RESULTS At 6 months , 12 patients ( 12 % ) had clinical recurrence of disease symptoms , all of whom were nonadherent with medication . At 12 months , 19 of 86 patients had recurrent disease , 13 ( 68 % ) of whom were nonadherent . Patients who were not adherent with medication had more than a fivefold greater risk of recurrence than adherent patients ( hazard ratio = 5.5 ; 95 % confidence interval : 2.3 to 13 ; P < 0.001 ) . CONCLUSION Nonadherence with medication increases the risk of clinical relapse among patients with quiescent ulcerative colitis . Future research should be directed at behavioral interventions to improve adherence BACKGROUND & AIMS This study was conducted to assess , in a small sample , the short-term outcomes of once-daily mesalamine versus conventional dosing in maintaining quiescent ulcerative colitis ( UC ) and to assess adherence rates with both regimens . METHODS Consecutive patients were r and omly assigned to either a once-daily regimen , or they continued current conventional regimen ( twice daily or 3 times daily ) . Patients were assessed at 3 months and 6 months . At each point , a clinical symptom disease score was obtained using patient question naires , and medication rates via pharmacy data . Adherence was defined as consumption of > 80 % of prescribed medication . Information was collected by an investigator blinded to treatment regimen . RESULTS Twenty-two patients were enrolled in the study , 12 in the once-daily group ( QD ) and 10 in the conventional group ( CD ) . At 3 months , no patients had experienced a relapse . All of the patients in the QD group and 70 % of patients in the CD group were adherent ( P = 0.04 ) . The average amount of medication consumed in the QD group was significantly higher than in the CD group ( 90 % vs. 75 % , P = 0.02 ) . At 6 months , 2 patients ( 1 patient from each group ) experienced a clinical relapse ( P = 0.76 ) . Seventy-five percent vs. 70 % of patients were adherent ( P = 0.8 ) ; the amount of medication taken approached significance ( 90 % vs. 76 % , P = 0.07 ) . All patients in the QD group reported being either " very satisfied " or " satisfied " with their regimen . CONCLUSIONS In this r and omized pilot trial , patients taking once-daily mesalamine had outcomes similar to those for patients on conventional regimens . A larger trial is warranted to assess whether true differences between regimens exist A large , Internet‐based survey of a r and om sample of members of the Crohn 's and Colitis Foundation of America was undertaken to gain knowledge and underst and ing of patients ' experiences with ulcerative colitis and first‐line therapies . From 49,410 invitations to participate , 1,595 usable responses were received from patients with ulcerative colitis . Patients were prescribed a range of aminosalicylates for their ulcerative colitis . Treatments with the highest proportion of satisfied patients were associated with highest remission rates . Forty‐three percent of patients considered their disease to be in remission ; however , 74 % reported disease relapse during the previous 12 months . Over 60 % of patients reported that they were noncompliant with prescribed aminosalicylate dosing schedules , with reasons attributed to frequency of dosing , the number of pills , and the inconvenience of the medication . Many respondents reported that they had made significant lifestyle changes because of their ulcerative colitis , including spending more time at home ( 46 % ) and participating in fewer social activities ( 37 % ) . When asked to describe their ideal treatment , patients considered high efficacy ( 97 % ) , lack of side effects ( 74 % ) , nonparenteral dosing ( 46 % ) , nonrectal dosing ( 36 % ) , low cost ( 23 % ) , fewer pills ( 23 % ) , and less frequent dosing ( 23 % ) as “ very important . ” This study demonstrates that continuous symptomatic remission is central to patient satisfaction and that patients find currently available aminosalicylates to be inconvenient . Patients ' ideal therapy would be an effective , oral formulation with fewer tablets , less frequent dosing , and minimal side effects . Development of such a therapy would , therefore , potentially improve both patient compliance and overall treatment success OBJECTIVE : The aim of this study was to identify determinants of nonadherence to medication in out patients with established inflammatory bowel disease ( IBD ) . METHODS : Ten gastroenterologists and 153 of their IBD patients participated in this prospect i ve study . Demographic , clinical , and psychosocial characteristics , as well as patient-physician discordance , were assessed at an office visit . Nonadherence to medication was assessed 2 wk later . Separate generalized estimating equations were used to identify determinants of nonadherence . RESULTS : Physicians averaged 47.9 yr in age ( range 30.1–57.5 yr ) , and 90 % were male . Patients averaged 37.0 yr ( SD = 15.1 ) , and 87 ( 56.9 % ) were female . In all , 63 patients ( 41.2 % ) were nonadherent to medication ; of these , 51 ( 81.0 % ) indicated unintentional nonadherence , 23 ( 36.5 % ) intentional nonadherence , and 11 ( 17.5 % ) both . Overall nonadherence was predicted by disease activity ( OR = 0.55 , p = 0.0022 ) , new patient status ( OR = 2.14 , p = 0.0394 ) , disease duration ( OR = 0.50 , p = 0.0001 ) , and scheduling a follow-up appointment ( OR = 0.30 , p = 0.0059 ) , whereas higher discordance on well-being was predictive only in psychologically nondistressed patients ( p = 0.0026 for interaction ) . Unintentional nonadherence was predicted by age ( OR = 0.97 , p = 0.0072 ) , new patient status ( OR = 2.80 , p = 0239 ) , and higher discordance on well-being in psychologically nondistressed patients ( p = 0.0504 ) . Intentional nonadherence was predicted by disease duration ( OR = 0.55 , p = 0032 ) , scheduling a follow-up appointment ( OR = 0.12 , p = 0.0001 ) , certainty that medication would be helpful ( OR = 0.99 , p = 0.0409 ) , and total patient-physician discordance ( OR = 1.59 , p = .0120 ) . CONCLUSIONS : These findings suggest that the therapeutic relationship , as well as individual clinical and psychosocial characteristics , influence adherence to medication The objective of this study was to determine the relationship between prescribed daily dose frequency and patient medication compliance . The medication compliance of 105 patients receiving antihypertensive medications was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal . Inaccurate compliance estimates derived using the simple pill count method were thereby avoided . Compliance was defined as the percent of days during which the prescribed number of doses were removed . Compliance improved from 59.0 % on a three-time daily regimen to 83.6 % on a once-daily regimen . Thus , compliance improves dramatically as prescribed dose frequency decreases . Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency Recent studies have shown a low adherence rate to maintenance treatment in patients with inflammatory bowel disease ( IBD ) . We sought to assess the medication-taking behavior in a cohort of patients with IBD . We prospect ively included IBD patients from the outpatient clinic who agreed to answer a question naire about prescribed treatment and adherence . Physicians registered clinical data including prescribed medications . Two hundred fourteen patients ( 115 Crohn 's disease/99 ulcerative colitis ) were included . The most prescribed medications were oral mesalazine ( 56.5 % ) and immunomodulators ( 41.1 % ) . Forty-three percent of patients admitted to occasionally forgetting to take their medication but only 7.5 % of them did it voluntary . Oral mesalazine and azathioprine were the drugs with the poorest compliance , with nonadherence rates of 45 % and 25 % of the total prescribed doses , respectively . The only factor associated with a better adherence was a more complicated course of the disease — steroid dependency , steroid refractoriness , need for infliximab treatment , hospitalization , or surgery ( P=.02 ) . Twenty percent of patients admitted to self-medicating . An important proportion of patients with IBD admit to forget some doses of the prescribed medication in the setting of a specialized unit of a referral centre BACKGROUND Patients with inflammatory bowel disease ( IBD ) suffer physical dysfunction and impaired quality of life ( QOL ) , and need frequent health care . They often lack knowledge about their disease and desire more education . Educational interventions for other chronic diseases have demonstrated reduced health care use and increased knowledge , medication adherence and QOL . METHOD Sixty-nine participants were r and omly assigned to formal IBD education and st and ard of care ( pamphlets and ad hoc physician education ) or st and ard of care alone . Assessment of IBD knowledge and QOL occurred at baseline , immediately posteducation and eight weeks posteducation . Participants documented medication adherence and health care use in diaries . Patient satisfaction was assessed at the end of the study . RESULTS The education group had higher knowledge scores ( P=0.000 ) , perceived knowledge ratings ( P=0.01 ) and patient satisfaction ( P=0.001 ) . There was a lower rate of medication nonadherence and health care use for the education group , but the differences were not significant . QOL indices did not change . Significant correlations were found for increased health care use in patients with poorer medication adherence ( P=0.01 ) and lower perceived health ( P=0.05 ) . CONCLUSION Formal IBD patient education improves knowledge , perceived knowledge and patient satisfaction . Further study of long-term effects may better demonstrate potential benefits for QOL , medication adherence and health care use |
11,234 | 23,338,911 | The pooled estimates of diagnostic values were more than 90 % for patient- , vessel- and segment-based assessment s. Prospect i ve ECG-triggered CCTA results in high diagnostic accuracy and image quality , with a significantly low radiation dose | The purpose of this study was to perform a systematic review of the diagnostic accuracy , image quality and radiation dose of prospect i ve electrocardiography (ECG)-triggered coronary computed tomography angiography ( CCTA ) . | The goal of our study was to compare a prospect i ve triggering ( PT ) CT technique with retrospectively gated ( RG ) CT techniques in coronary computed tomographic angiograms ( CCTA ) with respect to image quality and radiation dose . Sixty consecutive patients were enrolled . CCTAs using the RG technique were obtained with a dual- source 64-slice CT system in 40 patients , using ECG-triggered tube current modulation , with either a broad pulsing window at 30–80 % of the RR interval ( group RGb , 20 patients , heart rate > 70 bpm ) or a small pulsing window at 70 % ( group RGs , 20 patients , heart rate < 70 bpm ) . The other 20 patients underwent CCTA using the PT technique on a 128-slice CT system ( group PT , heart rate < 70 bpm ) . All images were evaluated by two observers for quality on a three-point scale , with 1 being excellent and 3 being insufficient . The effective radiation dose was calculated for each patient . The average image quality score was 1.5 ± 0.6 for PT , 1.35 ± 0.5 for RGs and 1.65 ± 0.5 for RGb . The mean effective dose for RGb was 9 ± 4 mSv , for RGs 7 ± 3 mSv and for PT 3 ± 1 mSv . This represents a 57 % dose reduction for PT compared with RGs and a 67 % dose reduction for PT compared with RGb . In conclusion , in selected patients CCTA with the PT technique offers adequate image quality with a significantly lower radiation dose compared with CCTA using RG techniques OBJECTIVE To compare , in patients with suspicion of coronary artery disease ( CAD ) and low heart rates , image quality , diagnostic performance , and radiation dose values of prospect ively and retrospectively electrocardiography (ECG)-gated dual- source computed tomography coronary angiography ( CTCA ) for the diagnosis of significant coronary stenoses . MATERIAL S AND METHODS Two-hundred consecutive patients with heart rates ≤70 bpm were retrospectively enrolled ; 100 patients undergoing prospect ively ECG-gated CTCA ( group 1 ) and 100 patients undergoing retrospectively-gated CTCA ( group 2 ) . Coronary artery segments were assessed for image quality and significant luminal diameter narrowing . Sensitivity , specificity , positive predictive values ( PPV ) , negative predictive values ( NPV ) , and accuracy of both CTCA groups were determined using conventional catheter angiography ( CCA ) as reference st and ard . Radiation dose values were calculated . RESULTS Both groups were comparable regarding gender , body weight , cardiovascular risk profile , severity of CAD , mean heart rate , heart rate variability , and Agatston score ( all p>0.05 ) . There was no significant difference in the rate of non-assessable coronary segments between group 1 ( 1.6 % , 24/1404 ) and group 2 ( 1.4 % , 19/1385 ; p=0.77 ) ; non-diagnostic image quality was significantly ( p<0.001 ) more often attributed to stair step artifacts in group 1 . Segment-based sensitivity , specificity , PPV , NPV , and accuracy were 98 % , 98 % , 88 % , 100 % , and 100 % among group 1 ; 96 % , 99 % , 90 % , 100 % , and 98 % among group 2 , respectively . Parameters of diagnostic performance were similar ( all p>0.05 ) . Mean effective radiation dose of prospect ively ECG-gated CTCA ( 2.2±0.4 mSv ) was significantly ( p<0.0001 ) smaller than that of retrospectively ECG-gated CTCA ( 8.1±0.6 mSv ) . CONCLUSION Prospect ively ECG-gated CTCA yields similar image quality , performs as accurately as retrospectively ECG-gated CTCA in patients having heart rates ≤70 bpm while being associated with a lower mean effective radiation dose BACKGROUND Prospect ively gated coronary computed tomographic angiography ( CCTA ) with dual- source CT allows substantial reduction of radiation exposure but requires prospect i ve single-phase selection and assessment of likelihood of adequate image quality . OBJECTIVE We developed and tested the model for predicting success of prospect ively gated CCTA . METHODS Retrospectively gated CCTA was acquired with dual- source CT in 162 patients . Two cardiologists assessed by consensus whether diagnostic quality images could have been obtained in a single predefined phase , 70 % of R-R interval ( 70P ) , thereby identifying patients in whom a prospect ively gated scan at 70P would have been successful . Logistic regression models were built with and without a coronary calcium scan . The obtained criteria were applied on 42 additional patients . RESULTS By logistic regression , heart rate before CCTA of > or=70 beats/min , maximal heart rate variation before CCTA of > or=10 beats/min , coronary calcium score > or= 400 U , and body mass index ( in kg/m(2 ) ) > or= 30 were independent predictors of unsuccessful prospect ively gated CCTA using 70P . Excluding coronary calcium score from the model , these same variables in addition to age > 65 years were found to be predictors of unsuccessful prospect ively gated CCTA . Applying this model to 42 additional patients , using prospect i ve gating , only 5 segments in 4 patients were nondiagnostic . Mean radiation dose for prospect ively gated CCTA was 2.2 + /- 0.8 mSv . CONCLUSION Prospect ively gated CCTA with dual- source CT can be successfully implemented with consideration of prescan heart rate , heart rate variability , body mass index , and coronary calcium score OBJECTIVES The aim of this study was to compare the diagnostic performance of multidetector computed tomography ( MDCT ) with prospect i ve electrocardiogram ( ECG ) triggering versus retrospective ECG triggering . BACKGROUND MDCT allows the noninvasive visualization of the coronary arteries . However , radiation exposure is a reason for concern . METHODS One hundred eighty consecutive patients scheduled for invasive coronary angiography were enrolled in this study . Twenty patients were excluded due to contraindications to sustain MDCT . Of the 160 remaining patients , 80 were studied with MDCT with prospect i ve ECG triggering ( Group 1 ) and 80 with a retrospective ECG triggering ( Group 2 ) . The individual radiation dose exposure was estimated . RESULTS In nonstented segments , the evaluability of Groups 1 and 2 was 96 % versus 97 % , respectively ( p = 0.05 ) , the accuracy in segment-based model was 93 % versus 96 % , respectively ( p < 0.05 ) including diagnostic segments and 91 % versus 94 % , respectively ( p < 0.01 ) including all segments , whereas the accuracy in a patient-based model was 98 % in both groups . In stented segments the evaluability in Groups 1 and 2 was 92 % versus 94 % , respectively , and the accuracy was 93 % versus 92 % , respectively , including diagnostic stented segments and 90 % versus 89 % , respectively , including all stented segments . Group 1 presented lower radiation dose compared with Group 2 ( 5.7 + /- 1.5 mSv vs. 20.5 + /- 4.3 mSv , p < 0.01 ) . CONCLUSIONS Prospect i ve ECG-triggering computed tomography allows an accurate detection of coronary stenosis , despite a slight reduction of diagnostic performance , with a low radiation dose With the advent of multislice CT more than a decade ago , multislice CT angiography has demonstrated a huge potential in the less invasive imaging of cardiovascular disease , especially in the diagnosis of coronary artery disease . The diagnostic accuracy of multislice CT angiography has been significantly augmented with the rapid technical developments ranging from the initial 4-slice , to the current 64-slice and 256 and 320-slice CT scanners . This is mainly demonstrated by the improved spatial and temporal resolution when compared to the earlier type of CT scanners . Traditionally , multislice CT angiography is acquired with retrospective ECG-gating with acquisition of volume data at the expense of increased radiation dose , since data is acquired at the entire cardiac cycle , although not all of them are used for postprocessing or reconstructions . Recently , there is an increasing trend of utilising prospect i ve ECG-gating in cardiac imaging with latest multislice CT scanners ( 64 or more slices ) with significant reduction of radiation dose when compared to retrospective ECG-gating method . However , there is some debate as to the diagnostic value of prospect i ve ECG-gating in the diagnosis of coronary artery disease , despite its attractive ability to reduce radiation dose . This article will review the performance of retrospective ECG-gating in the diagnostic value of coronary artery disease , highlight the potential applications of prospect i ve ECG-gating , and explore the future directions of multislice CT angiography in cardiac imaging PURPOSE To evaluate the effect of a small field of view ( FOV ) for step- and -shoot coronary computed tomography angiography ( CCTA ) on craniocaudal z-coverage per scan step , image quality , and radiation exposure . METHODS 53 patients underwent prospect ively ECG-gated CCTA on a 256-slice MDCT scanner using either a FOV > 250 mm ( group 1 , n = 29 ) or a FOV ≤ 250 mm ( group 2 , n = 24 ) . Craniocaudal z-coverage was determined on coronal multiplanar reformations . Image noise , signal-to-noise ratio , contrast-to-noise ratio , and qualitative image parameters were assessed . Radiation dose was estimated from the dose length product and was st and ardized for a scan range from the main pulmonary artery to the diaphragm in order to make both groups comparable . RESULTS Diagnostic image quality was achieved in 91.3 % of the coronary artery segments of group 1 and 89.9 % in group 2 ( p = 0.201 ) . There were no major differences in image noise , SNR , and CNR between both groups . A smaller FOV leads to an increase of craniocaudal coverage of a single CT scan step ( r = -0.879 ; p ≤ 0.001 ) . There was an increase of 23.8 % of the mean z-coverage per scanned subvolume in group 2 ( 59.9 mm vs. 48.8 mm ) . Radiation dose was significantly lower in group 2 ( 229 vs. 285 mGy cm , respectively ) . CONCLUSION The use of a small transverse FOV for step- and -shoot CCTA at a wide detector CT scanner leads to an increased z-coverage . 2 scan volumes are enough to image the cardiac anatomy . Radiation dose is decreased without negative impact on image quality Background — Surveillance conventional coronary angiography ( CCA ) is recommended 2 to 6 months after stent-supported left main coronary artery ( LMCA ) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis ( ISR ) , with its attendant risks . Multislice computed tomography ( MSCT ) is a promising technique for noninvasive coronary evaluation . We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA . Methods and Results — Seventy-four patients were prospect ively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA . Until August 2004 , a 16-slice scanner was used ( n=27 ) , but we switched to the 64-slice scanner after that period ( n=43 ) . Patients with initial heart rates > 65 bpm received β-blockers , which result ed in a mean periscan heart rate of 57±7 bpm . Among patients with technically adequate scans ( n=70 ) , MSCT correctly identified all patients with ISR ( 10 of 70 ) but misclassified 5 patients without ISR ( false-positives ) . Overall , the accuracy of MSCT for detection of angiographic ISR was 93 % . The sensitivity , specificity , and positive and negative predictive values were 100 % , 91 % , 67 % , and 100 % , respectively . When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch , accuracy was 98 % . When both branches of the LMCA bifurcation were stented , accuracy was 83 % . For the assessment of stent diameter and area , MSCT showed good correlation with intravascular ultrasound ( r=0.78 and 0.73 , respectively ) . An intravascular ultrasound threshold value ≥1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT . Conclusions — Current MSCT technology , in combination with optimal heart rate control , allows reliable noninvasive evaluation of selected patients after LMCA stenting . MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA We sought to determine the cut-off point of the average heart rate ( HR ) and HR differences in obtaining diagnostic image quality using prospect i ve electrocardiographically-triggered ( PT ) coronary computed tomographic angiography ( CCTA ) and to compare image quality and radiation dose for CCTA obtained with PT CCTA and retrospective electrocardiographically-gated ( RG ) CCTA . A total of 178 patients who were referred for CCTA were enrolled in the study . Two independent radiologists evaluated subjective image quality . The non-diagnostic coronary segments were 32 of 1,226 segments ( 2.6 % ) for PT CCTA and 12 of 1,346 segments ( 0.9 % ) for RG CCTA ( P < 0.001 ) . The mean image quality scores for PT CCTA and RG CCTA were 3.82 ± 0.29 and 3.93 ± 0.14 , respectively . The mean radiation dose of patients that underwent PT CCTA was 3.83 ± 0.84 mSv and RG CCTA 10.7 ± 2.70 mSv . For patients who underwent PT CCTA , image quality was inversely related to HR ( 56.5 ± 4.3 bpm ; r = 0.38 ; P < 0.001 ) and HR differences ( 2.8 ± 2.7 bpm ; r = 0.49 ; P < 0.001 ) . With the use of receiver operator characteristic analysis , a cut-off HR of 57 bpm ( 58 % sensitivity , 67 % specificity ) and HR difference of 6 bpm ( 93 % sensitivity , 46 % specificity ) were the best threshold for the prediction of diagnostic image quality . In patients with a regular , low HR , PT CCTA offers diagnostic image quality and substantially reduces effective radiation compared with the use of RG CCTA with dose modulation BACKGROUND Desirable methods for cardiac CT angiography would both reduce radiation exposure from cardiac CT angiography and preserve accuracy . OBJECTIVES We assessed image quality , radiation dose , and diagnostic accuracy of a low-dose , prospect ively gated axial cardiac CT angiography protocol for the evaluation of patients with suspected coronary artery disease ( CAD ) . METHODS Fifty consecutive patients referred for diagnostic invasive coronary angiography ( ICA ) and with a stable heart rate < 60 beats/min after beta-blocker administration were prospect ively enrolled in a single center study . Subjects underwent CT angiography with a 64-row multidetector CT scanner with a prospect ively gated axial imaging protocol . If the examination was determined to be nondiagnostic , then a retrospectively gated helical scan was performed . Two review ers independently assessed image quality and the presence of significant coronary artery stenosis ( > 50 % ) . RESULTS Prospect ively gated CT angiography was successfully performed in 46 of 50 patients . Of 794 coronary segments , 777 were determined to be of diagnostic image quality . The overall patient-based sensitivity ( 95 % CI ) , specificity , positive predictive value , negative predictive value , and accuracy for the diagnosis of significant coronary stenosis were 100 % ( 87%-100 % ) , 75 % ( 53%-90 % ) , 81 % ( 64%-93 % ) , 100 % ( 81%-100 % ) , and 88 % ( 81%-95 % ) , respectively . The mean effective radiation dose for CT angiography and ICA were 3.4 + /- 0.4 mSv and 6.9 + /- 0.8 mSv , respectively . CONCLUSIONS Cardiac CT angiography performed in a prospect ively gated axial mode with 64-row multidetector CT provides an accurate , low-dose alternative for the detection of CAD BACKGROUND / OBJECTIVES To assess the gender influence on radiation dose saving allowed by prospect i ve ECG-triggered MDCT coronary angiography ( P-MDCT-CA ) in comparison with retrospective ECG-gated MDCT-CA ( R-MDCT-CA ) . The influence of kilovoltage and body mass index on radiation dose and the impact of different parameters on image quality ( IQ ) and diagnostic confidence ( DC ) , were also determined . METHODS 64-slice MDCT-CA was performed in 176 patients : 66 R-MDCT-CA and 110 P-MDCT-CA . Effective dose was determined using ImpactDose software based on Monte Carlo method . Three point scales were used to assess IQ and DC on a segmental basis . RESULTS Patients were divided into 4 groups according with the examination performed : group A ( 90 pts , coronary tree assessment with P-MDCT-CA ) ; group B ( 55 pts , coronary tree assessment with R-MDCT-CA ) ; group C ( 20 pts , bypass grafts assessment with P-MDCT-CA ) ; and group D ( 11 pts , bypass grafts assessment with R-MDCT-CA ) . Effective dose was 68 % lower for P-MDCT-CA than R-MDCT-CA for coronary artery studies ( Gr . A=4.7 ± 1.69 mSv and Gr . B=14.9 ± 4.4 mSv ; p<0.05 ) and 63 % lower for by-pass studies . Effective dose result ed significantly higher in women than in men who underwent R-MDCT-CA ; conversely , no gender impact was observed on effective dose of P-MDCT-CA . As a result , dose saving with prospect i ve gating was more pronounced in women ( 73 % ; R-MDCT-CA:16.3 mSv , P-MDCT-CA:4.5 mSv , ) than in men ( 60 % ; R-MDCT-CA:12.8 mSv , P-MDCT-CA:4.8 mSv ) . IQ and DC of P-MDCT-CA were better or comparable than R-MDCT-CA CONCLUSIONS : P-MDCT-CA provides at least comparable IQ and DC than R-MDCT-CA with significant dose saving . This study highlights the important advantage offered by using P-MDCT-CA in female patients PURPOSE To assess coronary artery image quality and patient radiation exposure in patients who underwent clinical ly indicated 256-slice CTA . METHODS Consecutive patients ( n=193 ) underwent 256-slice CTA , using ( 1 ) retrospective gating without radiation dose modulation , ( 2 ) retrospective gating with radiation dose modulation and ( 3 ) prospect i ve gating . Image quality was determined by consensus of two experienced observers using a 5- grade scale . The effective dose was calculated . RESULTS In all patients , CTA was performed without adverse events . Retrospective CTA was assessed in 39 patients with and 39 without dose modulation , while 115 patients underwent prospect i ve CTA . Heart rate was related to image quality with all protocol s ( r=0.46 , p<0.001 ) . Up to a heart rate of 75 bpm no significant difference in overall image quality was observed for all three protocol s , while no significant differences could be observed between retrospective CTA with and without dose modulation for any segments or heart rates . Prospect i ve and retrospective CTA with dose modulation showed radiation savings of ∼75 % and ∼30 % , respectively compared to retrospective CTA without dose modulation ( p<0.001 ) . CONCLUSIONS In patients with heart rates up to 75 bpm prospect i ve CTA should be the first choice acquisition protocol . For heart rates > 75 bpm , retrospective CTA with dose modulation should be considered OBJECTIVE The purpose of this study was to compare the patient radiation dose and coronary artery image quality of long-z-axis whole-chest 64-MDCT performed with retrospective ECG gating with those of CT performed with prospect i ve ECG triggering in the evaluation of emergency department patients with nonspecific chest pain . SUBJECTS AND METHODS Consecutively registered emergency department patients with nonspecific low-to-moderate-risk chest pain underwent whole-chest CT with retrospective gating ( n = 41 ) or prospect i ve triggering ( n = 31 ) . Effective patient radiation doses were estimated and compared by use of unpaired Student 's t tests . Two review ers independently scored the quality of images of the coronary arteries , and the scores were compared by use of ordinal logistic regression . RESULTS Age , heart rate , body mass index , and z-axis coverage were not statistically different between the two groups . For retrospective gating , the mean effective radiation dose was 31.8 + /- 5.1 mSv ; for prospect i ve triggering , the mean effective radiation dose was 9.2 + /- 2.2 mSv ( prospect i ve triggering 71 % lower , p < 0.001 ) . Two of 512 segments imaged with retrospective gating were nonevaluable ( 0.4 % ) , and two of 394 segments imaged with prospect i ve triggering were nonevaluable ( 0.5 % ) . Prospect ively triggered images were 2.2 ( 95 % CI , 1.1 - 4.5 ) times as likely as retrospectively gated images to receive a high image quality score for each segment after adjustment for segment differences ( p < 0.05 ) . CONCLUSION For long-z-axis whole-chest 64-MDCT of emergency department patients with nonspecific chest pain , use of prospect i ve ECG triggering may result in substantially lower patient radiation doses and better coronary artery image quality than is achieved with retrospective ECG gating A prospect i ve , electrocardiographically gated technique was recently adapted for use with coronary and cardiac multidetector row CT studies . The most widely available form of prospect i ve gating uses " step- and -shoot " axial data acquisition , an incrementally moving table , adaptive electrocardiographic triggering , an improved image reconstruction algorithm , and multiphase reconstruction capability . Studies have shown a 77%-87 % effective radiation dose reduction compared with retrospective gating and equal to significantly improved image quality . Comparison with conventional angiography has proven it to be as accurate as retrospective gating for coronary stenosis detection . The technique is not applicable to all patients because there are some restrictions for clinical use , including a limited number of reconstructed phases and a maximum scan heart rate of 68 - 75 beats/min . However , with careful patient selection and effective heart rate control , prospect i ve gating can be used in a high percentage of cardiac CT examinations . This article review s the scanning and patient selection protocol s for prospect i ve gating and discusses how it may be used in clinical practice OBJECTIVES The aim of this study was to evaluate radiation dose and coronary assessability of a prospect i ve electrocardiogram (ECG)-gated scan by 64-slice multidetector ( row ) computed tomography (MDCT)-coronary angiography ( CA ) compared with a retrospective ECG-gated helical scan . BACKGROUND The 64-slice MDCT-CA has been widely used ; however , a high radiation dose by 64-slice MDCT-CA has been reported . Prospect i ve ECG-gated scan using " step- and -shoot " protocol can reduce radiation exposure effectively . METHODS MDCT-CA was performed in 229 consecutive patients . Fifty-six patients were excluded because of higher heart rates of > 65 beats/min ; of patients with heart rates < or=65 beats/min , 97 were analyzed by helical scan with tube current modulation and 76 were analyzed by prospect i ve gating . Coronary assessability and diagnostic accuracy were investigated in comparison with selective CA as the gold st and ard . Radiation doses were evaluated in both protocol s. RESULTS Coronary assessability of helical scan was 95.5 % ( 1,303 of 1,364 segments ) , while that of prospect i ve gating was 96.6 % ( 1,053 of 1,089 segments ) , showing similar coronary assessability ( p = 0.14 ) . Sensitivity and specificity for coronary obstructive and occlusive lesions in the assessable segments were 97.0 % ( 162 of 167 ) and 97.6 % ( 1,109 of 1,136 ) by helical scan , while those of prospect i ve gating were 96.4 % ( 81 of 84 , p = 0.84 ) and 98.5 % ( 955 of 969 , p = 0.12 ) , respectively . Effective doses of helical scan and prospect i ve gating were 21.1 + /- 6.7 mSv and 4.3 + /- 1.3 mSv , respectively ( p < 0.0001 ) , showing that prospect i ve gating decreased radiation dose by 79 % compared with that of helical scan . CONCLUSIONS MDCT-CA by prospect i ve gating showed equivalent coronary assessability and diagnostic accuracy with decreased radiation dose in comparison with a retrospective ECG-gated helical scan with tube current modulation PURPOSE To show that prospect i ve electrocardiographically (ECG)-triggered coronary computed tomographic ( CT ) angiography ( hereafter , prospect i ve CT angiography ) is at least as effective as retrospective ECG-gated coronary CT angiography ( hereafter , retrospective CT angiography ) . MATERIAL S AND METHODS Institutional review committee approval and informed consent were obtained . Sixty patients with heart rates of less than 75 beats per minute who were referred for coronary CT angiography were enrolled . Both prospect i ve and retrospective CT angiography were performed with a 64-detector scanner . Data acquisition times were recorded . Two independent cardiac radiologists evaluated subjective image quality ( 1 , excellent ; 4 , poor ) and severity of stenosis ( 0 % occlusion , 1%-49 % occlusion , 50%-75 % occlusion , and > 75 % occlusion ) with the 17-segment American Heart Association classification model . Discrepancies were settled by consensus . Effective radiation doses of prospect i ve and retrospective CT angiography were calculated with volume CT dose index . Data regarding acquisition time and radiation exposure for prospect i ve and retrospective CT angiography were compared . The Student t test was performed , and kappa statistics were calculated . RESULTS Mean data acquisition time of prospect i ve CT angiography was shorter than that of retrospective CT angiography ( 5.6 seconds + /- 1.1 [ st and ard deviation ] vs 6.7 seconds + /- 1.1 , respectively ; P < .01 ) . Consensus-determined image quality in coronary artery branches was similar between prospect i ve CT angiography and retrospective CT angiography ( 1.15 vs 1.13 , respectively ; P = .992 ) . Excellent agreement between prospect i ve CT angiography and retrospective CT angiography was observed in the detection of significant ( > or=50 % occlusion ) coronary artery stenoses per segment ( kappa = 0.882 ) and in the grading of stenoses per patient ( kappa = 0.829 ) . Calculated effective dose with prospect i ve CT angiography was 79 % lower than that with retrospective CT angiography ( 4.1 mSv + /- 1.8 vs 20.0 mSv + /- 3.5 , respectively ; P < .001 ) . CONCLUSION Prospect i ve CT angiography can reduce radiation dose below that of retrospective CT angiography with dose modulation , while maintaining image quality and the ability to assess luminal obstructions in patients with heart rates of less than 75 beats per minute Helical prospect i ve ECG-gating ( pECG ) may reduce radiation dose while maintaining the advantages of helical image acquisition for coronary computed tomography angiography ( CCTA ) . Aim of this study was to evaluate helical pECG – gating in CCTA in regards to radiation dose and image quality . 86 patients undergoing 64-multislice CCTA were enrolled . pECG-gating was performed in patients with regular heart rates ( HR ) < 65 bpm ; with the gating window set at 70–85 % of the cardiac cycle . All patients received oral and some received additional IV beta-blockers to achieve HR < 65 bpm . In patients with higher or irregular HR , or for functional evaluation , retrospective ECG-gating ( rECG ) was performed . The average X-ray dose was estimated from the dose length product . Each arterial segment ( modified AHA/ACC 17-segment-model ) was evaluated on a 4-point image quality scale ( 4 = excellent ; 3 = good , mild artefact ; 2 = acceptable , some artefact , 1 = uninterpretable ) . pECG-gating was applied in 57 patients , rECG-gating in 29 patients . There was no difference in age , gender , body mass index , scan length or tube output setting s between both groups . HR in the pECG-group was 54.7 bpm ( range , 43–64 ) . The effective radiation dose was significantly lower for patients scanned with pECG-gating with mean 6.9 mSv ± 1.9 ( range , 2.9–10.7 ) compared to rECG with 16.9 mSv ± 4.1 ( P < 0.001 ) , result ing in a mean dose reduction of 59.2 % . For pECG-gating , out of 969 coronary segments , 99.3 % were interpretable . Image quality was excellent in 90.2 % , good in 7.8 % , acceptable in 1.3 % and non-interpretable in 0.7 % ( n = 7 segments ) . For patients with steady heart rates < 65 bpm , helical prospect i ve ECG-gating can significantly lower the radiation dose while maintaining high image quality Purpose To compare image quality and effective radiation dose for prospect ively gated axial CT coronary angiography on 64- and 256-slice CT . Methods The patient cohort consisted of 80 consecutive patients undergoing imaging with 256-slice CT and 80 patients with 64-slice CT . The two patient groups were demographically matched according to age , gender , body mass index and heart rate . For both groups , two observers independently assessed image quality for all coronary segments on a five-point ordinal scale . The two groups were compared with regard to image quality and effective radiation dose . Image quality scores less than 3 were considered non-diagnostic . Results Mean effective radiation dose did not significantly differ between the two groups ( 3.4 ± 0.8 mSv in both groups ; p > 0.1 ) . Vessel-based image quality was significantly better in patients undergoing 256-slice CT compared with those undergoing 64-slice CT ( p < 0.001 ) . The proportion of assessable coronary segments significantly increased from 95.6 % in the 64-slice group to 98.9 % in the 256-slice group ( p < 0.05 ) . Conclusion Prospect ively gated axial CT coronary angiography performed on 256-slice CT provides significantly improved and more stable image quality at an equivalent effective radiation dose compared with 64-slice CT OBJECTIVE new technologies for computed tomography coronary arteries imaging aim to reduce the radiation dose whilst maintaining image quality . The purpose of our study was to compare radiation dose and image quality parameters of Coronary Computed Tomography Angiography ( CCTA ) performed with retrospective 64-MDCT and prospect i ve 128-MDCT . PATIENTS AND METHODS a series of 77 consecutive patients were first r and omised to either retrospective 64-MDCT ( n=37 ) or prospect i ve 128-MDCT ( n=40 ) for CCTA . All patients in the retrospective 64-MDCT group were scanned with tube current modulation as strategy for reduction dose . Data regarding acquisition time and radiation dose were recorded . Two blinded radiologists independently assessed image quality of all coronary segments by using a four-point scale ( 1 , excellent ; 4 , poor ) . Discrepancies were settled by consensus . RESULTS No significant differences were found regarding sex , age , body weight and heart rate . CTTA effective radiation dose was 2.1 ± 0.9 vs. 8.2 ± 4mSv in prospect i ve and retrospective ECG-gating MDCT groups , respectively . Mean image quality score was 2.2 ± 0.9 for prospect i ve 128-MDCT group and 1.4 ± 0.7 points for retrospective 64-MDCT representing a mean difference of 0.8 points ( CI : 0.9 to 0.7 ) . CONCLUSION in selected patients , CCTA using a 128-MDCT with prospect i ve ECG-gating provides higher image quality with significant lower radiation dose when compared to 64-MDCT using retrospective ECG-gating PURPOSE To explore feasibility of dual- source CT ( DS-CT ) prospect i ve ECG-gated coronary angiography in patients with heart rate ( HR ) higher than 70beat per minute ( bpm ) , and evaluate image quality and radiation dose with comparison to retrospective ECG-gated spiral scan . MATERIAL S AND METHODS One hundred patients who underwent DS-CT coronary angiography ( DS-CTCA ) with mean HR higher than 70bpm but below 110bpm were enrolled in the study , 50 were scanned by adaptive sequential scan and another 50 were analyzed by retrospectively gated CT scan . The imaging quality of coronary artery segments in the two groups was evaluated using a four-point grading scale by two independent review ers . Patient radiation dose was calculated by multiplying dose length product by conversion coefficient of 0.017 . RESULTS There was no significant difference between the two groups for mean HR ( p=0.305 ) , HR variability ( p=0.103 ) , body mass index ( p=0.472 ) , and scan length ( p=0.208 ) . There was good agreement for image quality scoring between the two review ers ( Kappa=0.72 ) . Coronary evaluability of adaptive sequential scan was 99.7 % ( 608 of 610 segments ) , while that of retrospective gated scan was 98.7 % ( 614 of 622 segments ) , showing similar coronary evaluability ( p=0.061 ) . Effective doses of adaptive sequential scan and retrospective gated scan were 5.1±1.6 and 11.8±4.5mSv , respectively ( p<0.001 ) , showing that adaptive sequential scan reduced radiation dose by 57 % compared with that of retrospective gated scan . CONCLUSIONS In patients with 70 - 110bpm HR , DS-CTCA adaptive sequential scan shows similar image quality as retrospective ECG-gated spiral scan with 57 % reduction of radiation dose Objective To compare the diagnostic accuracy and radiation doses of two low-dose protocol s for coronary artery imaging with second-generation , dual- source CT in comparison with catheter angiography ( CA ) . Design , setting and patients Prospect i ve , single-centre study conducted in a referral centre enrolling 100 patients with low-to-intermediate risk and suspicion of coronary artery disease . All patients underwent contrast-enhanced , 128-slice , dual- source CT coronary angiography and CA . Patients were r and omly assigned to two different low-dose CT protocol s ( each 100 kV/320 mA ) : in group A ( n=50 ) , CT was performed using the prospect ively electrocardiography (ECG)-gated step- and -shoot ( SAS ) mode ; in group B ( n=50 ) , CT was performed using the prospect ively ECG-gated high-pitch mode ( pitch 3.4 ) . The image quality and presence or absence of significant coronary stenosis in all coronary segments were evaluated by two blinded and independent observers . CA served as the st and ard of reference . Results Sixty-one significant stenoses were found in group A , and 69 in group B. There was no significant difference in age ( group A , 62±8yrs ; group B , 63±8yrs ; p=0.72 ) , body mass index ( group A , 26.4±3.1kg/m2 ; group B , 25.9±2.8kg/m2 ; p=0.41 ) and heart rate ( HR ) ( group A , 58±8bpm ; group B , 56±10bpm ; p=0.66 ) between the groups . Diagnostic image quality was obtained in 98.6 % ( 651/660 ) of segments in group A and in 98.9 % ( 642/649 ) in group B , with no significant differences between groups . Sensitivity , specificity and positive and negative predictive values were 94 % , 91 % , 85 % and 97 % per-patient in group A , and 93 % , 94 % , 89 % and 97 % per-patient in group B ( no significant differences ) . The effective radiation dose in group B ( 0.9±0.1 mSv ) was significantly ( p<0.01 ) lower than that in group A ( 1.4±0.4 mSv ) . Conclusions Both the high-pitch and the SAS mode for low-dose CT coronary angiography provide high accuracy for the assessment of significant coronary stenoses , while the high-pitch mode further significantly lowers the radiation dose Computed tomography ( CT ) coronary angiography has been widely used since the introduction of 64-slice scanners and dual- source CT technology , but high radiation doses have been reported . Prospect i ve ECG-gating using a ' step- and -shoot ' axial scanning protocol has been shown to reduce radiation exposure effectively while maintaining diagnostic accuracy . 256-slice scanners with 80 mm detector coverage have been currently introduced into practice , but their impact on radiation exposure has not been adequately studied . The aim of this study was to assess radiation doses associated with CT coronary angiography using a 256-slice CT scanner . Radiation doses were estimated for 25 patients scanned with either prospect i ve or retrospective ECG-gating . Image quality was assessed objective ly in terms of mean CT attenuation at selected regions of interest on axial coronary images and subjectively by coronary segment quality scoring . It was found that radiation doses associated with prospect i ve ECG-gating were significantly lower than retrospective ECG-gating ( 3.2 + /- 0.6 mSv versus 13.4 + /- 2.7 mSv ) . Consequently , the radiogenic fatal cancer risk for the patient is much lower with prospect i ve gating ( 0.0176 % versus 0.0737 % ) . No statistically significant differences in image quality were observed between the two scanning protocol s for both objective and subjective quality assessment s. Therefore , prospect i ve ECG-gating using a ' step- and -shoot ' protocol that covers the cardiac anatomy in two axial acquisitions effectively reduces radiation doses in 256-slice CT coronary angiography without compromising image quality To prospect ively evaluate image quality parameters , contrast volume and radiation dose at the 100-kilovolt ( kV ) setting during coronary computed tomographic angiography ( CCTA ) on a 320-row computed tomography scanner . We enrolled 107 consecutive patients with a heart rate < 65 beats per minute ( bpm ) undergoing prospect i ve electrocardiogram (ECG)-triggered CCTA . Forty patients with a body mass index ( BMI ) < 25 kg/m2 were scanned using 100-kV tube voltage setting s , while 67 patients were scanned using 120-kV protocol s. Image quality was assessed by two readers unaware of patient information and scan parameters . Attenuation in the aorta and perivascular fat tissue and image noise were measured . Contrast-to-noise ratios ( CNRs ) and contrast material volumes were calculated . The effective radiation doses were estimated using a chest conversion coefficient ( 0.017 ) . Diagnostic image quality was achieved in 98.2 % of coronary segments with 100-kV CCTA and 98.6 % of coronary segments with 120-kV CCTA , with no significant differences in image quality scores for each coronary segment . Vessel attenuation , image noise , and CNR were not significantly different between the 100- and 120-kV protocol s. Mean contrast injection rate and mean material volume were significantly lower for the 100-kV CCTA ( 4.35 ± 0.28 ml/s and 53.13 ± 3.77 ml , respectively ) than for the 120-kV CCTA ( 5.16 ± 0.21 ml/s and 62.40 ± 3.66 ml respectively ; P < 0.001 ) . The effective radiation dose was 2.12 ± 0.19 mSv for 100-kV CCTA , a reduction of 54 % compared to 4.61 ± 0.82 mSv for 120-kV CCTA . A 100-kV CCTA can be implemented in patients with a BMI < 25 kg/m2 . The 100-kV setting allows significant reductions in contrast material volume and effective radiation dose while maintaining adequate diagnostic image quality BACKGROUND The 320-row multidetector CT ( MDCT ) provides the capability for prospect i ve electrocardiogram-gated cardiac CT angiography . OBJECTIVE We assessed the effective radiation doses of MDCT with a 320-row detector volume scanner . METHODS Two hundred patients underwent clinical ly directed cardiac scanning ( 100 kVp , n=9 or 120 kVp , n=191 ; range , 300 - 580 mA ) . Effective radiation dose ( in mSv ) was estimated from extended dose-length product . For heart rates ( HRs ) < 65 beats/min , exposure phase was 65 % up to the end of R wave of the cardiac cycle , using a one-heart beat acquisition and half-scan reconstruction . HRs from 66 to 79 beats/min and > or = 80 beats/min were scanned with either 2- or 3-heart beat acquisitions , respectively . Patients with arrhythmias were not excluded . RESULTS The mean effective dose was 5.7+/-1.7 mSv ( range , 1.6 - 11.1 mSv ) for 151 patients ( 75 % ) scanned with a one-heart beat acquisition . Qualitative image quality was assessed to be in good to excellent range , and mottle image quality was in low-to-medium mottle range . For patients scanned with 2- or 3-heart beat acquisition , radiation dose was higher with mean exposures of 13.0+/-3.3 mSv and 19.5+/-5.3 mSv , respectively . CONCLUSIONS Low effective radiation dose with acceptable image quality on 320-row MDCT can be achieved with one-heart beat scan acquisition when HR is < 65 beats/min . Further reduction in dose can likely also be achieved by modification of the prospect ive-gated imaging parameters This study was conducted on a human anthropomorphic phantom to investigate the effective dose and entrance skin dose ( ESD ) in selected radiosensitive organs through invasive and computed tomography ( CT ) coronary angiography procedures using different dose-saving techniques . The effective dose was calculated as 2.49 , 3.35 and 9.62 mSv , respectively , corresponding to three coronary CT angiography protocol s , including prospect i ve ECG gating and retrospective ECG gating with and without tube current modulation . In comparison , the effective dose was calculated as 7.26 , 6.35 , 5.58 and 4.71 mSv at four different magnifications acquired with invasive coronary angiography . The highest ESD was measured in the breast during the coronary CT angiography and in the thyroid gl and during invasive coronary angiography . Although invasive coronary angiography produces lower radiation dose than coronary CT angiography , application of modified techniques in both CT and invasive coronary angiography is recommended in clinical practice for radiation dose reduction AIM To evaluate image quality and radiation dose for 128-detector prospect i ve electrocardiogram (ECG)-gated computed tomography coronary angiography ( CTCA ) compared with a low-dose retrospective ECG-gated imaging protocol . MATERIAL S AND METHODS Thirty-one and 47 patients suspected of having coronary artery disease were enrolled into groups examined using prospect i ve and low-dose retrospective ECG-gated CT protocol s respectively . All examinations were performed on a 128-detector CT system ( Definition AS , Siemens Healthcare , Forchheim , Germany ) . Prospect i ve CTCA was performed using following parameters : tube voltage 100 kV ; tube current 205 mAs ; centre of acquisition window 70 % of the RR interval . The tube current for low-dose retrospective ECG-gated CTCA was full dose during 40 - 70 % of the RR interval and partial dose for the rest of RR interval . The pitch varied between 0.2 and 0.5 depending on heart rate and patient size . Image quality of coronary arteries was evaluated using a four-point grading scale . The signal-to-noise ratios ( SNRs ) of enhanced arteries and myocardium were also measured , corresponding contrast-to-noise ratios ( CNRs ) were calculated , and the radiation doses received were recorded . RESULTS There was a significant difference in the image quality scores between the retrospective and prospect i ve gating protocol s ( Chi-square=15.331 , p=0.009 ) . There was no significant difference between the SNRs of the contrasted artery and myocardium in these two groups , but the CNRs were increased in the prospect i ve group . The mean radiation dose of prospect i ve gating group was 2.71+/-0.67 mSv ( range , 1.67 - 3.59 mSv ) , which was significantly lower than that of the retrospective group ( p<0.001 ) . CONCLUSION Prospect i ve CT angiography can achieve lower radiation dose than that of low-dose retrospective CT angiography , with preserved image quality The American College of Cardiology ( ACC ) and the American Heart Association ( AHA ) support their members ’ goal to improve the prevention and care of cardiovascular diseases through professional education , research , development of guidelines and st and ards , and by fostering policy that supports optimal patient outcomes . The ACC and AHA recognize the importance of the use of clinical data st and ards for patient management , to assess outcomes , and conduct research , and the importance of defining the processes and outcomes of clinical care , whether in r and omized trials , observational studies , registries , or quality improvement initiatives . Hence , clinical data st and ards strive to define and st and ardize data relevant to clinical topics in cardiology , with the primary goal of assisting data collection by providing a platform The purpose of this study was to evaluate and compare the diagnostic accuracy and radiation dose of dual- source computed tomographic ( DSCT ) coronary angiography for assessment of coronary artery disease using prospect i ve electrocardiographic triggering and retrospective electrocardiographically ( ECG ) gated spiral scans . One hundred sixteen patients who had undergone dual- source computed tomography and conventional coronary angiography were enrolled in this study . Fifty-four patients were scanned using retrospective ECG-gated protocol s ( group 1 ) and 62 patients using prospect i ve ECG-triggered protocol s ( group 2 ) . Diagnostic accuracy , image quality , and effective dose were compared between groups 1 and 2 . Conventional coronary angiography was used as the reference st and ard . In total 1,709 ( 98.2 % ) coronary segments in the 116 patients were assessable with adequate image quality . Sensitivities and specificities of diagnosing coronary heart disease ( ≥50 % stenosis ) in a patient-based analysis of DSCT data were 93.3 % and 88.9 % in group 1 and 96.4 % and 85.7 % in group 2 , respectively ( p=0.973 and 0.761 ) . In vessel-based analysis , sensitivities and specificities were 77.4 % and 94.1 % in group 1 and 79.6 % and 92.3 % in group 2 ( p=0.983 and 0.985 ) . Overall averaged image quality scores ( using 1- to 4-point scale ) in groups 1 and 2 were 3.3 ± 0.4 and 3.5 ± 0.9 , respectively ( p=0.268 ) . Prevalence of good ( score 3.0 ) and excellent ( score 4.0 ) image qualities of coronary vessels were 95.4 % in group 1 and 92.4 % in group 2 ( p = 0.861 ) . Effective doses were 8.82 ± 3.50 mSv ( range 3.92 to 15.36 ) in group 1 and 2.95 ± 1.39 mSv ( range 0.99 to 6.06 ) in group 2 ( p<0.001 ) . In conclusion , DSCT prospect i ve ECG-triggered coronary angiography has equivalent image quality and diagnostic value compared to that of retrospective ECG-gated scans . Radiation dose was significantly decreased using prospect i ve electrocardiographic triggering PURPOSE To compare image quality and patient radiation dose in a group of patients who underwent 320-detector computed tomography coronary angiography performed with prospect i ve electrocardiogram ( ECG ) gating with image quality and radiation dose in a group of patients matched for clinical features who underwent 320-detector computed tomographic ( CT ) coronary angiography performed with retrospective ECG gating . MATERIAL S AND METHODS This study was approved by our institutional human research committee . All patients had clinical indications for coronary computed tomography angiography ( CTA ) . Two independent review ers separately scored coronary artery segment image quality for 480 cardiac CT studies in prospect i ve group and retrospective group ( 240 in each group ) . Review er variability was calculated . Estimated effective radiation dose was compared for prospect i ve versus retrospective ECG gating . RESULTS The two groups matched well for clinical characteristics and CT parameters . There was good agreement for coronary artery segment image quality scores between the independent review ers ( k=0.73 ) . Of the 6408 coronary artery segments scored , there were no coronary artery segments that could not be evaluated in each group . Image quality scores were not significantly different ( P>.05 ) . Mean patient radiation dose was 76.50 % lower for prospect i ve gating ( 4.2 mSv ) than for retrospective gating ( 18.1 mSv ) ( P<.01 ) . CONCLUSION Use of 320-detector CT coronary angiography performed with prospect i ve ECG gating has similar subjective image quality scores but 76.50 % lower patient radiation dose when compared with use of retrospective ECG gating OBJECTIVES We sought to assess the feasibility of prospect i ve electrocardiogram triggering for achieving low-dose computed tomography coronary angiography ( CTCA ) in a large population . BACKGROUND Prospect i ve electrocardiogram triggering dramatically reduces radiation exposure for CTCA but requires heart rate ( HR ) control to obtain diagnostic image quality . Its feasibility in daily clinical routine has therefore remained to be eluci date d. METHODS We evaluated 612 patients consecutively referred for CTCA by 64-slice computed tomography . Intravenous metoprolol ( 2 to 30 mg ) was administered if necessary to achieve a target HR below 65 beats/min . Image quality was assessed on a semiquantitative 4-point scale for each coronary segment . RESULTS Forty-six ( 7.5 % ) patients were deemed ineligible due to irregular heart rhythm ( n = 19 ) , insufficient response to metoprolol ( n = 21 ) , renal insufficiency ( n = 3 ) , or inability to follow breath-hold comm and s ( n = 3 ) . Mean effective radiation dose was 1.8 ± 0.6 mSv with a diagnostic image quality in 96.2 % of segments . Finally , low-dose CTCA allowed a firm diagnosis with regard to the presence or absence of coronary artery disease in 527 ( 86.1 % ) patients . Intravenous metoprolol to achieve an HR below 65 beats/min was used in 64.4 % of patients . Incidence of nondiagnostic segments was inversely related to HR ( r = -0.809 , p < 0.001 ) . Below an HR cutoff of 62 beats/min , only 1.2 % of coronary segments were nondiagnostic . CONCLUSIONS Low-dose CTCA by electrocardiogram triggering is feasible in the vast majority of an every-day population . However , HR control is crucial , as an HR below 62 beats/min favors diagnostic image quality |
11,235 | 23,126,424 | Recent r and omized trials have demonstrated that laparoscopic gastric and colorectal cancer resection are safe and oncologically correct procedures .
However , evidence -based medicine has failed to show major advantages in SILS , and the disadvantage of robotic surgery is the high costs related to purchase and maintenance of technology . | Laparoscopic surgery has been widely adopted and new technical innovation , procedures and evidence based knowledge are persistently emerging .
This review documents recent major advancements in laparoscopic surgery .
Laparoscopic cholecystectomy is the most frequently performed procedure , followed by laparoscopic bariatric surgery .
Although bile duct injuries are relatively uncommon ( 0.15%-0.6 % ) , intraoperative cholangiography still plays a role in reducing the cost of litigation .
Laparoscopic bariatric surgery is the most commonly performed laparoscopic gastrointestinal surgery in the USA , and laparoscopic Nissen fundoplication is the treatment of choice for intractable gastroesophageal reflux disease .
Laparoscopic surgery has also been widely developed in hepatic , pancreatic , gynecological and urological surgery .
Recently , SILS and robotic surgery have penetrated all specialties of abdominal surgery .
Laparoscopic surgery has become well developed in recent decades and is the choice of treatment in abdominal surgery . | Background : Hypothermia during and after major abdominal surgery decreases host defenses , increases the incidence of coagulopathy and may alter blood pressure , cardiac contractility and myocardial stability . Methods : We design ed a prospect i ve r and omized study to compare the benefits of a forced air warming system with warm blanket treatments in minimizing the effects of hypothermia on 64 morbidly obese patients undergoing Roux-en-Y gastric bypass . Results : Patients in the forced air warming group ( n = 32 ) had significantly higher perioperative body core temperature , lower central venous pressure and blood pressure readings , lower incidence of shivering , less blood loss intraoperatively and achieved a higher post anesthesia Aldrete Score than those patients in the warmed blanket group ( n = 32 ) . Conclusion : The forced air warming system is safe , cost effective and beneficial in minimizing the undesirable consequences of hypothermia in morbidly obese patients undergoing Roux-en-Y gastric bypass BACKGROUND The magnitude of the systemic stress response is proportional to the degree of operative trauma . We hypothesized that laparoscopic gastric bypass ( GBP ) is associated with reduced operative trauma compared with open GBP , result ing in a lower systemic stress response . STUDY DESIGN Forty-eight patients with a body mass index of 40 to 60 were r and omly assigned to laparoscopic ( n = 26 ) or open ( n = 22 ) GBP Blood sample s were measured at baseline and at 1 , 24 , 48 , and 72 hours postoperatively . Metabolic ( insulin , glucose , epinephrine , norepinephrine , dopamine , ACTH , cortisol ) , acute phase ( C-reactive protein ) , and cytokine ( interleukin [IL]-6 , IL-8 , tumor necrosis factor [TNF]-alpha ) responses were measured . Catabolic response was also measured by calculating the nitrogen balance at 24 and 48 hours postoperatively . RESULTS The two groups of patients were similar in terms of age , gender , and preoperative body mass index . The mean operative time was longer for laparoscopic GBP than for open GBP ( 229 + /- 50 versus 207 43 minutes ) . After laparoscopic and open GBP , plasma concentrations of insulin , glucose , epinephrine , dopamine , and cortisol increased ; IL-8 and TNF-alpha remained unchanged ; and negative nitrogen balances occurred at 24 and 48 hours . There was no significant difference in these parameters between groups . Concentrations of norepinephrine , ACTH , C-reactive protein , and IL-6 levels also increased , but these levels were significantly lower after laparoscopic GBP than after open GBP ( p < 0.05 ) . CONCLUSIONS Systemic stress response after laparoscopic GBP is similar to that after open GBP , except that concentrations of norepinephrine , ACTH , C-reactive protein , and IL-6 are lower after laparoscopic than after open GBP . These findings may suggest a lower degree of operative injury after laparoscopic GBP The benefits of laparoscopic appendectomy appear to be controversial . Since 1994 , several abdominal procedures have been completed by using the needlescopic technique , but there appear to be no prospect i ve studies to demonstrate the perceived benefits of needlescopic appendectomy . The authors compared open , laparoscopic , and needlescopic appendectomy in a r and omized fashion with regard to duration of surgery , length of hospitalization , analgesic dosage , and surgery-associated complications . From March to July 1998 , 75 patients admitted at the emergency station of the authors ' hospital with a final diagnosis of acute appendicitis without tumor formation were r and omized to receive one of the three treatment categories : open ( OA ) , laparoscopic ( LA ) , and needlescopic ( nLA ) appendectomy . Laparoscopic and needlescopic appendectomy were performed by using a three-port technique , although the size of the trocar used varied . There were 26 patients in the OA group , 23 in the LA group , and 26 in the nLA group . The mean operation duration s for the OA , LA , and nLA groups were 55.4 ± 28.0 minutes , 69.1 ± 48.8 minutes , and 62.3 ± 26.3 minutes , respectively , and these were not significantly different from one another . The mean number of the analgesic doses ( Pethidine 1 mg/kg ) required was 1.3 ± 1.2 mg/kg , 0.5 ± 0.8 mg/kg , and 0.2 ± 0.6 mg/kg , respectively . Significant differences were noted when comparing the OA with the LA or nLA groups ( OA vs. LA , P = 0.02 ; OA vs. nLA , P = 0.0002 ; LA vs. nLA , P = 0.06 ) . The mean oral intake duration s were 32.2 ± 16.9 hours , 21.0 ± 14.6 hours , and 20.8 ± 16.4 hours , respectively , after surgery for the OA , LA , and nLA groups , and the between-group differences were statistically significant for the OA versus LA group ( P = 0.004 ) and for the OA versus nLA group ( P = 0.003 ) . The mean duration s of hospitalization for the OA , LA , and nLA groups were 3.6 ±1.8 days , 2.8 ± 1.4 days , and 2.4 ± 0.9 days , and difference was detected between the OA and the nLA groups ( P = 0.02 ) . The OA group rendered a greater wound-complication rate and ileus than did the other two groups , but the differences were not detected between the three categories ( P = 0.065 , 0.6935 ) . The result of the current study confirmed that the nLA procedure is a feasible and safe one . The nLA procedure provided substantial advantages over the OA procedure in the context s of diminished postoperative pain and shorter hospital stay without significant increases in postoperative complication rate or surgical time HYPOTHESIS Laparoscopic gastric bypass ( GBP ) induces a postoperative hypercoagulable state that is similar or reduced compared with open GBP . SETTING University hospital . PATIENTS Between May 1999 and June 2000 , 70 patients were r and omly assigned to laparoscopic ( n = 36 ) or open ( n = 34 ) GBP . Deep venous thrombosis ( DVT ) prophylaxis consisted of antiembolism stockings and sequential pneumatic compression devices . MAIN OUTCOME MEASURES Plasminogen , thrombin-antithrombin complex ( TAT ) , prothrombin fragment 1.2 ( F1.2 ) , fibrinogen , D-dimer , antithrombin III ( AT ) , and protein C levels were measured at baseline and at 1 , 24 , 48 , and 72 hours postoperatively . A venous duplex examination of both lower extremities was performed preoperatively and between the third and fifth day postoperatively . RESULTS The 2 groups were similar in age , weight , and body mass index . Plasminogen levels decreased , and TAT , F1.2 , and fibrinogen levels increased after laparoscopic and open GBP . There was no significant difference in these levels between groups . D-dimer levels increased in both groups , but the levels were significantly higher after open GBP than after laparoscopic GBP ( P<.01 ) . Antithrombin III and protein C levels decreased in both groups . The reduction of AT ( at 1 hour ) and protein C ( at 72 hours ) was significantly less after laparoscopic GBP than after open GBP ( P<.05 ) . Postoperative venous duplex examination revealed DVT in 1 ( 2.9 % ) of 34 patients after open GBP but in none of 36 patients after laparoscopic GBP . One patient developed pulmonary embolism after open GBP . CONCLUSIONS Laparoscopic GBP induces a hypercoagulable state similar to that of open GBP . Our findings suggest that DVT prophylaxis should be used during laparoscopic GBP as in open GBP BACKGROUND Impairment of pulmonary function is common after upper abdominal operations . The purpose of this study was to compare postoperative pulmonary function and analgesic requirements in patients undergoing either laparoscopic or open Roux-en-Y gastric bypass ( GBP ) . STUDY DESIGN Seventy patients with a body mass index of 40 to 60 kg/m2 were r and omly assigned to undergo laparoscopic ( n = 36 ) or open ( n = 34 ) GBP . The two groups were similar in age , gender , body mass index , pulmonary history , and baseline pulmonary function . Pulmonary function studies were performed preoperatively and on postoperative days 1 , 2 , 3 , and 7 . Oxygen saturation and chest radiographs were performed on both groups preoperatively and on postoperative day 1 . Postoperative pain was evaluated using a visual analog scale and the amount of narcotic consumed was recorded . Data are presented as mean + /- st and ard deviation . RESULTS Laparoscopic GBP patients had significantly less impairment of pulmonary function than open GBP patients on the first three postoperative days ( p < 0.05 ) . By the 7th postoperative day , all pulmonary function parameters in the laparoscopic GBP group had returned to within preoperative levels , but only one parameter ( peak expiratory flow ) had returned to preoperative levels in the open GBP group . On the first postoperative day , laparoscopic GBP patients used less morphine than open GBP patients ( 46 + /- 31 mg versus 76 + /- 39 mg , respectively , p < 0.001 ) , and visual analog scale pain scores at rest and during mobilization were lower after laparoscopic GBP than after open GBP ( p < 0.05 ) . Fewer patients after laparoscopic GBP than after open GBP developed hypoxemia ( 31 % versus 76 % , p < 0.001 ) and segmental atelectasis ( 6 % versus 55 % , p = 0.003 ) . CONCLUSION Laparoscopic gastric bypass result ed in less postoperative suppression of pulmonary function , decreased pain , improved oxygenation , and less atelectasis than open gastric bypass BACKGROUND To perform a prospect i ve , r and omized comparison of laparoscopic adjustable gastric b and ing ( LAGB ) and laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . METHODS LAGB , using the pars flaccida technique , and st and ard LRYGB were performed . From January 2000 to November 2000 , 51 patients ( mean age 34.0 + /- 8.9 years , range 20 - 49 ) were r and omly allocated to undergo either LAGB ( n = 27 , 5 men and 22 women , mean age 33.3 years , mean weight 120 kg , mean body mass index [ BMI ] 43.4 kg/m(2 ) ; percentage of excess weight loss 83.8 % ) or LRYGB ( n = 24 , 4 men and 20 women , mean age 34.7 , mean weight 120 kg , mean BMI 43.8 kg/m(2 ) , percentage of excess weight loss 83.3 ) . Data on the operative time , complications , reoperations with hospital stay , weight , BMI , percentage of excess weight loss , and co-morbidities were collected yearly . Failure was considered a BMI of > 35 at 5 years postoperatively . The data were analyzed using Student 's t test and Fisher 's exact test , with P < .05 considered significant . RESULTS The mean operative time was 60 + /- 20 minutes for the LAGB group and 220 + /- 100 minutes for the LRYGB group ( P < .001 ) . One patient in the LAGB group was lost to follow-up . No patient died . Conversion to laparotomy was performed in 1 ( 4.2 % ) of 24 LRYGB patients because of a posterior leak of the gastrojejunal anastomosis . Reoperations were required in 4 ( 15.2 % ) of 26 LAGB patients , 2 because of gastric pouch dilation and 2 because of unsatisfactory weight loss . One of these patients required conversion to biliopancreatic diversion ; the remaining 3 patients were on the waiting list for LRYGB . Reoperations were required in 3 ( 12.5 % ) of the 24 LRYGB patients , and each was because of a potentially lethal complication . No LAGB patient required reoperation because of an early complication . Of the 27 LAGB patients , 3 had hypertension and 1 had sleep apnea . Of the 24 LRYGB patients , 2 had hyperlipemia , 1 had hypertension , and 1 had type 2 diabetes . Five years after surgery , the diabetes , sleep apnea , and hyperlipemia had resolved . At the 5-year ( range 60 - 66 months ) follow-up visit , the LRYGB patients had significantly lower weight and BMI and a greater percentage of excess weight loss than did the LAGB patients . Weight loss failure ( BMI > 35 kg/m(2 ) at 5 yr ) was observed in 9 ( 34.6 % ) of 26 LAGB patients and in 1 ( 4.2 % ) of 24 LRYGB patients ( P < .001 ) . Of the 26 patients in the LAGB group and 24 in the LRYGB group , 3 ( 11.5 % ) and 15 ( 62.5 % ) had a BMI of < 30 kg/m(2 ) , respectively ( P < .001 ) . CONCLUSION The results of our study have shown that LRYGB results in better weight loss and a reduced number of failures compared with LAGB , despite the significantly longer operative time and life-threatening complications BACKGROUND Gastric bypass and duodenal switch are currently performed bariatric surgical procedures . Uncontrolled studies suggest that duodenal switch induces greater weight loss than gastric bypass . OBJECTIVE To determine whether duodenal switch leads to greater weight loss and more favorable improvements in cardiovascular risk factors and quality of life than gastric bypass . DESIGN R and omized , parallel-group trial . ( Clinical Trials.gov registration number : NCT00327912 ) SETTING 2 academic medical centers ( 1 in Norway and 1 in Sweden ) . PATIENTS 60 participants with a body mass index ( BMI ) between 50 and 60 kg/m(2 ) . INTERVENTION Gastric bypass ( n = 31 ) or duodenal switch ( n = 29 ) . MEASUREMENTS The primary outcome was the change in BMI after 2 years . Secondary outcomes included anthropometric measures ; concentrations of blood lipids , glucose , insulin , C-reactive protein , and vitamins ; and health-related quality of life and adverse events . RESULTS Fifty-eight of 60 participants ( 97 % ) completed the study . The mean reductions in BMI were 17.3 kg/m(2 ) ( 95 % CI , 15.7 to 19.0 kg/m(2 ) ) after gastric bypass and 24.8 kg/m(2 ) ( CI , 23.0 to 26.5 kg/m(2 ) ) after duodenal switch ( mean between-group difference , 7.44 kg/m(2 ) [ CI , 5.24 to 9.64 kg/m(2 ) ] ; P < 0.001 ) . Total cholesterol concentration decreased by 0.24 mmol/L ( CI , -0.03 to 0.50 mmol/L ) ( 9.27 mg/dL [ CI , -1.16 to 19.3 mg/dL ] ) after gastric bypass and 1.07 mmol/L ( CI , 0.79 to 1.35 mmol/L ) ( 41.3 mg/dL [ CI , 30.5 to 52.1 mg/dL ] ) after duodenal switch ( mean between-group difference , 0.83 mmol/L [ CI , 0.48 to 1.18 mmol/L ] ; 32.0 mg/dL [ CI , 18.5 to 45.6 mg/dL ] ; P ≤ 0.001 ) . Reductions in low-density lipoprotein cholesterol concentration , anthropometric measures , fat mass , and fat-free mass were also greater after duodenal switch ( P ≤ 0.010 for each between-group comparison ) . Both groups had reductions in blood pressure and mean concentrations of glucose , insulin , and C-reactive protein , with no between-group differences . The duodenal switch group , but not the gastric bypass group , had reductions in concentrations of vitamin A and 25-hydroxyvitamin D. Most Short Form-36 Health Survey dimensional scores improved in both groups , with greater improvement in 1 of 8 domains ( bodily pain ) after gastric bypass . From surgery until 2 years , 10 participants ( 32 % ) had adverse events after gastric bypass and 18 ( 62 % ) after duodenal switch ( P = 0.021 ) . Adverse events related to malnutrition occurred only after duodenal switch . LIMITATION Clinical experience was greater with gastric bypass than with duodenal switch at the study centers . CONCLUSION Duodenal switch surgery was associated with greater weight loss , greater reductions of total and low-density lipoprotein cholesterol concentrations , and more adverse events . Improvements in other cardiovascular risk factors and quality of life were similar after both procedures . PRIMARY FUNDING SOURCE South-Eastern Norway Regional Health Authority BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer BACKGROUND Hypercarbia and increased intraabdominal pressure during prolonged pneumoperitoneum can adversely affect cardiac function . This study compared the intraoperative hemodynamics of morbidly obese patients during laparoscopic and open gastric bypass ( GBP ) . METHODS Fifty-one patients with a body mass index ( BMI ) of 40 - 60 kg/m2 were r and omly allocated to undergo laparoscopic ( n = 25 ) or open ( n = 26 ) GBP . Cardiac output ( CO ) , mean pulmonary artery pressure ( MPAP ) , pulmonary artery wedge pressure ( PAWP ) , central venous pressure ( CVP ) , heart rate ( HR ) , and mean arterial pressure ( MAP ) were recorded at baseline , intraoperatively at 30-min intervals , and in the recovery room . Systemic vascular resistance ( SVR ) and stroke volume ( SV ) were also calculated . RESULTS The two groups were similar in terms of age , weight , and BMI . Operative time was longer in the laparoscopic than in the open group ( p < 0.05 ) . The HR and MAP increased significantly from baseline intraoperatively , but there was no significant difference between the two groups . In the laparoscopic group , CO was unchanged after insufflation , but it increased by 5.3 % at 2.5 h compared to baseline and by 43 % compared to baseline in the recovery room . In contrast , during open GBP , CO increased significantly by 25 % after surgical incision and remained elevated throughout the operation . CO was higher during open GBP than during laparoscopic GBP at 0.5 h and at 1 h after surgical incision ( p < 0.05 ) . During laparoscopic GBP , CVP , MPAP , and SVR increased transiently and PAWP remained unchanged . During open GBP , CVP , MPAP , and PAWP decreased transiently and SVR remained unchanged . There was no significant difference in the amount of intraoperative fluid administered during laparoscopic ( 5.5 + /- 1.6 L ) and open ( 5.6 + /- 1.7 L ) GBP . CONCLUSION Prolonged pneumoperitoneum during laparoscopic gastric bypass does not impair cardiac function and is well tolerated by morbidly obese patients Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P < 0.0001 ) and comparably after either procedure . Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P < 0.0001 ) and a significant suppression after the meal . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP Background The type of fundoplication that should be performed in conjunction with Heller myotomy for esophageal achalasia is controversial . We prospect ively compared anterior fundoplication ( Dor ) with partial posterior fundoplication ( Toupet ) in patients undergoing laparoscopic Heller myotomy . Methods A multicenter , prospect i ve , r and omized-controlled trial was initiated to compare Dor versus Toupet fundoplication after laparoscopic Heller myotomy . Outcome measures were symptomatic GERD scores ( 0–4 , five-point Likert scale question naire ) and 24-h pH testing at 6–12 months after surgery . Data are mean ± SD . Statistical analysis was by Mann – Whitney U test , Wilcoxon signed rank test , and Freidman ’s test . Results Sixty of 85 originally enrolled and r and omized patients who underwent 36 Dor and 24 Toupet fundoplications had follow-up data per protocol for analysis . Dor and Toupet groups were similar in age ( 46.8 vs. 51.7 years ) and gender ( 52.8 vs. 62.5 % male ) . pH studies at 6–12 months in 43 patients ( 72 % : Dor n = 24 and Toupet n = 19 ) showed total DeMeester scores and % time pH < 4 were not significant between the two groups . Abnormal acid reflux was present in 10 of 24 Dor group patients ( 41.7 % ) and in 4 of 19 Toupet patients ( 21.0 % ) ( p = 0.152 ) . Dysphagia and regurgitation symptom scores improved significantly in both groups compared to preoperative scores . No significant differences in any esophageal symptoms were noted between the two groups preoperatively or at follow-up . SF-36 quality -of-life measures changed significantly from pre- to postoperative for five of ten domains in the Dor group and seven of ten in the Toupet patients ( not significant between groups ) . Conclusion Laparoscopic Heller myotomy provides significant improvement in dysphagia and regurgitation symptoms in achalasia patients regardless of the type of partial fundoplication . Although a higher percentage of patients in the Dor group had abnormal 24-h pH test results compared to those of patients who underwent Toupet , the differences were not statistically significant BACKGROUND Controversy exists regarding the efficacy of heated and humidified intraperitoneal gases in maintaining core body temperature . We performed a sham-controlled study to test the hypothesis that active warming and humidification of the insufflation gas reduces intraoperative heat loss and improves recovery outcomes . PATIENTS AND METHODS Fifty morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass procedures using a st and ardized anesthetic technique were r and omly assigned to either a control ( sham ) group receiving room temperature insufflation gases with an inactive Insuflow ( Lexion Medical , St. Paul , MN ) device , or an active ( Insuflow ) group receiving warmed and humidified intraperitoneal gases . Esophageal and /or tympanic membrane temperature was measured perioperatively . Postoperative pain was assessed at 15 minute intervals using an 11-point verbal rating scale , with 0 = none to 10 = maximal . In addition , postoperative opioid requirements , incidence of nausea and vomiting , as well as the quality of recovery , were recorded . RESULTS Use of the active Insuflow device was associated with significantly higher mean + /- st and ard deviation ( SD ) intraoperative core body temperatures ( 35.5 + /- 0.5 vs. 35.0 + /- 0.4 degrees C ) . Postoperative shivering ( 0 vs. 19 % ) and the requirement for morphine in the postanesthesia care unit ( 5 + /- 4 vs. 10 + /- 5 mg ) were both significantly lower in the Insuflow vs. control groups . Patients in the Insuflow group also reported a higher quality of recovery 48 hours after surgery ( 15 vs. 13 , P < 0.05 ) . CONCLUSION The Insuflow device modestly reduced shivering and heat loss , as well as the need for opioid analgesics in the early postoperative period . However , it failed to improve laparoscopic visualization due to fogging , and provided improvement in the quality of recovery only on postoperative day 2 Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease ( GORD ) . Design Multicentre , pragmatic r and omised trial ( with parallel preference groups ) . Setting 21 hospitals in the United Kingdom . Participants 357 r and omised participants ( 178 surgical , 179 medical ) and 453 preference participants ( 261 , 192 ) ; mean age 46 ; 66 % men . All participants had documented evidence of GORD and symptoms for > 12 months . Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon . Those allocated to medical treatment had their treatment review ed and adjusted as necessary by a local gastroenterologist , and subsequent clinical management was at the discretion of the clinician responsible for care . Main outcome measures The disease specific REFLUX quality of life score ( primary outcome ) , SF-36 , EQ-5D , and medication use , measured at time points equivalent to three and 12 months after surgery , and surgical complications . Main results R and omised participants had received drugs for GORD for median of 32 months before trial entry . Baseline REFLUX scores were 63.6 ( SD 24.1 ) and 66.8 ( SD 24.5 ) in the surgical and medical r and omised groups , respectively . Of those r and omised to surgery , 111 ( 62 % ) actually had total or partial fundoplication . Surgical complications were uncommon with a conversion rate of 0.6 % and no mortality . By 12 months , 38 % ( 59/154 ) r and omised to surgery ( 14 % ( 14/104 ) among those who had fundoplication ) were taking reflux medication versus 90 % ( 147/164 ) r and omised medical management . The REFLUX score favoured the r and omised surgical group ( 14.0 , 95 % confidence interval 9.6 to 18.4 ; P<0.001 ) . Differences of a third to half of 1 SD in other health status measures also favoured the r and omised surgical group . Baseline scores in the preference for surgery group were the worst ; by 12 months these were better than in the preference for medical treatment group . Conclusion At least up to 12 months after surgery , laparoscopic fundoplication significantly increased measures of health status in patients with GORD . Trial registration IS RCT N15517081 Background : Hypercarbia and elevated intraabdominal pressure result ing from carbon dioxide ( CO2 ) pneumoperitoneum can adversely affect respiratory mechanics . This study examined the changes in mechanical ventilation , CO2 homeostasis , and pulmonary gas exchange in morbidly obese patients undergoing a laparoscopic or open gastric bypass ( GBP ) procedure . Methods : In this study , 58 patients with a body mass index ( BMI ) of 40 to 60 kg/m2 were r and omly allocated to laparoscopic ( n = 31 ) or open ( n = 27 ) GBP . Minute ventilation was adjusted to maintain a low normal arterial partial pressure of CO2 ( PaCO2 ) , low normal end-tidal partial pressure of CO2 ( ETCO2 ) , and low airway pressure . Respiratory compliance , ETCO2 , peak inspiratory pressure ( PIP ) , total exhaled CO2 per minute ( VCO2 ) , and pulse oximetry ( SO2 ) were measured at 30-min intervals . The acid – base balance was determined by arterial blood gas analysis at 1-h intervals . The pulmonary gas exchange was evaluated by calculation of the alveolar dead space – to – tidal volume ratio ( VDalv/VT ) and alveolar – arterial oxygen gradient ( PAO2–PaO2 ) . Results : The two groups were similar in age , gender , and BMI . As compared with open GBP , laparoscopic GBP result ed in higher ETCO2 , PIP , and VCO2 , and a lower respiratory compliance . Arterial blood gas analysis demonstrated higher PaCO2 and lower pH during laparoscopic GBP than during open GBP ( p < 0.05 ) . The VDalv/VT ratio and PAO2–PaO2 gradient did not change significantly during laparoscopic GBP . Intraoperative oxygen desaturation ( SO2 < 90 % ) did not develop in any of the patients in either group . Conclusions : Laparoscopic GBP alters intraoperative pulmonary mechanics and acid – base balance but does not significantly affect pulmonary oxygen exchange . Changes in pulmonary mechanics are well tolerated in morbidly obese patients when proper ventilator adjustments are maintained Background Laparoscopic sleeve gastrectomy ( LSG ) is a promising procedure for the surgical treatment of morbid obesity . We report our 2-year experience with LSG and specifically evaluate the importance of staple-line protection to prevent leakage after the laparoscopic procedure . Methods One hundred eighteen consecutive patients with BMI > 30 who underwent LSG from January 2006 to February 2009 were included in our study . There were 88 women and 30 men with a mean age of 33.2 ± 9.6 years and a mean BMI of 38.0 ± 6.4 kg/m2 . The first 40 patients ( group 1 ) underwent the operation without any reinforcement procedure and the other 78 patients received reinforcement of the staple-line ( group 2 ) . Data including demographics , hospital stay , blood loss , operative time , complications , excess weight loss percentage ( EWL% ) , and gastrointestinal quality of life index ( GIQLI ) were collected prospect ively for evaluation . Results The overall mean operative time was 118.5 ± 37.0 min , mean blood loss was 56.8 ± 56.7 ml , mean hospital stay was 5 ± 3 days . The mean EWL% at 12 and 24 months was 81.5 and 76.0 % , respectively . The overall leakage rate was 3.39 % ( 4/118 ) . All leakage occurred in group 1 patients , with a leakage rate of 10 % ( 4/40 ) . Mean preoperative GIQLI was 98.7 , and the postoperative GIQLI were 116.4 , 115 , 112.4 , and 97.6 at 3 , 6 , 12 , and 24 months , respectively . Conclusions LSG is an effective obesity treatment to achieve significant weight loss after 24 months . Staple-line reinforcement is strongly recommended for laparoscopic sleeve gastrectomy to decrease complications UNLABELLED We studied developments in indication , operation time , conversion rate , morbidity , and mortality from the beginning of laparoscopic cholecystectomy . Between 1990 and 2002 we prospect ively evaluated 4498 patients undergoing cholecystectomy ( CE ) , of whom 79 % were treated laparoscopically ( lap ) . In 6.6 % , the procedure had to be converted from laparoscopic to open cholecystectomy ( con ) , and 14 % were performed open from the beginning ( open ) . During the above time period , the rate of open CE decreased steadily ( 49 % in 1990 to 7.2 % in 2002 ) . The average operation time of lap CE remained constant with an average of 74 min ( range 20 - 330 ) . The conversion rate decreased in spite of broader indication for lap CE in even more complicated gallstone diseases , from an initial 9.4 % to 2.5 % . Among intraoperative complications in lap and con , bile duct lesions remained constant with 5/3856 ( 0.1 % ) , bleeding which led to conversion decreased from 1.9 % to 0.3 % , and the rate of gall bladder perforation increased from 12 % to 20.5 % . Thirty-day morbidity was 2 % in lap CE , 5 % in con , and 11.5 % in open . The mortality was 0 % in lap , 0.7 % in con , and 1 % in open . CONCLUSION Since the introduction of laparoscopic cholecystectomy the indication for this minimal-invasive operation steadily increased , the conversion-rate decreased and the complication-rate could be held low . Even with fast laparoscopic experience 7 % of all cholecystectomies are technically difficult and remain to be carried out primarily in an open technique . The laparoscopic cholecystectomy has become the gold st and ard in the therapy of gallstone disease Objective and Background : We lack long-term data ( > 10 years ) on the efficacy of antireflux surgery when evaluated within the framework of r and omized clinical trials Hereby we report the outcome of a r and omized trial comparing open total ( I ) and a Toupet posterior partial fundoplication ( II ) performed between 1983 and 1991 . Methods : One hundred and thirty-seven patients with gastroesophageal reflux disease and were enrolled into the study . The mean follow up has now reached 18 years . During these years 26 % had died and 16 % were unable to trace for follow up . Symptom outcomes were assessed by the use of vali date d self-reporting question naires . Results : Long-term control of heartburn and acid regurgitation ( reported as no or mild symptoms ) were reported by 80 % and 82 % after a total fundoplication ( I ) and corresponding figures were 87 % and 90 % after a partial posterior fundoplication ( II ) , respectively ( n.s . ) . The dysphagia scores were low 4.6 ± 1.3 ( SEM ) in group I and 3.3 ± 0.9 ( SEM ) in group II ( n.s ) . The point prevalences of rectal flatulence and gas distension related complaints were of similar magnitude in the 2 groups . Twenty-three percentage of the patients in the total fundoplication group noted some ability to vomit compared with 31 % in the partial posterior fundoplication group . Conclusions : Both a total and a partial posterior fundoplication maintain a high level of reflux control after 2 decades of follow up . The previously reported differences in mechanical side effects , in favor of the partial wrap , seemed to disappear over time . IS RCT N59614486 http://www.controlled-trials.com/IS RCT BACKGROUND Pneumoperitoneum has been shown to reduce hepatic portal blood flow and alter postoperative hepatic transaminases . This study evaluated the changes in hepatic function after laparoscopic and open gastric bypass ( GBP ) . METHODS Thirty-six morbidly obese patients were r and omly assigned to undergo either laparoscopic ( n = 18 ) or open ( n = 18 ) GBP . Liver function tests -- total bilirubin ( T Bil ) , gamma GT ( GGT ) , albumin , alkaline phosphatase ( ALP ) , aspartate transferase ( AST ) , alanine transferase (ALT)-- and creatine kinase levels were obtained preoperatively and at 1 , 24 , 48 , and 72 hours postoperatively . RESULTS The two groups were similar in age , sex , and body mass index . Albumin and ALP levels decreased while T Bil and GGT levels remained unchanged from baseline in both groups without significant difference between the two groups . After laparoscopic GBP , ALT and AST transiently increased by sixfold and returned to near baseline levels at 72 hours . After open GBP , ALT and AST transiently increased by fivefold to eightfold and returned to near baseline levels by 72 hours . Creatine kinase level was significantly lower after laparoscopic GBP than after open GBP at 48 and 72 hours postoperatively . There was no postoperative liver failure or mortality in either group . CONCLUSIONS Laparoscopic GBP result ed in transient postoperative elevation of hepatic transaminase ( ALT , AST ) but did not adversely alter hepatic function to any greater extent than open GBP . Creatine kinase levels were lower after laparoscopic GBP reflecting its lesser degree of abdominal wall trauma Objective : The aim of this study was to compare single-incision laparoscopic colectomy ( SILC ) to multiport laparoscopic colectomy ( MLC ) when performed by experienced laparoscopic surgeons . Background : Recent case reports and single institution series have demonstrated the feasibility of SILC . Few comparative studies for MLC and SILC have been reported . Methods : Patients from 5 institutions undergoing SILC were entered into an IRB approved data base from November 2008 to March 2010 . SILC patients were matched with those undergoing MLC for gender , age , disease , surgery , BMI , and surgeon . The primary endpoint was length of stay and secondary endpoints included operative time , conversion , complications and postoperative pain scores . Results : Three hundred thirty patients ( SILC = 165 , MLC = 165 ) were evaluated . Operative time ( 135 ± 45 min vs. 133 ± 56 min ; P = 0.85 ) and length of stay ( 4.6 ± 1.6 vs. 4.3 ± 1.4 ; P = 0.35 ) were not significantly different . Maximum postoperative day one pain scores were significantly less for SILC ( 4.9 vs. 5.6 ; P = 0.005 ) . Eighteen ( 11 % ) patients undergoing SILC were converted to multiport laparoscopy . There was no statistical difference between groups for conversions to laparotomy , complications , re-operations , or re-admissions . Conclusions : SILC is feasible when performed on select patients by surgeons with extensive laparoscopic experience . Outcomes were similar to MLC , except for a reduction in peak pain score on the first postoperative day . Prospect i ve r and omized trials should be performed before incorporation of this technology into routine surgical care Background : Gastric bypass and adjustable gastric b and ing are the 2 most commonly performed bariatric procedures for the treatment of morbid obesity . The aim of this study was to compare the outcomes , quality of life , and costs of laparoscopic gastric bypass versus laparoscopic gastric b and ing . Study Design : Between 2002 and 2007 , 250 patients with a body mass index of 35 to 60 kg/m2 were r and omly assigned to gastric bypass or gastric b and ing . After exclusion , 111 patients underwent gastric bypass and 86 patients underwent gastric b and ing . Outcome measures included demographic data , operative time , blood loss , length of hospital stay , morbidity , mortality , early and late reoperation rate , weight loss , changes in quality of life , and cost . Treatment failure was defined as losing less than 20 % of excess weight or conversion to another bariatric operation for failure of weight loss . Results : There were no deaths at 90 days in either group . The mean body mass index was higher in the gastric bypass group ( 47.5 vs. 45.5 kg/m2 , respectively , P < 0.01 ) while the mean age was higher in the gastric b and group ( 45 vs. 41 years , respectively , P < 0.01 ) . Compared with gastric b and ing , operative blood loss was higher and the mean operative time and length of stay were longer in the gastric bypass group . The 30-day complication rate was higher after gastric bypass ( 21.6 % vs. 7.0 % for gastric b and ) ; however , there were no life-threatening complications such as leaks or sepsis . The most frequent late complication in the gastric bypass group was stricture ( 14.3 % ) . The 1-year mortality was 0.9 % for the gastric bypass group and 0 % for the gastric b and group . The percent of excess weight loss at 4 years was higher in the gastric bypass group ( 68 ± 19 % vs. 45 ± 28 % , respectively , P < 0.05 ) . Treatment failure occurred in 16.7 % of the patients who underwent gastric b and ing and in 0 % of those who underwent gastric bypass , with male gender being a predictive factor for poor weight loss after gastric b and ing . At 1-year postsurgery , quality of life improved in both groups to that of US norms . The total cost was higher for gastric bypass as compared with gastric b and ing procedure ( $ 12,310 vs. $ 10,766 , respectively , P < 0.01 ) . Conclusions : Laparoscopic gastric bypass and gastric b and ing are both safe and effective approaches for the treatment of morbid obesity . Gastric bypass result ed in better weight loss at medium- and long-term follow-up but was associated with more perioperative and late complications and a higher 30-day readmission rate . There was a wide variation in weight loss after gastric b and ing with a small proportion of patients considered as treatment failure , and male gender was a predictive factor for poor weight loss Objective : To analyze long-term weight loss , changes in comorbidities and quality of life , and late complications after laparoscopic and open gastric bypass . Summary Background Data : Early results from our prospect i ve r and omized trial comparing the outcome of laparoscopic versus open gastric bypass demonstrated less postoperative pain , shorter length of hospital stay , fewer wound-related complications , and faster convalescence for patients who underwent laparoscopic gastric bypass . Methods : Between May 1999 and March 2001 , 155 morbidly obese patients were enrolled in this prospect i ve trial , in which 79 patients were r and omized to laparoscopic gastric bypass and 76 to open gastric bypass . Two patients in the laparoscopic group required conversion to open surgery ; their data were analyzed within the laparoscopic group on an intention-to-treat basis . The 2 groups were well matched for body mass index , age , and gender . Outcome evaluation included weight loss , changes in comorbidities and quality of life , and late complications . Results : The mean follow-up was 39 ± 8 months . There were no significant differences in the percent of excess body weight loss between the 2 groups at the 3-year follow-up ( 77 % for laparoscopic versus 67 % for open ) . The rate of improvement or resolution of comorbidities was similar between groups . Improvement in quality of life , measured by the Moorehead-Ardelt Quality of Life Question naire , was observed in both groups without significant differences between groups . Late complications were similar between groups except for the rate of incisional hernia , which was significantly greater after open gastric bypass ( 39 % versus 5 % , P < 0.01 ) , and the rate of cholecystectomy , which was greater after laparoscopic gastric bypass ( 28 % versus 5 % , P = 0.03 ) . Conclusions : In this r and omized trial with a 3-year follow-up , we found that laparoscopic gastric bypass was equally effective as open gastric bypass with respect to weight loss and improvement in comorbidities and quality of life . A major advantage at long-term follow-up for patients who underwent laparoscopic gastric bypass was the reduction in the rate of incisional hernia BACKGROUND Intraoperative oliguria is common during laparoscopic operations . The objective of this study was to evaluate the effects of prolonged pneumoperitoneum during laparoscopic gastric bypass ( GBP ) on intraoperative urine output and renal function . METHODS 104 patients with a body mass index between 40 and 60 kg/m2 were r and omly assigned to laparoscopic ( n = 54 ) or open ( n = 50 ) GBP . Intraoperative urine output was recorded at 30-min intervals . Blood urea nitrogen and creatinine levels were measured at baseline and on postoperative days 1 , 2 , and 3 . Levels of antidiuretic hormone , aldosterone , and plasma renin activity were also measured in a subset of laparoscopic ( n = 22 ) and open ( n = 24 ) GBP patients at baseline , 2 hours after surgical incision , and in the recovery room . RESULTS The laparoscopic and open groups were similar in age , gender , and body mass index . There was no significant difference in amount of intraoperative fluid administered between groups ( 5.4 + /- 1.6 L , laparoscopic versus 5.8 + /- 1.7 L , open ) , but operative time was longer in the laparoscopic group ( 232 min versus 200 min , p < 0.01 ) . Urinary output during laparoscopic GBP was 64 % lower than during open GBP at 1 hour after surgical incision ( 19 mL versus 55 mL , p < 0.01 ) and continued to remain lower than that of the open group by 31 - 50 % throughout the operation . Postoperative blood urea nitrogen and creatinine levels remained within the normal range in both groups . Serum levels of antidiuretic hormone , aldosterone , and plasma renin activity peaked at 2 hours after surgical incision with no significant difference between the two groups . CONCLUSION Prolonged pneumoperitoneum during laparoscopic gastric bypass significantly reduced intraoperative urine output but did not adversely alter postoperative renal function Objective : The purpose of this study was to evaluate the quality of life ( QOL ) after laparoscopy-assisted distal gastrectomy ( LADG ) compared with open distal gastrectomy ( ODG ) in patients with early gastric cancer . Summary Background Data : LADG has been beneficial in terms of pain , recovery , and morbidity when compared with open surgery with equal oncologic outcome . There has been no clinical study on QOL . Methods : From July 2003 to November 2005 , 164 patients with newly diagnosed cT1N0M0 and cT1N1M0 distal gastric cancer were r and omly assigned either to LADG or ODG . All patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 question naires preoperatively and postoperatively on regular follow-up visits . Results : Statistically significant differences were observed with a more favorable outcome noted in the LADG group with respect to intraoperative blood loss ( P < 0.001 ) , total amount of analgesics used ( P = 0.019 ) , the size of the wound ( P < 0.0001 ) , postoperative hospital stay ( P < 0.0001 ) , and QOL parameters of global health ( P < 0.0001 ) . Most of the scales on patient functioning including physical ( P < 0.0005 ) , role ( P = 0.0011 ) , emotional ( P < 0.0001 ) , social ( P < 0.0001 ) , and symptom scales such as fatigue ( P < 0.0001 ) , pain ( P < 0.0001 ) , appetite loss ( P = 0.031 ) , sleep disturbance ( P = 0.003 ) , dysphasia ( P = 0.0024 ) , gastro-esophageal reflux ( P = 0.0127 ) , dietary restriction ( P = 0.0004 ) , anxiety ( P = 0.0036 ) , dry mouth ( P = 0.0007 ) , and body image ( P < 0.0001 ) were also significantly better in the LADG group compared with the ODG group . Conclusions : Comparison of LADG to ODG in patients with early gastric cancer result ed in improved QOL outcomes in the patients followed for up to 3 months in the LADG group Background : Increased intra-abdominal pressure ( IAP ) postoperatively can adversely affect cardiovascular , pulmonary , and renal function . In this prospect i ve , r and omized trial , we compared the IAP in morbidly obese patients after laparoscopic and open gastric bypass ( GBP ) surgery . Methods : 64 patients with a body mass index of 40 to 60 kg/m2 were r and omized to undergo laparoscopic or open GBP.IAPs were obtained at baseline ( after induction of anesthesia ) , immediately after the operation , and on post-operative day ( POD ) 1 , 2 , and 3 . Intraoperative and postoperative fluid requirements , urine output , and creatinine clearance were recorded . Results : Demographics of the two groups were similar . IAP increased from baseline immediately after laparoscopic and open GBP ( p < 0.05 ) . IAP returned to baseline by POD 2 after laparoscopic GBP but remained elevated through POD 3 after open GBP . In fact , IAP was lower after laparoscopic GBP than after open GBP on POD 1 , 2 and 3 ( p < 0.05).The amount of intraoperative IV fluid was similar between groups , but laparoscopic GBP required less IV fluid and facilitated higher urine output post-operatively than open GBP.There was no significant difference in creatinine clearance between groups . Conclusions : Laparoscopic GBP result ed in significantly lower IAP , less postoperative fluid required , and greater postoperative urine output than open GBP Objective : The aim of this study was to evaluate the safety of this trial with respect to morbidity and mortality . Summary Background Data : Laparoscopic-assisted distal gastrectomy ( LADG ) is rapidly gaining popularity . However , there is limited evidence regarding its oncologic safety . We therefore conducted a phase III multicenter , prospect i ve , r and omized study comparing LADG with open gastrectomy ( ODG ) . Methods : Patient eligibility criteria were pathologically-proven adenocarcinoma , 20 to 80 years of age , preoperative stage I , no history of other cancer , chemotherapy , or radiotherapy . The primary end point was to determine whether there is a difference in overall survival between 2 groups . The morbidity and mortality were compared to evaluate the safety of this trial . The time was decided on the hypothesis that the morbidity of this trial was not significantly different from that of previous reports on open gastric cancer surgeries ( 17%–20 % ) . This study is registered at Clinical Trials.gov and carries the following ID number : NCT00452751 . Results : A total of 342 patients were r and omized ( LADG , 179 patients ; ODG , 161 patients ) between January 1 , 2006 and July 19 , 2007 . There were no significant differences between the 2 groups in age , gender , and comorbidities . The postoperative complication rates of the LADG and ODG groups were 10.5 % ( 17/179 ) and 14.7 % ( 24/163 ) , respectively ( P = 0.137 ) . Reoperations were required in 3 cases each group . The postoperative mortality was 1.1 % ( 2/179 ) and 0 % ( 0/163 ) in the LADG and ODG groups ( P = 0.497 ) , respectively . Conclusion : There was no significance difference in the morbidity and mortality between the 2 groups . Therefore , we conclude that this trial is safe and is thus ongoing Transumbilical single‐incision laparoscopic cholecystectomy ( SILC ) and minilaparoscopic cholecystectomy ( MLC ) are both increasingly being used to treat symptomatic gallstones . The present study compared SILC and MLC with respect to outcome in a prospect i ve r and omized trial Background : Pneumoperitoneum ( PP ) and the reverse Trendelenburg ( RT ) position have been shown to decrease femoral blood flow , result ing in venous stasis . However the effects of PP and RT on femoral venous flow have not been evaluated in morbidly obese patients undergoing laparoscopic gastric bypass ( GBP ) . We analyzed the effects of PP and RT on peak systolic velocity and the cross-sectional area of the femoral vein during laparoscopic and open GBP . We further examined the efficacy of intermittent sequential compression devices in reversing the reduction of femoral peak systolic velocity . Methods : Thirty patients with a body mass index ( BMI ) of 40–60 were r and omly allocated to under go either laparoscopic ( n = 14 ) or open ( n = 16 ) GBP . A duplex ultrasound examination of the femoral vein was performed at baseline , during PP and combined PP and RT in the laparoscopic group , and at baseline and during RT in the open group . The ultrasound exam was performed first without the use of sequential compression devices and then with the sequential compression devices inflated to 45 mmHg . Results : The two groups were similar in age , sex , BMI , and calf and thigh circumferences . During laparoscopic GBP , PP result ed in a 43 % decrease in peak systolic velocity and a 52 % increase in the cross-sectional area of the femoral vein ; the combination of PP and RT decreased peak systolic velocity to 57 % of baseline and increased the femoral cross-sectional area to 121 % of baseline . During laparoscopic GBP , the use of sequential compression devices during PP and RT partially reversed the reduction of femoral peak systolic velocity , but femoral peak systolic velocity was still lower than baseline by 38 % . During open GBP , RT result ed in a 38 % reduction in peak systolic velocity and a 69 % increase in the cross-sectional area of the femoral vein ; the use of sequential compression devices during RT partially reversed these changes by increasing femoral peak systolic velocity by 26 % ; however , it was still lower than baseline by 22 % . Conclusions : Pneumoperitoneum and reverse Trendelenburg position during laparoscopic and open GBP are independent factors for the development of venous stasis . Combining the reverse Trendelenburg position with pneumoperitoneum during laparoscopic GBP further reduces femoral peak systolic velocity and hence increases venous stasis . The use of sequential compression devices was partially effective in reversing the reduction of femoral peak systolic velocity , but it did not return femoral peak systolic velocity to baseline levels Objective : We hypothesized that laparoscopic cholecystectomy performed within 48 hours of admission for mild gallstone pancreatitis , regardless of resolution of abdominal pain or abnormal laboratory values , would result in a shorter hospital stay . Summary of Background Data : Although there is consensus among surgeons that patients with gallstone pancreatitis should undergo cholecystectomy to prevent recurrence , the precise timing of laparoscopic cholecystectomy for mild disease remains controversial . Methods : Consecutive patients with mild pancreatitis ( Ranson score ≤3 ) were prospect ively r and omized to either an early laparoscopic cholecystectomy group ( within 48 hours of admission ) versus a control laparoscopic cholecystectomy group ( performed after resolution of abdominal pain and normalizing trend of laboratory enzymes ) . The primary end point was hospital length of stay . Secondary end point was a composite of rates of conversion to an open procedure , perioperative complications , and need for endoscopic retro grade cholangiography . The study was design ed to enroll 100 patients with an interim analysis after 50 patients . Results : At interim analysis , 50 patients were enrolled at a single university-affiliated public hospital . Of them , 25 patients were r and omized to the early group and 25 patients to the control group . Patient age ranged from 18 to 74 years with a median duration of symptoms of 2 days upon presentation and a median Ranson score of 1 . There were no baseline differences between the groups with regards to demographics , clinical presentation , or the presence of comorbidities . The hospital length of stay was shorter for the early cholecystectomy group ( mean : 3.5 [ 95 % CI , 2.7–4.3 ] , median : 3 [ IQR , 2–4 ] ) compared with the control group ( mean : 5.8 [ 95 % CI , 3.8–7.9 ] , median : 4 [ IQR , 4–6 ] [ P = 0.0016 ] ) . Six patients from the early group required endoscopic retro grade cholangiography , compared with 4 in the control group ( P = 0.72 ) . There was no statistically significant difference in the need for conversion to an open procedure or in perioperative complication rates between the 2 groups . Conclusion : In mild gallstone pancreatitis , laparoscopic cholecystectomy performed within 48 hours of admission , regardless of the resolution of abdominal pain or laboratory abnormalities , results in a shorter hospital length of stay with no apparent impact on the technical difficulty of the procedure or perioperative complication rate Background : Laparoscopic appendectomy through a single umbilical incision is an emerging approach supported by several case series . However , to date , prospect i ve comparative data are lacking . Therefore , we conducted a prospect i ve , r and omized trial comparing single site umbilical laparoscopic appendectomy to 3-port laparoscopic appendectomy . Methods : After Internal Review Board approval , patients were r and omized to laparoscopic appendectomy via a single umbilical incision or st and ard 3-port access . The primary outcome variable was postoperative wound infection . Using a power of 0.9 and an alpha of 0.05 , 180 patients were calculated for each arm . Patients with perforated appendicitis were excluded . The technique of ligation/division of the appendix and mesoappendix was left to the surgeon 's discretion . There were 7 participating surgeons dictated by the call schedule . All patients received the same preoperative antibiotics and postoperative management was controlled . Results : There were 360 patients were enrolled between August 2009 and November 2010 . There were no differences in patient characteristics at presentation . There was no difference in wound infection rate , time to regular diet , length of hospitalization , or time to return to full activity . Operative time , doses of narcotics , surgical difficultly and hospital charges were greater with the single site approach . Also , the mean operative time was 5 minutes longer for the single site group . Conclusion : The single site umbilical laparoscopic approach to appendectomy produces longer operative times result ing in greater charges . However , these small differences are likely of marginal clinical relevance . The study was registered with clinical trials.gov at the inception of enrollment ( NCT00981136 ) BACKGROUND Laparoscopic surgery for colon cancer has been proven safe , but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer . The aim of the COlon cancer Laparoscopic or Open Resection ( COLOR ) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer . METHODS Between March 7 , 1997 , and March 6 , 2003 , patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2 ) were r and omly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority r and omised trial . Disease-free survival at 3 years after surgery was the primary outcome , with a prespecified non-inferiority boundary at 7 % difference between groups . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , and blood loss during surgery . Neither patients nor health-care providers were blinded to patient groupings . Analysis was by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT00387842 . FINDINGS During the recruitment period , 1248 patients were r and omly assigned to either open surgery ( n=621 ) or laparoscopic surgery ( n=627 ) . 172 were excluded after r and omisation , mainly because of the presence of distant metastases or benign disease , leaving 1076 patients eligible for analysis ( 542 assigned open surgery and 534 assigned laparoscopic surgery ) . Median follow-up was 53 months ( range 0.03 - 60 ) . Positive resection margins , number of lymph nodes removed , and morbidity and mortality were similar in both groups . The combined 3-year disease-free survival for all stages was 74.2 % ( 95 % CI 70.4 - 78.0 ) in the laparoscopic group and 76.2 % ( 72.6 - 79.8 ) in the open-surgery group ( p=0.70 by log-rank test ) ; the difference in disease-free survival after 3 years was 2.0 % ( 95 % CI -3.2 to 7.2 ) . The hazard ratio ( HR ) for disease-free survival ( open vs laparoscopic surgery ) was 0.92 ( 95 % CI 0.74 - 1.15 ) . The combined 3-year overall survival for all stages was 81.8 % ( 78.4 - 85.1 ) in the laparoscopic group and 84.2 % ( 81.1 - 87.3 ) in the open-surgery group ( p=0.45 by log-rank test ) ; the difference in overall survival after 3 years was 2.4 % ( 95 % CI -2.1 to 7.0 ; HR 0.95 [ 0.74 - 1.22 ] ) . INTERPRETATION Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95 % CI for the difference just exceeded the predetermined non-inferiority boundary of 7 % . However , the difference in disease-free survival between groups was small and , we believe , clinical ly acceptable , justifying the implementation of laparoscopic surgery into daily practice . Further studies should address whether laparoscopic surgery is superior to open surgery in this setting Background : Intraoperative hypothermia is a common event during open and laparoscopic abdominal surgery . The aim of this study was to compare changes in core temperature between laparoscopic and open gastric bypass ( GBP ) . Methods : 101 patients with a body mass index ( BMI ) of 40 - 60 kg/m2 were r and omly assigned to open ( n=50 ) or laparoscopic ( n=51 ) GBP . Anesthetic technique was similar for both groups . An external warming blanket and passive airway humidification were used intraoperatively . Core temperature was recorded at preanesthesia , at baseline ( after induction ) and at 30-min intervals ; intra-abdominal temperature was additionally measured at 30-min intervals in a subset of 30 laparoscopic GBP patients .The number of patients who developed intraoperative and postoperative hypothermia ( < 36 ° C ) was recorded . Length of operation for both groups and the amount of CO2 gas delivered during laparoscopic operations were also recorded . Results : There was no significant difference between groups with respect to age , gender , mean BMI , and amount of intravenous fluid administered . After induction of anesthesia , core temperature significantly decreased in both groups ; 36 % of patients in the open group and 37 % of patients in the laparoscopic group developed hypothermia . This percentage increased to 46 % in the open group and 41 % in the laparoscopic group during the operation , and then decreased to 6 % in the open group and 8 % in the laparoscopic group in the recovery-room . Core temperature increased during the operative procedure to reach 36.5 ± 0.6 ° Cin the open group and 36.3 ± 0.5 ° Cin the laparoscopic group at 2.5 hours after surgical incision . Intra-abdominal temperature during laparoscopic GBP was significantly lower than core temperature at all measurement points ( p<0.05 ) . Operative time was longer in the laparoscopic group than in the open group ( 232 ± 43 vs 201 ± 38 min , p<0.01 ) . Mean volume of gas delivered during laparoscopic GBP was 650 ± 220 liters . Conclusion : Perioperative hypothermia was a common event during both laparoscopic and open GBP . Despite a longer operative time , laparoscopic GBP did not increase the rate of intraoperative hypothermia when efforts were made to minimize intraoperative heat loss Laparoscopic Roux‐en‐$\font\ss = cmss10 scaled 1000 \hbox{Y}$ gastric bypass ( LRYGB ) and laparoscopic biliopancreatic diversion with duodenal switch ( LDS ) are surgical options for superobesity . A r and omized trial was conducted to evaluate perioperative ( 30‐day ) safety and 1‐year results BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
11,236 | 28,958,796 | MAIN RESULTS The tape has undergone substantial changes over the years , but there was no evidence to show that the changes have improved weight-estimation performance .
The overestimation of weight in low- and middle-income countries was often extreme .
This indicated a significant potential for potentially harmful medication errors .
The limited available evidence on the value of the tape as a drug-dosing guide indicated that the tape was frequently used incorrectly and contained insufficient information to function without additional re sources .
The Broselow tape lacked sufficient accuracy as a weight estimation and drug-dosing tool when compared to other available techniques .
In addition , the Broselow tape contains insufficient drug-dosing information to function as a complete resuscitation aid without additional material . | AIMS The Broselow tape is widely used as a weight-estimation device and drug-dosing guide aid , but concerns about its accuracy and its efficacy have emerged in the last decade .
The aim of this study was to systematic ally review the literature to analyse the accuracy of the Broselow tape as a weight estimation device and review evidence of its utility as a drug-dosing guide . | BACKGROUND Accurate children 's weight estimation is necessary and important for emergency pediatric care , particularly for drug dosages , electrical therapy , or equipment sizes . Children 's weight is difficult to measure in critically ill patients . Several methods were developed to estimate children 's accurate weight . Most methods were developed from western countries . The methods used currently might not work with Thai children . OBJECTIVE To determine the accuracy of the Broselow tape , family member estimation and the 50th percentile of national weight for height correlation graph for Thai children 's weight estimation . MATERIAL AND METHOD The authors carried out a prospect i ve study . Children from neonate to 12 years old who presented to the emergency department and general outpatient pediatric clinic were included . The patients were studied in both overall and subgroup analysis ( less than 10 kg , 10 to 25 kg , 25 to 40 kg , and over 40 kg ) . The primary outcome was the accuracy within 10 % error of the measured weight and the mean difference of the weight . RESULTS Five hundred ninety five patients were included in the present study . There were 333 ( 55.97 % ) boys and 262 ( 44.03 % ) girls . Family member estimation was the most accurate method with the accuracy within 10 % error 85.21 % and had the lowest mean difference ( -0.262 kg ) . Family members could estimate weight accurately for all weight subgroups . The Broselow tape was the second most accurate method with the accuracy within 10 % error 56.13 % and the low mean difference ( -0.485 kg ) . The accuracy within 10 % error of the 50th percentile of national weight for height correlation graph was 51.43 % and the mean difference was -0.648 kg . Every method had the best estimation in the weight subgroup 10 to 25 kg except the Broselow tape . CONCLUSION Family member estimation was the most accurate method in the present study . The family member could estimate the children 's weight within 10 % error of the measured weight about 85 % of cases . In case where family member estimation was not available , the Broselow tape was the next accurate alternative method Background The Broselow tape ( BT ) has been shown to estimate weight poorly primarily because of variations in body habitus . The manufacturers have suggested that a visual assessment of habitus may be used to increase its performance . This study evaluated the ability of habitus-modified models to improve the accuracy thereof . Methods A post hoc analysis of prospect ively collected data from four hospitals in Johannesburg , South Africa , on a population of 1,085 children . Sixteen a priori models generated a modified weight estimation or drug dose based on the BT weight and a gestalt assessment of habitus . Results The habitus-modified method suggested by the manufacturer did not improve the accuracy of the BT . Five dosing and four weight-estimation models were identified that markedly improved dosing and weight estimation accuracy , respectively . The best dosing model improved dosing accuracy ( doses within 10 % of correct dose ) from 52.0 to 69.6 % and reduced critical dosing errors from 16.5 to 4.3 % . The best weight-estimation model improved accuracy from 59.4 to 81.9 % and reduced critical errors from 11.8 to 1.9 % . Conclusion The accuracy of the BT as a drug-dosing and weight-estimation device can be substantially improved by including an appraisal of body habitus in the methodology Objective Obtaining an accurate weight is crucial during pediatric trauma/medical resuscitation . Currently , length-based weight estimations are used . Study objective was to assess feasibility of obtaining actual weights of children during trauma resuscitation and study its concordance with length-based estimated weight using the Broselow Pediatric Emergency Tape . Methods Pediatric trauma patients 0 to 14 years old presenting to a tertiary care pediatric trauma center between November 2008 and October 2009 were enrolled prospect ively . Length-based weight estimation was done on patient arrival using the Broselow tape ; in addition , an actual patient weight was recorded using the trauma stretcher integrated weighing scale . Results Two hundred thirty-one patients were eligible and enrolled . Weights were recorded in 145 children ( 63.2 % ) . In 27 patients ( 18.6 % ) whose body length exceeded Broselow tape range , weight was measured using stretcher scale only . The remaining 118 patients ( mean age , 5.0 [ SE ± 0.3 ] years ; 67 % male ) were used for correlation analysis . There was good correlation ( Pearson correlation coefficient , r = 0.86 ) between estimated weight and measured weight . However , Bl and -Altman analysis showed mean bias + 2.6 kg ( 95 % confidence interval [ CI ] , 1.6–3.6 kg ) ; lower/upper limits of agreement were −8.3 kg ( CI , −10.0 to −6.6 kg ) and 13.5 kg ( CI , 11.7–15.2 kg ) . Conclusions It is possible to obtain an actual patient weight during pediatric trauma resuscitation . Length-based estimated weight using Broselow tape underestimated weight by 2.6 kg ; the mean error was greatest in the highest weight category Background In paediatric resuscitation , for a rapid and accurate estimate of children 's weight , the Broselow tape can be used in children who are 46–144 cm tall . The Broselow tape has previously been found to provide the most accurate estimate of children 's weight internationally , but it is not known how many fall outside the range of the tape , or whether such children can be assumed to be of adult weight , or how otherwise to estimate the weight of these children . Objectives To determine what proportion of children in different age groups falls outside the limits of the Broselow tape , how their weight compares with that of the adults and what correlates most strongly with weight in these children . Methods This was a population -based prospect i ve observational study of Chinese children up to 12 years old , from schools in Hong Kong . Weight was measured to the nearest 0.2 kg , and the height , foot-length and mid-arm circumference ( MAC ) were measured to the nearest 0.1 cm . Results 40 % of 10-year olds and 70 % of 11-year olds were too tall for the tape . Their median weight was 41.9 kg . This was significantly less than the median weight of 18-year olds ( 55 kg , p<0.0001 ) in Hong Kong . The strongest correlate with weight in these children was MAC . Conclusions The Broselow tape is inappropriate for use in most children over 10 years old . Children too tall for the tape can not be assumed to be of adult weight ; to do so would imply an average overestimate of 30 % . Weight estimates in older children could be based on MAC OBJECTIVES . The purpose of this study was to compare the predictive accuracy of 3 methods ( Broselow tape , Leffler formula , and Theron formula ) for pediatric weight estimation to identify factors that can influence weight estimation , and to derive alternative models for such estimation if indicated . METHODS . This was a prospect i ve , nonblinded observational study . Every patient in the cohort was ≤10 years of age . The patients ’ age and height were used to estimate their weight by using the 3 previously mentioned methods . These estimated weights were compared with the patients ’ actual weight by using the modified Bl and -Altman method . RESULTS . One thous and eleven subjects were included . Percent differences between predicted and actual weight were significantly less using the Broselow tape compared with other methods for patients weighing < 10 or 10 to 25 kg and for the Theron formula compared with other methods for patients weighing > 40 kg . For patients weighing 25.1 to 40 kg , performance of the Broselow tape and Leffler method were similar , and both were superior to the Theron formula . Three weight predictors ( age , gender , and ethnicity ) were identified , and 2 new weight-estimation models were derived from the cohort . CONCLUSIONS . The Broselow tape is accurate for weight estimation in children ≤25 kg , but the Theron formula performs better with patients weighing > 40 kg . The Broselow tape was not statistically superior to the Leffler formula in subjects weighing 25.1 to 40 kg . A separate cohort is needed to evaluate the validity of the alternative predictive formulae Objective . Significant attention has been paid to weight estimation in setting s where scales are impractical or unavailable ; however , no studies have evaluated the performance of published weight estimation methods in children with Down syndrome . This study was design ed to evaluate the predictive performance of various methods in this population with well-established differences in height and weight for age . Methods . This was a prospect i ve study of children aged 0 to 18 years with Down syndrome . Anthropometric measurements including height , weight , humeral length , and mid-upper arm circumference were collected and applied to 4 distinct weight estimation strategies based on age ( APLS ) , length ( Broselow ) , habitus ( Cattermole ) , and length plus habitus ( Mercy ) . Predictive performance was evaluated by examining residual error ( RE ) , percentage error ( PE ) , root mean square error ( RMSE ) , limits of agreement , and intraclass correlation coefficients . Results . A total of 318 children distributed across age , gender , and body mass index percentile were enrolled . APLS and Mercy showed the smallest degree of bias ( PE = 7.8 ± 24.5 % and −3.9 ± 12.4 % , respectively ) . Broselow suffered the most extreme underestimation ( −63 % ) , whereas the APLS suffered the greatest degree of overestimation ( 107 % ) . Mercy demonstrated the highest intraclass correlation coefficient ( 0.987 vs 0.867 - 0.885 ) and predicted weight within 20 % of actual in the largest proportion of participants ( 88 % vs 40 % to 76 % ) . All methods were less robust in children with Down syndrome than reported for unaffected children . Conclusions . Mercy offered the best option for weight estimation in children with Down syndrome . Additional anthropometric data collected in this special population would allow investigators to refine existing weight estimation strategies specifically for these children Objectives The aims of the study were to examine the predictive accuracy of Broselow tape ( BT ) weight estimation and body mass index – based weight categorization in overweight and obese pediatric patients and to develop an adjustment factor that improves the BT weight estimate in overweight and obese pediatric patients . Methods A prospect i ve observational study was conducted . We enrolled noncritical pediatric patients presenting to a tertiary care pediatric emergency department with nonurgent complaints . Patients had their weights , heights , abdominal circumferences , and actual BT measurements documented by research staff . Results One hundred seventy-eight patients aged 2 to 18 years were enrolled . Using the Centers for Disease Control and Prevention 's definition of body mass index classification , 71 patients ( 39.89 % ) had normal BMI , 43 patients ( 24.16 % ) were overweight , and 64 patients ( 35.96 % ) were obese . The accuracy of the BT-estimated weight range , compared with the actual weight , is 40.5 % in our study population . When stratified by BMI classification , the accuracy proportions were the following : 71.8 % for normal , 41.9 % for overweight , and 4.7 % for obese patients . The adjustment formula ( [ 0.014 × waistline in cm + 0.3 ] × BT weight ) improved overall weight estimation from 40.5 % to 65.2 % . The greatest improvement was noted in obese children , where the BT accuracy improved from 4.7 % to 59.4 % . Conclusions The growing pediatric obesity epidemic has challenged the BT 's ability to accurately estimate the weights in overweight and obese pediatric patients . Our study demonstrated inverse relationship between the accuracy of BT and body weight . An adjustment factor significantly improved BT accuracy in obese children OBJECTIVE The Broselow Pediatric Emergency Tape ( Armstrong Medical Industries , Inc. , Lincolnshire , IL ) ( BT ) is a well-established length-based tool for estimation of body weight for children during resuscitation . In view of p and emic childhood obesity , the BT may no longer accurately estimate weight . We therefore studied the BT in children from Ontario in a large recent patient cohort . METHODS Actual height and weight were obtained from an urban and a rural setting . Children were prospect ively recruited between April 2007 and July 2008 from the emergency department and outpatient clinics at the London Health Science Centre . Rural children from junior kindergarten to grade 4 were also recruited in the spring of 2008 from the Avon Maitl and District School Board . Data for preschool children were obtained from three daycare centres and the electronic medical record from the Maitl and Valley Medical Centre . The predicted weight from the BT was compared to the actual weight using Spearman rank correlation ; agreement and percent error ( PE ) were also calculated . RESULTS A total of 6,361 children ( 46.2 % female ) were included in the study . The median age was 3.9 years ( interquartile range [ IQR ] 1.56 - 7.67 years ) , weight was 17.2 kg ( IQR 11.6 - 25.4 kg ) , and height was 103.5 cm ( IQR 82 - 124.4 cm ) . Although the BT weight estimate correlated with the actual weight ( r = 0.95577 , p < 0.0001 ) , the BT underestimated the actual weight by 1.62 kg ( 7.1 % ± 16.9 % SD , 95 % CI -26.0 - 40.2 ) . The BT had an ≥ 10 % PE 43.7 % of the time . CONCLUSIONS Although the BT remains an effective method for estimating pediatric weight , it was not accurate and tended to underestimate the weight of Ontario children . Until more accurate measurement tools for emergency departments are developed , physicians should be aware of this discrepancy Background This study aims to remodel the Broselow Pediatric Emergency Tape for the Indian pediatric population . The Broselow tape overestimates the heights of the Indian pediatric population and remits inaccurate predicted weights for all color zones with varying degrees and could result in overresuscitation of Indian children in emergency setting s. The Indian children are underweight for their age and height . Methods We prospect ively collected cross-sectional data on a sample of 1185 children aged 1 month to 12 years old in Chennai , India . The Broselow tape was used for length-based weight estimation , and actual weight was recorded by a weighing scale . In the first stage , we recruited 769 children . With univariate linear regression , we adjusted the Broselow tape by an 8 % correction factor to enhance accuracy and created a new tape with new weight and height ranges . In the second stage , we recruited 416 children and tested the new ranges for accuracy . Results The Broselow tape overestimates weights with a mean percentage difference of 5–15 % depending on the color zone . Accuracy of the Broselow tape by color-coded zone was between 33–86.6 % , with higher weight color zones showing lower accuracy . The new Indian pediatric weight estimation tool ( IPWET ) , based on the Broselow tape has a weight range of 4–36 kg and height range of 50–150 cm ( Broselow tape , 3–36 kg , 46–146.5 cm ) and an improved accuracy between 51–97.8 % . Conclusions A remodeled Broselow tape can predict weights with higher accuracy in the Indian pediatric population BACKGROUND The Broselow tape is one method for rapid weight estimation in pediatric patients undergoing resuscitation , but it does not perform equally in all population s. To date , we are unaware of any study evaluating its use in a Latin American population . OBJECTIVE To investigate the accuracy of the Broselow tape in a Mexican emergency department ( ED ) . METHODS We conducted a prospect i ve , observational study of children presenting to a Mexican ED . Patient weight was estimated using the Broselow tape and the estimate compared to their weight measured on a scale . Research ers were blinded to scale weight and Broselow categories . For analysis , the Broselow tape 's nine color zones were divided into three weight categories . RESULTS Of 815 subjects , 356 ( 43.7 % ) were female . In children weighing < 10 kg , the tape tended to underestimate weight , whereas it overestimated weight in the other two weight categories . The mean percentage difference between the actual weight and the Broselow tape-predicted weight was <3 % in each category , although it differed significantly across the three weight categories . Accuracy of the predicted weight to within 10 % of actual weight was lowest for children weighing < 10 kg , at 46.2 % ( confidence interval [ CI ] ± 6.4 % ) , and greatest for those in the 10 - 18-kg weight category , at 64.1 % ( CI ± 5.1 % ) . However , the correlation of color zones predicted by both methods was highest for subjects < 10 kg at 64.4 % ( CI ± 6.1 % ) . It was significantly lower in the other weight categories at 54.5 % ( CI ± 5.3 ) for subjects weighing 10 - 18 kg , and 50.1 % ( CI ± 6.4 % ) for subjects weighing > 18 kg . The percentage of children for whom the color code differed by two or more categories was < 4 % overall and for each weight category . CONCLUSION The Broselow tape-estimated weight was different from the scale weight by more than 10 % in a substantial percentage of Mexican children . Nevertheless , the mean percentage difference was < 3 % , and Broselow tape color zone estimation was accurate in the majority of subjects , suggesting its use would result in clinical ly appropriate dosing and equipment estimations . Further research is needed to vali date its use in this clinical setting Background We sought to vali date the accuracy and assess the efficacy of a newly developed electronic weight estimation device ( ie , the rolling tape ) for paediatric weight estimation . Methods We enrolled a convenience sample of children aged < 17 years presenting to our emergency department who volunteered to participate in the study . The children 's heights and weights were measured , and three research ers estimated these values using the rolling tape and Broselow tape at 5 min intervals . The weight estimates of research er 1 , research er 2 and the Broselow tape were compared with measured values , and mean percentage error ( MPE ) , root mean square error ( RMSE ) and percentage of estimates within 10 % of the actual measured values were calculated . For 30 r and omly selected subjects , we compared the time interval from the start of the measurement to the time that orders for epinephrine , defibrillation dose and instrument size could be given in a simulated arrest scenario . Results We enrolled 906 children ( median age 4.0 years ) . For research er 1 , research er 2 and the Broselow tape , MPE values were 0.11 % ( RMSE 2.61 kg ) , 1.41 % ( RMSE , 2.61 kg ) and 1.72 % ( RMSE 5.41 kg ) , respectively , and the percentages of children with predictions within 10 % of their actual weight were 75.1 % , 75.7 % and 60.6 % , respectively . In the 30 simulated cases , the mean time for measurement to ordering was significantly shorter ( 25.8 s vs 35.5 s , p<0.001 ) for the rolling tape compared with the Broselow tape method . Conclusions The rolling tape is a good weight estimation tool for children compared with other methods . The rolling tape method significantly decreased the time from weight estimation to orders for essential drug dose , instrument size and defibrillation dose for resuscitation Background . Access to resuscitation equipment is a critical component in delivering optimal care in pediatric arrest situations . Historically , children 's hospitals and clinics have used a st and ard pediatric resuscitation cart ( “ st and ard cart ” ) in which drawers are organized by intervention ( eg , intubation module , intravenous module ) , requiring multiple drawers to be opened during a code . Many emergency departments , however , use a pediatric resuscitation cart based on the Broselow tape ( “ Broselow cart ” ) in which each drawer is color coded and organized by patient length and weight ranges ; each drawer contains all necessary equipment for resuscitation of a patient in that specific length/weight range . A literature review has revealed no studies examining the utility of either cart . Objectives . To compare which resuscitation cart organization ( st and ard versus Broselow ) allows for faster access to equipment , more accurate selection of appropriately sized equipment , and better user satisfaction . Methodology . We performed a prospect i ve , r and omized , controlled , crossover trial in which 21 pediatric health care providers were assigned the role of obtaining the appropriate equipment during 2 st and ardized , simulated codes alternately using either a st and ard or Broselow cart . Time to and accuracy of the selection of appropriate medical equipment along with posttesting satisfaction were measured . All simulations were performed in the Center for Advanced Pediatric Education at Stanford University Medical Center ( Stanford , CA ) , a training facility design ed to replicate the real medical environment with the technology to allow for videotaping of scenarios . Results . Of the 21 subjects , 62 % found the Broselow cart “ easy ” or “ very easy ” to use versus 33 % for the st and ard cart . Of the 21 subjects , 67 % preferred the Broselow cart , 10 % preferred the st and ard cart , and 23 % indicated no preference . Intubation supplies and nasogastric tubes were found significantly faster when using the Broselow cart ( mean time : 29.1 and 20 seconds , respectively ) versus the st and ard cart ( mean time : 38.7 and 38.2 seconds , respectively ) . Correct equipment was provided a statistically significant 99 % of the time with the Broselow cart versus 83 % of the time with the st and ard cart . Ten percent of the subjects had prior experience with the Broselow cart versus 62 % having experience with the st and ard cart . Conclusions . Despite less prior experience with the Broselow cart , subjects in this study found it easier to use and preferred it over the st and ard cart . In addition , subjects located intubation equipment and nasogastric tubes significantly faster when using the Broselow cart , and correct equipment was provided significantly more often with the Broselow cart . These data suggest that sites caring for pediatric patients should consider modeling their resuscitation carts after the Broselow cart to enhance provider confidence and patient safety Objective To prospect ively compare the actual weights of Australian children in an ethnically diverse metropolitan setting with the predicted weights using the Paediatric Advanced Weight Prediction in the Emergency Room ( PAWPER ) tape , Broselow tape , Mercy system and calculated weights using the up date d Advanced Paediatric Life Support ( APLS ) , Luscombe and Owens and Best Guess formulae . Methods A prospect i ve , cross-sectional , observational , blinded , convenience study conducted at the Children 's Hospital at Westmead Paediatric Emergency Department in Sydney , Australia . Comparisons were made using Bl and -Altman plots , mean difference , limits of agreement and estimated weight within 10 % and 20 % of actual weight . Results 199 patients were enrolled in the study with a mean actual weight of 27.2 kg ( SD 17.2 ) . Length-based tools , with or without body habitus adjustment , performed better than age-based formulae . When measuring estimated weight within 10 % of actual weight , PAWPER performed best with 73 % , followed by Mercy ( 69 % ) , PAWPER with no adjustment ( 62 % ) , Broselow ( 60 % ) , Best Guess ( 47 % ) , Luscombe and Owens ( 41 % ) and revised APLS ( 40 % ) . Mean difference was similar across all methods ranging from 0.4 kg ( 0.0 , 0.9 ) for Mercy to −2.2 kg ( −3.5 , −0.9 ) for revised APLS . Limits of agreement were narrower for the length-based tools ( −5.9 , 6.8 Mercy ; −8.3 , 5.6 Broselow ; −9.0 , 7.1 PAWPER adjusted ; −12.1 , 9.2 PAWPER unadjusted ) than the age-based formulae ( −18.6 , 17.4 Best Guess ; −19.4 , 15.1 revised APLS , −21.8 , 17.7 Luscombe and Owens ) . Conclusion In an ethnically diverse population , length-based methods with or without body habitus modification are superior to age-based methods for predicting actual body weight . Body habitus modifications increase the accuracy and precision slightly OBJECTIVE Validation of the ' Best Guess ' weight estimation method on a geographically divergent external sample of children , plus comparison with APLS and Broselow weight estimation methods . METHODS Prospect i ve cross-sectional analytical study at Princess Margaret Hospital Emergency Department . A convenience sample of children aged 0 - 14 years recruited from May to June 2008 . Age , sex , ethnicity , height and actual weight obtained . Agreement between the methods is reported as a comparative mean and distribution of the percentage error , plus the proportion of instances where the error exceeded 20 % of the measured weight . RESULTS A total of 1235 children were included . The ' Best Guess ' method was the most accurate , particularly in children aged 1 - 4 years ( mean percentage error + 1.69 % ) . In other age groups it overestimated weight , with mean percentage errors ranging from 3.41 % to 6.25 % . Across all age groups the Broselow method was most precise , with tendency to underestimate weight across age groups with mean percentage errors ranging from -5.28 % to -7.24 % . The APLS method was least accurate and precise , with mean percentage errors ranging from -12.61 % to -17.36 % . Net weight underestimation errors exceeding 20 % were associated with increased mean body mass index . CONCLUSION The Best Guess weight estimation method is accurate , especially in children aged 1 - 4 years . It moderately overestimates weight in other ages . The Broselow method was more precise , whereas the APLS method was the least accurate and precise of all . The ease of use of the Broselow method argues for greater use in the ED and prehospital setting STUDY OBJECTIVE We compare time to drug delivery and the incidence of dosage error between 2 different systems of medication administration : The Broselow Pediatric Emergency Tape and a st and ardized volume/weight-based dose reformulation of resuscitation and critical care medications ( reformulated to 0.1 mL/kg ) . METHODS This was a r and omized crossover trial , in which volunteers ( n=16 ) from emergency department ( ED ) pediatric resuscitation teams from the ED of a large , urban , teaching hospital in Australia were assigned to manage simulated ( Advanced Pediatric Life Support scenario ) patients . The volunteers were each presented with 3 case scenarios ( brady-asystolic arrest , status epilepticus , and rapid sequence intubation requiring administration of 4 , 5 , and 4 medications , respectively ) . The order of presentation was r and omized for the 2 methods . The volunteers were then asked to manage 3 case scenarios using one and then the other method ( result ing in a total of 6 cases managed per participant ) . The dosage of each medication ordered , as well as the time to the simulated administration of that medication , was recorded for all scenarios . The expected dosages were compared with the actual dosages delivered to determine which system provided greater accuracy in medication administration . Statistical analysis was undertaken using the Wilcoxon signed rank test and McNemars test for paired proportions . RESULTS Compared with the Broselow tape , the st and ardized volume/weight-based dose reformulation significantly reduced median time to medication delivery for all clinical scenarios ( 147 versus 72 seconds ; 197 versus 87 seconds ; 146 versus 64 seconds ; P<.001 ) . The proportion of dosing errors with Broselow tape across the 3 scenarios was greater than with volume/weight-based dosing ( 0.08 versus 0 , 0 versus 0 , and 0.08 versus 0.02 , respectively ) . CONCLUSION Use of a st and ardized volume/weight-based dose reformulation method is a simple , fast , and accurate method of medication delivery for the pediatric patient that eliminates the need for memorization and /or calculation . The st and ardized volume/weight-based dose reformulation method performs better than the Broselow tape in speed of delivery of medications used for pediatric resuscitation and critical care without any reduction in dosing accuracy BACKGROUND AND OBJECTIVE Weight estimation for pediatric resuscitation occurs frequently in emergency departments . Historically , different approaches to estimation have been studied with varied results . With increasing obesity rates among inner-city children , this study aims to determine the best method for pediatric weight estimation in our population . METHODS This is a prospect i ve , nonblinded , observational study . A total of 324 patients ( aged 1 month to 12 years ) were enrolled in the study to exceed sample size calculations . The accuracy of 4 methods for weight estimation -- the Broselow tape , advanced pediatric life support formulas , the PAWPER tape , and mid-arm circumference formula -- were compared across age ranges and body sizes to determine the most appropriate method for our population . RESULTS In this inner-city population , 32 % of the patients 2 to 12 years of age were found to be overweight or obese . This rate increased to 41 % for patients 6 to 12 years of age . In this setting , the PAWPER tape outperformed the other 3 methods , estimating patients ' weight within ±5 % of actual weight in 35.2 % of our cohort . When compared with the other 3 methods tested , the PAWPER tape was statistically superior with a P value less than .02 in each case . CONCLUSION Each of the methods tested in our population performed poorly . Current methods for weight estimation should be used with caution , especially for population s with an increased prevalence of obesity . Efforts should be dedicated to improving or deriving new methods for weight estimation that perform better in this vulnerable population Context : The Broselow Pediatric Resuscitation Tape has been shown to be effective in reducing medication dosing error among pediatric emergency providers . However , the tape has often been used inappropriately or incorrectly . Objective : To evaluate whether a Web-based education program on proper use of the tape could reduce medication dosing errors and time to determine dose . Design , Setting , and Participants : A r and omized , controlled trial conducted among 89 pediatric emergency providers from 3 study sites . Intervention : All study subjects participated in a videotaped simulated stabilization scenario and were then r and omly assigned to control or education group . After the intervention , all subjects participated in another simulation . Main Outcomes Measures : The primary outcomes included dosing deviation from accepted dose range for each medication prescribed and dosing deviation summary , calculated by averaging dosing deviation for all medications . The secondary outcomes included time to determine a dose for each medication prescribed , and dosing time summary ; that is , the average time to determine doses for all medications prescribed . Results : No significant difference was observed in the demographic characteristics of the 2 groups . After the educational intervention , the average ( 12.6 % vs. 24.9 % ) and median ( 7.1 % vs. 20.1 % ) dosing deviation summary were much lower in the education group than in the control group . The difference in the median dosing deviation summary between the 2 groups was statistically significant ( P = 0.0002 ) . Similar results were observed for the dosing time . The education group demonstrated a lower average ( 16 vs. 20 seconds ) and lower median ( 15 vs. 18 seconds ) dosing time summary than the control group . The difference in the median dosing time summary between the 2 groups was statistically significant ( P = 0.02 ) . Analysis of each medication prescribed indicated that the decrease in the dosing deviation and dosing time in the education group was most obvious for several specific medications . Conclusions : The Web-based education program on the proper use of the Broselow Pediatric Resuscitation Tape could improve dosing accuracy and reduce dosing time Objective We compared performance characteristics of 7 weight estimation methods examining predictive performance and human factors errors . Methods This was a prospect i ve study of 80 emergency care providers ( raters ) and 80 children aged 2 months to 16 years . Raters estimated weights in 5 children with the following 7 strategies : visual estimation , Advanced Pediatric Life Support , Luscombe and Owens , Broselow tape , devised weight estimation method , 2D Mercy TAPE ( 2DT ) , and 3D Mercy TAPE ( 3DT ) . Quantitative errors were determined by checking rater values against values returned with optimal method use . Results Four hundred rater-child pairings generated 2800 weight estimates . For all methods , rater-estimated weights were less accurate than weights derived by optimal application . Skill-based , perception , and judgment/decision error were observed . For visual estimation , weights were underestimated in most children . For Advanced Pediatric Life Support/Luscombe and Owens , order of operations markedly impacted errors with 23 % of calculations requiring addition first performed incorrectly versus 9 % of calculations requiring multiplication first . For Broselow tape , only 63 % of cases were eligible for estimation with this device , yet raters assigned a weight in 96 % of cases . For Devised Weight Estimation Method , 96 % of overweight and 48 % of obese children were classified as slim or average . For 2DT/3DT , the 2DT was prone to more errors most commonly use of the wrong side of the device ( 24 % ) . The impact of rater characteristics on error was most pronounced for methods requiring calculation . Conclusions Skill-based , perception , or judgment errors were observed in more than 1 of 20 cases . No singular strategy was used with 100 % accuracy AIMS Weight estimations in children , which are required when actual weight can not be measured , are often very inaccurate because of variations in body habitus not accounted for in the estimating methodology . This study was conducted to evaluate the accuracy of the PAWPER tape , a new two-step weight-estimation tape device which employs a length-based habitus-modified weight estimation system . METHODS This was a prospect i ve study in the Emergency Departments of two hospitals in Johannesburg , South Africa on a population of children aged from 1 month to 12 years . Each child had their weight estimated by both the Broselow tape and the PAWPER tape . These weight estimates were then compared against measured weight to determine the bias and precision of the estimation techniques . RESULTS The PAWPER tape performed well , and better than the Broselow tape in every analysis performed . The mean percentage error was -3.8 % vs. 0 % and the root mean squared percentage error was 9.1 % vs. 4.5 % for the Broselow tape and PAWPER tape , respectively ( p<0.0001 ) . The Broselow tape predicted weight to within 10 % of actual weight in 63.6 % of children and the PAWPER tape in 89.2 % ( p<0.0001 ) . The difference between the performances of the Broselow tape and PAWPER tape was most pronounced in children > 20 kg , and in children above or below average weight-for-length . CONCLUSIONS The PAWPER tape has been shown to be a simple and reliable method of weight estimation in children and infants . The inclusion of an appraisal of body habitus in the methodology considerably improved the accuracy of weight estimation OBJECTIVES We sought to evaluate commonly used paediatric weight estimation techniques in a sample of children in the Philippines . METHODS We prospect ively collected age , height and weight data for a sample of 207 children aged 1 - 9 years seen during a medical aid trip . Weights were estimated using the finger counting method , the Broselow method and four formulae . Bl and -Altman analysis was performed to evaluate agreement with measured weight . RESULTS Mean difference and range of agreement in kilograms were as follows : 0.6 ( 95 % CI 0.1 - 1.1 ) and 14.9 ( 95 % CI 13.1 - 16.7 ) for the Broselow method ; 1.1 ( 95 % CI 0.5 - 1.7 ) and 17.3 ( 95 % CI 15.2 - 19.3 ) for the traditional APLS formula ; 3.1 ( 95 % CI 2.4 - 3.7 ) and 18.6 ( 95 % CI 16.4 - 20.8 ) for the finger counting method ; 4.0 ( 95 % CI 3.2 - 4.8 ) and 23.1 ( 95 % CI 20.3 - 25.8 ) for the up date d APLS method ; 5.1 ( 95 % CI 4.4 - 5.8 ) and 21.1 ( 95 % CI 18.6 - 23.6 ) for the Luscombe formula ; and 5.3 ( 95 % CI 4.5 - 6.1 ) and 22.5 ( 95 % CI 20 - 25.2 ) for the Best Guess formulae . CONCLUSIONS The Broselow tape and the traditional APLS formula performed best in our sample . The finger counting method also outperformed newer weight estimation formulae . ' Up date d ' age-based formulae created recently in developed countries should not be used in disaster relief efforts in the Philippines . Caution should be used when applying these formulae to other developing countries and in disaster response OBJECTIVE Methods to estimate weights of children requiring resuscitation appeared to underestimate the weight of Pacific Isl and and Maori children . This study sought to quantify differences between real and estimated weights , study links with ethnicity and derive a new estimation method for large-for-age children . METHOD Data were collected prospect ively for 3 months . Weights were estimated by formulae described by Shann , Leffler , the Advanced Paediatric Life Support ( APLS ) formula , the Oakley resuscitation chart and the Broselow tape . RESULTS Of the 909 children included , 46 % were of Pacific Isl and and 25 % were of Maori origin . Differences between actual and estimated weights were significantly greater ( P<0.05 ) for the Pacific Isl and group using all methods of estimation . Maori differences were significantly greater than European differences using Oakley and Broselow methods ( P<0.05 ) . The Broselow tape was the method most likely to underestimate weight in Pacific Isl and and Maori children . A new formula was derived from non-linear regression analysis , leading to a new chart . CONCLUSION Current emergency methods underestimate weight in Pacific Isl and and Maori children . We recommend a new chart for these children OBJECTIVE Medication errors are a common cause of iatrogenic morbidity and mortality . The incidence of medication errors in pediatric emergency departments ( EDs ) has not been described . The objective of this study was to describe the incidence and type of drug errors in a pediatric ED and determine factors associated with risk of errors . METHODS A retrospective cohort study was conducted of the charts of 1532 children who were treated in the ED of a pediatric tertiary care hospital during 12 r and omly selected days from the summer of 2000 . Two pediatricians , blinded to other study variables , independently decided whether a medication error occurred and ranked it according to a severity score . Disagreement was resolved by consensus . RESULTS Prescribing errors were identified in 10.1 % of the charts . The following variables were associated in univariate analysis with an increased proportion of errors : patients seen between 4 AM and 8 AM ( odds ratio [ OR ] : 2.45 ; 95 % confidence interval [ CI ] : 1.10 - 5.50 ) , patients with severe disease ( OR : 2.53 ; 95 % CI : 1.18 - 5.41 ) , medication ordered by a trainee ( OR : 1.48 ; 95 % CI : 1.03 - 2.11 ) , and patients seen during weekends ( OR : 1.48 ; 95 % CI : 1.04 - 2.11 ) . Among trainees , there was a higher rate of errors at the beginning of the academic year ( OR : 1.67 ; 95 % CI : 1.06 - 2.64 ) . Logistic regression revealed increased risk for errors when a medication was ordered by a trainee ( OR : 1.64 ; 95 % CI : 1.06 - 2.52 ) and in seriously ill patients ( OR : 1.55 ; 95 % CI : 1.06 - 2.26 ) . CONCLUSIONS In the pediatric ED , trainees are more likely to commit prescribing errors , and the most seriously ill patients are more likely to be subjected to prescribing errors Objectives : To evaluate differences in accuracy of 2 weight estimation methods for children when compared with measured weights : the Broselow-Luten tape ( patient 's height as the predictor ) and the devised weight estimation method ( DWEM ) ( patient 's height and body habitus as predictors ) . Methods : Information was obtained prospect ively on a convenience sample of patients presenting through triage on nonconsecutive days at the Children 's Hospital Emergency Department . Weight was measured in kilograms , and a measured length or height in centimeters was obtained , as well as 2 independent assessment s of body habitus . Weights were then estimated using the Broselow-Luten tape and the DWEM . This study evaluated 4 separate weight classes : less than or equal to 10 kg , 10.1 to 20 kg , 20.1 to 36 kg , and 36.1 kg or more . One hundred children were recruited into each weight class , for a total of 400 children . Comparisons of estimations with measured weights were made using the Pearson correlation coefficient method . Mean percentage errors were calculated for weight estimations by both methods . Results : Both the Broselow-Luten and DWEM weight estimations when compared with measured weights showed statistical correlation ( using the Pearson correlation coefficient ) . However , the Broselow-Luten method had a negative mean percentage error in all weight classes , and the DWEM had a negative mean percentage error in classes greater than 20 kg , indicating an underestimation of weight in those classes . Conclusions : Although both the Broselow-Luten and DWEM weight estimations show statistical correlation with measured weights , the Broselow-Luten method underestimates weights in all weight classes , and the DWEM underestimates weights in the weight classes greater than 20 kg Background : Prescribing medication appropriate to a child ’s bodily dimensions is fundamental to paediatric emergency medicine . Mathematical formulae are frequently used in clinical practice to estimate children ’s weights . In 1995 the UK ’s paediatric reference data , describing age-related changes in bodily proportions ( both weight and height ) , were up date d and published . This study assesses the validity of using mathematical estimates , age-based estimates or length-based estimates of weight ( the latter both compiled from this reference data ) by comparison with actual physical measurements recorded in a paediatric clinic setting . Methods : A prospect i ve study was carried out in a paediatric outpatient setting recording age , weight and height for statistical comparison with these three possible methods . Results : 544 children aged 0–11 years were recruited , with mean ( SD ) age , weight and height of 5.3 ( 2.9 ) years , 21.4 ( 10 ) kg and 108 ( 22 ) cm , respectively . Conclusions : Both length-based and age-based estimates of weight outperformed the currently accepted “ gold st and ard ” mathematical estimate when applied to children up to 11 years of age ( ∼35 kg ) . Length-based estimates were statistically superior , but the physical limitations and technical constraints posed when attempting to accurately measure a child ’s length in emergency environments may favour the simplicity of using the child ’s age against tables of growth chart reference data to provide an estimate of their weight STUDY OBJECTIVE We assessed the performance of 2 new devices ( 2D- and 3D-Mercy TAPE ) to implement the Mercy Method for pediatric weight estimation and contrasted their accuracy with the Broselow method . METHODS We enrolled children aged 2 months through 16 years in this prospect i ve , multicenter , observational study . Height/length , weight , humeral length , and mid-upper arm circumference were obtained for each child , using calibrated scales and measures . We then made measurements with blinded versions of the 2D- and 3D-TAPEs . Using height/length data , we calculated the weight estimated by the Broselow method . We contrasted measures with mean error , mean percentage error , and percentage predicted within 10 % and 20 % of actual . RESULTS Six hundred twenty-four participants ( median 8.5 years , 27.6 kg , 17.3 kg/m(2 ) ) completed the study . Mean error was 0.3 kg ( mean percentage error 1.6 % ) , 0.2 kg ( mean percentage error 1.9 % ) , and -1.3 kg ( mean percentage error -4.1 % ) for 2D- , 3D- , and Broselow , respectively . Concordance between both TAPE devices and the Mercy Method was greater than 0.99 . The proportion of children predicted within 10 % and 20 % of actual weight was 76 % and 98 % for the 2D-TAPE and 65 % and 93 % for the 3D-TAPE . Excluding the 209 ( 33 % ) children who were too tall for the device , Broselow predictions were within 10 % and 20 % of actual weight in 59 % and 91 % . CONCLUSION The 2D- and 3D-Mercy TAPEs outperform the Broselow tape for pediatric weight estimation and can be used in a wider range of children Rationale Accurate weight measurements are essential for both growth monitoring and drug dose calculations in children . Weight can be accurately measured using calibrated scales in re source -rich setting s ; however , reliable scales are often not available in re source -poor regions or emergency situations . Current age and /or length/height-based weight-prediction equations tend to overestimate weight because they were developed from Western children 's measures . Objective To determine the accuracy of several proxy measures for children 's weight among a predominately HIV-positive group of children aged 18 months to 12 years in Botswana . Design Weight , length/height , ulna and tibia lengths , mid-upper arm circumference ( MUAC ) and triceps skinfold were measured on 775 children recruited from Gaborone , Botswana , between 6 July and 24 August 2011 . Results Mean ( 95 % CI ) age and weight were 7.8 years ( 7.5 to 8.4 ) and 21.7 kg ( 21.2 to 22.2 ) , respectively . The majority of children were HIV-positive ( n=625 , 81 % ) and on antiretroviral treatment ( n=594 , 95 % ) . The sample was r and omly divided ; a general linear model was used to develop weight-prediction equations for one half of the sample ( n=387 ) , which were then used to predict the weight of the other half ( n=388 ) . MUAC and length/height , MUAC and tibia length and MUAC and ulna length most accurately predicted weight , with an adjusted R2 of 0.96 , 0.95 and 0.93 , respectively . Using MUAC and length/height , MUAC and tibia length and MUAC and ulna length equations , ≥92 % of predicted weight fell within 15 % of actual weight , compared with < 55 % using current equations . Conclusion The development of nomograms using these equations is warranted to allow for rapid and accurate weight prediction from these simple anthropometric measures in HIV-endemic , re source -constrained setting BACKGROUND The Broselow ™ Pediatric Emergency Tape indicates st and ardized , pre-calculated medication doses , dose delivery volumes , and equipment sizes using color-coded zones based on height-weight correlations . The present study attempted to provide more evidence on the effectiveness of the Broselow ™ Pediatric Emergency Tape by comparing the tape-estimated weights with actual weights . We hypothesized that the Broselow ™ Pediatric Emergency Tape would overestimate weights in Indian children aged<10 years , leading to inaccurate dosing and equipment sizing in the emergency setting . METHODS This prospect i ve study of pediatric patients aged < 10 years who were divided into three groups based on actual body weight : < 10 kg , 10 - 18 kg , and > 18 kg . We calculated the percentage difference between the Broselow-predicted weight and the measured weight as a measure of tape bias . Concordant results were those with a mean percent difference within 3 % . St and ard deviation was measured to determine precision . Accuracy was determined as color-coded zone prediction and measured weight concordance , including the percentage overestimation by 1 - 2 zones . RESULTS The male-to-female ratio of the patients was 1.3:1 . Total agreement between color-coding was 63.18 % ( κ=0.582 ) . The Broselow ™ color-coded zone agreement was 74.8 % in the < 10 kg group , 61.24 % in the 10 - 18 kg group , and 53.42 % in the > 18 kg group . CONCLUSIONS The Broselow ™ Pediatric Emergency Tape showed good evidence for being more reliable in children of the < 10 kg and 10 - 18 kg groups . However , as pediatric weight increased , predictive reliability decreased . This raises concerns over the use of the Broselow ™ Pediatric Emergency Tape in Indian children because body weight was overestimated in those weighing > 18 kg OBJECTIVES We compared the accuracy of a conceptually simple pediatric weight estimation technique , the finger counting method , with other commonly used methods . METHODS We prospect ively collected cross-sectional data on a convenience sample of 207 children aged 1 to 9 presenting to our pediatric emergency department . Bl and -Altman plots were constructed to compare the finger counting method to the Broselow tape method , parental estimate , the Luscombe formula , and the advanced pediatric life support ( APLS ) formula . Proportions within 10 % and 20 % of measured weight were compared . RESULTS Mean difference and range of agreement in kilograms for Bl and -Altman plots were as follows : -1.8 ( 95 % confidence interval [ CI ] , -2.3 to -1.3 ) and 15.4 ( 95 % CI , 13.6 - 17.2 ) for the finger counting method ; -1.4 ( 95 % CI , -2.0 to -0.9 ) and 15.8 ( 95 % CI , 13.9 - 17.6 ) for the Broselow method ; -0.02 ( 95 % CI , -0.53 to 0.49 ) and 14.8 ( 95 % CI , 13 - 16.6 ) for parental estimate ; 0.2 ( 95 % CI , -0.33 to 0.72 ) and 15.3 ( 95 % CI , 13.5 - 17.2 ) for the Luscombe formula ; and -3.8 ( 95 % CI , -4.4 to -3.2 ) and 17.2 ( 95 % CI , 15.2 - 19.2 ) for the APLS formula . The finger counting method estimated weights within 10 % in 59 % of children ( 95 % CI , 52%-65 % ) and within 20 % in 87 % of children ( 95 % CI , 81%-91 % ) . Proportions within 10 % were similar for all methods , except the APLS method , which was lower . CONCLUSIONS The finger counting method is an acceptable alternative to the Broselow method for weight estimation in children aged 1 to 9 years . It outperforms the traditional APLS method but underestimates weights compared with parental estimate and the Luscombe formula STUDY OBJECTIVE The Institute of Medicine has called on the US health care system to identify and reduce medical errors . Unfortunately , medication dosing errors remain commonplace and may result in potentially life-threatening outcomes , particularly for pediatric patients when dosing requires weight-based calculations . Novel medication delivery systems that may reduce dosing errors resonate with national health care priorities . Our goal was to evaluate novel , prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape , compared with conventional medication administration , in simulated pediatric emergency department ( ED ) resuscitation scenarios . METHODS We performed a prospect i ve , block-r and omized , crossover study in which 10 emergency physician and nurse teams managed 2 simulated pediatric arrest scenarios in situ , using either prefilled , color-coded syringes ( intervention ) or conventional drug administration methods ( control ) . The ED resuscitation room and the intravenous medication port were video recorded during the simulations . Data were extracted from video review by blinded , independent review ers . RESULTS Median time to delivery of all doses for the conventional and color-coded delivery groups was 47 seconds ( 95 % confidence interval [ CI ] 40 to 53 seconds ) and 19 seconds ( 95 % CI 18 to 20 seconds ) , respectively ( difference=27 seconds ; 95 % CI 21 to 33 seconds ) . With the conventional method , 118 doses were administered , with 20 critical dosing errors ( 17 % ) ; with the color-coded method , 123 doses were administered , with 0 critical dosing errors ( difference=17 % ; 95 % CI 4 % to 30 % ) . CONCLUSION A novel color-coded , prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by emergency physician and nurse teams during simulated pediatric ED resuscitations BACKGROUND Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes , particularly for pediatric patients where dosing often requires weight-based calculations . Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities . Our goal was to evaluate novel , prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape , compared to conventional medication administration , in simulated prehospital pediatric resuscitation scenarios . METHODS We performed a prospect i ve , block-r and omized , cross-over study , where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled , color-coded syringes ( intervention ) or their own medication kits stocked with conventional ampoules ( control ) . Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed . The ambulance patient compartment and the intravenous medication port were video recorded . Data were extracted from video review by blinded , independent review ers . RESULTS Median time to delivery of all doses for the intervention and control groups was 34 ( 95 % CI : 28 - 39 ) seconds and 42 ( 95 % CI : 36 - 51 ) seconds , respectively ( difference=9 [ 95 % CI : 4 - 14 ] seconds ) . Using the conventional method , 62 doses were administered with 24 ( 39 % ) critical dosing errors ; using the prefilled , color-coded syringe method , 59 doses were administered with 0 ( 0 % ) critical dosing errors ( difference=39 % , 95 % CI : 13 - 61 % ) . CONCLUSIONS A novel color-coded , prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations Abstract Background : The use of a length/weight-based tape ( LBT ) for equipment size and drug dosing for pediatric patients is recommended in a joint statement by multiple national organizations . A new system , known as H and tevy ™ , allows for rapid determination of critical drug doses without performing calculations . Objective : To compare two LBT systems for dosing errors and time to medication administration in simulated prehospital scenarios . Methods : This was a prospect i ve r and omized trial comparing the Broselow Pediatric Emergency Tape ™ ( Broselow ) and H and tevy LBT ™ ( H and tevy ) . Paramedics performed 2 pediatric simulations : cardiac arrest with epinephrine administration and hypoglycemia m and ating dextrose . Each scenario was repeated utilizing both systems with a 1-year-old and 5-year-old size manikin . Facilitators recorded identified errors and time points of critical actions including time to medication . Results : We enrolled 80 paramedics , performing 320 simulations . For Dextrose , there were significantly more errors with Broselow ( 63.8 % ) compared to H and tevy ( 13.8 % ) and time to administration was longer with the Broselow system ( 220 seconds vs. 173 seconds ) . For epinephrine , the LBTs were similar in overall error rate ( Broselow 21.3 % vs. H and tevy 16.3 % ) and time to administration ( 89 vs. 91 seconds ) . Cognitive errors were more frequent when using the Broselow compared to H and tevy , particularly with dextrose administration . The frequency of procedural errors was similar between the two LBT systems . Conclusion : In simulated prehospital scenarios , use of the H and tevy LBT system result ed in fewer errors for dextrose administration compared to the Broselow LBT , with similar time to administration and accuracy of epinephrine administration Abstract Background . The Broselow tape is widely used to rapidly estimate weight and facilitate proper medication dosing in pediatric patients . Objective . We aim ed to determine the accuracy of prehospital use of the Broselow tape . Methods . We prospect ively enrolled a consecutive sample of pediatric patients transported to the emergency department ( ED ) at Harbor – UCLA Medical Center from February 2008 to January 2009 . Eligible subjects arrived via ambulance and were less than 145 cm tall , the upper limit of height for Broselow measurements . Subjects were excluded if they had a medical condition preventing proper measurement ( e.g. , contractures ) . Per Los Angeles County protocol , paramedics obtained a Broselow weight on all pediatric patients . The paramedic Broselow weight was compared with the ED Broselow weight and the ED scale weight , which was obtained unless mobilization was contraindicated . Accuracy was determined by assessing Bl and -Altman plots and the Pearson correlation coefficient . As part of a sensitivity analysis , multiple imputation was used to account for missing data . Results . There were 572 subjects enrolled . The median age was 24 months ( interquartile range [ IQR ] 10 to 49 months ) ; 316 ( 55 % ) of the subjects were male . The weighted Cohen 's kappa assessing agreement between the paramedic and ED Broselow colors was 0.74 ( 95 % confidence interval [ CI ] 0.68 to 0.79 ) . The median difference between the paramedic Broselow weight and the scale weight was –0.10 kg ( IQR –1.7 to 0.7 ) . The accuracy of the paramedic Broselow weight when compared with the ED scale weight and the ED Broselow weight as defined by Pearson 's correlation coefficient was 0.92 ( 95 % CI 0.90 to 0.93 ) and 0.97 ( 95 % CI 0.97 to 0.98 ) , respectively . Multiple imputation for missing data did not alter the results . Conclusion . Paramedic Broselow weight correlates well with scale weight and ED Broselow weight . Paramedics can use the Broselow tape to accurately determine weight for pediatric patients in the prehospital setting BACKGROUND Pediatric medication dosing has been recognized as a high-error activity with the potential to cause serious harm . Few studies assess systems approaches to error reduction in pediatrics . OBJECTIVE To estimate the decrease in deviation from recommended medication doses associated with use of a pediatric intervention st and ardization system in the acute setting . DESIGN Two-period , 2-treatment crossover trial with data collected between December 1 , 1999 , and February 29 , 2000 . SETTING Tertiary , academic medical center . PARTICIPANTS Convenience sample of 28 resident physicians , representing 69 % of pediatrics and 50 % of medicine-pediatrics residents . INTERVENTION Each resident participated in 4 simulated pediatric resuscitations . The Broselow Pediatric Emergency Tape and color-coded material s were available in either the first or second 2 scenarios . Traditional dosing references were available in all scenarios . MAIN OUTCOME MEASURE Median difference between deviation from recommended dose range ( DRDR ) in scenarios where color coding was used ( intervention ) and DRDR in scenarios where color coding was not available ( control ) . RESULTS Median DRDR in intervention scenarios was 25.4 % lower than in control scenarios ( 95 % confidence interval [ CI ] , 19.1%-32.5 % ; P<.001 ) . In 4 medication prescriptions in intervention scenarios and in 54 prescriptions in control scenarios , DRDRs exceeded 100 % . Median deviation from recommended equipment sizes in intervention scenarios was 0.12 size lower than in control scenarios ( 95 % CI , 0.03 - 0.22 size ; P<.001 ) . Deviations in equipment size of 2 or more sizes were noted in 1 size determination in intervention scenarios and in 21 size determinations in control scenarios . CONCLUSIONS Color coding was associated with a significant reduction in deviation from recommended doses in simulated pediatric emergencies . Numerous potentially clinical ly significant deviations from recommended doses and equipment sizes were avoided . Future studies should measure impact in the real clinical setting OBJECTIVES The objective of this study was to develop and vali date a new age-based formula for estimating body weights of Korean children . METHODS We obtained body weight and age data from a survey conducted in 2005 by the Korean Pediatric Society that was performed to establish normative values for Korean children . Children aged 0 - 14 were enrolled , and they were divided into three groups according to age : infants ( < 12 months ) , preschool-aged ( 1 - 4 years ) and school-aged children ( 5 - 14 years ) . Seventy-five percent of all subjects were r and omly selected to make a derivation set . Regression analysis was performed in order to produce equations that predict the weight from the age for each group . The linear equations derived from this analysis were simplified to create a weight estimating formula for Korean children . This formula was then vali date d using the remaining 25 % of the study subjects with mean percentage error and absolute error . To determine whether a new formula accurately predicts actual weights of Korean children , we also compared this new formula to other weight estimation methods ( APLS , Shann formula , Leffler formula , Nelson formula and Broselow tape ) . RESULTS A total of 124,095 children 's data were enrolled , and 19,854 ( 16.0 % ) , 40,612 ( 32.7 % ) and 63,629 ( 51.3 % ) were classified as infants , preschool-aged and school-aged groups , respectively . Three equations , ( age in months+9)/2 , 2 × (age in years)+9 and 4 × (age in years)-1 were derived for infants , pre-school and school-aged groups , respectively . When these equations were applied to the validation set , the actual average weight of those children was 0.4 kg heavier than our estimated weight ( 95 % CI=0.37 - 0.43 , p<0.001 ) . The mean percentage error of our model ( + 0.9 % ) was lower than APLS ( -11.5 % ) , Shann formula ( -8.6 % ) , Leffler formula ( -1.7 % ) , Nelson formula ( -10.0 % ) , Best Guess formula ( + 5.0 % ) and Broselow tape ( -4.8 % ) for all age groups . CONCLUSION We developed and vali date d a simple formula to estimate body weight from the age of Korean children and found that this new formula was more accurate than other weight estimating methods . However , care should be taken when applying this formula to older children because of a large st and ard deviation of estimated weight INTRODUCTION Accurate measurement of children 's weight is rarely possible in paediatric resuscitation , and rapid estimates are made to ensure appropriate drug and fluid doses and equipment selection . Weight is commonly estimated from formulae based on children 's age , or from their height using the Broselow tape . Foot-length and mid-arm circumference have also been suggested as the basis of weight-estimation formulae . OBJECTIVES To determine which of age , height , foot-length or mid-arm circumference had the strongest relationship with weight in healthy children , to derive a simple weight-estimation formula from the strongest correlate , and to compare its performance with existing weight-estimation tools . METHODS This was a population -based prospect i ve observational study of Hong Kong Chinese children aged 1 - 11 years old last birthday . Weight was measured to the nearest 0.2 kg ; height , foot-length and mid-arm circumference to the nearest 0.1 cm . Multiple regression analysis was used to determine the strongest independent relationships with weight , and linear regression analysis derived a weight-estimation formula . Accuracy and precision of this formula were compared with st and ard age-based and height-based weight-estimation methods . RESULTS Mid-arm circumference had the strongest relationship with weight , and this relationship grew stronger with age . The formula , weight [kg]=(mid-arm circumference [cm]-10 ) x 3 , was at least as accurate and precise as the Broselow method and outperformed the age-based rule in school-age children , but was inadequate in pre-school children . CONCLUSION This weight-estimation formula based on mid-arm circumference is reliable for use in school-age children , and an arm-tape could be considered as an alternative to the Broselow tape in this population Objective To compare the time required to withdraw various pediatric resuscitation medications using traditional techniques and the Per-Kilo Doser ( PKD ) , a new weight-based dosing device . Methods Seven emergency department nurses were each videotaped as they withdrew medications for four different pediatric resuscitation scenarios . In r and om order , each nurse performed a total of eight timing trials — four with traditional techniques and four with the PKD . The videotapes were later review ed and timed by two review ers who were unaware of the study purpose . The time to drug withdrawal ( announcement of medication and dose to be withdrawn until the nurse completed medication withdrawal ) was measured in seconds . Nonparametric and exact techniques were used to determine statistical significance . Results Using traditional techniques , the mean time to drug withdrawal was 71.8 seconds ; using the PKD , the mean time to drug withdrawal was 43.1 seconds . The mean time difference between the PKD and traditional techniques was 29.2 seconds ( 95 % CI , 16.7–41.7 ) . Conclusion The PKD decreases medication withdrawal time Estimation methods for pediatric weight have not been evaluated for Japanese children . This study aim ed to assess the accuracy of mothers ' reports of their children 's weight in Japan . We also evaluated potential alternatives to the estimation of weight , including the Broselow tape ( BT ) , Advanced Pediatric Life Support ( APLS ) , and Park 's formulae . We prospect ively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers . Each weight estimation method was evaluated using Bl and - Altman plots and by calculating the proportion within 10 % and 20 % of the measured weight . Mothers ' reports of weight were the most accurate method , with 94.9 % within 10 % of the measured weight , the lowest mean difference ( 0.27 kg ) , and the shortest 95 % limit of agreement ( －1.4 to 1.9 kg ) . The BT was the most reliable alternative , followed by APLS and Park 's formulae . Mothers ' reports of their children 's weight are more accurate than other weight estimation methods . When no report of a child 's weight by the mother is available , BT is the best alternative . When an aged-based formula is the only option , the APLS formula is preferred STUDY OBJECTIVE Vali date d methods for weight estimation of children are readily available in developed countries ; however , their utility in developing countries with higher rates of malnutrition and infectious disease is unknown . The goal of this study is to determine the validity of a height-based estimate , the Broselow tape , compared with age-based estimations among pediatric patients in Western Kenya . METHODS A prospect i ve cross-sectional study of all sick children presenting to the emergency department of a government referral hospital in Eldoret , Kenya , was performed . Measured weight was compared with predicted weights according to the Broselow tape and commonly used advanced pediatric life support ( APLS ) and Nelson 's age-based formulas . A Bl and -Altman analysis was used to determine agreement between each method and actual weight . The method for weight prediction was determined a priori to be equivalent to the actual weight if the 95 % confidence interval for the mean percentage difference between the predicted and actual weight was less than 10 % . RESULTS Nine hundred sixty-seven children were included in analysis . The overall mean percentage difference for the actual weight and Broselow predicted weight was -2.2 % , whereas APLS and Nelson 's predictions were -5.2 % and -10.4 % , respectively . The overall agreement between Broselow color zone and actual weight was 65.5 % , with overestimate typically occurring by only 1 color zone . CONCLUSION The Broselow tape and APLS formula predict the weights of children in western Kenya . According to its better performance , ease of use , and provision of drug dosing and equipment size , the Broselow tape is superior to age-based formulas for estimation of weight in Kenyan children OBJECTIVES The Broselow pediatric emergency weight estimation tape is an accurate method of estimating children 's weights based on height-weight correlations and determining st and ardized medication dosages and equipment sizes using color-coded zones . The study objective was to determine the accuracy of the Broselow tape in the Indian pediatric population . METHODS The authors conducted a 6-week prospect i ve cross-sectional study of 548 children at a government pediatric hospital in Chennai , India , in three weight-based groups : < 10 kg ( n = 175 ) , 10 - 18 kg ( n = 197 ) , and > 18 kg ( n = 176 ) . Measured weight was compared to Broselow-predicted weight , and the percentage difference was calculated . Accuracy was defined as agreement on Broselow color-coded zones , as well as agreement within 10 % between the measured and Broselow-predicted weights . A cross-vali date d correction factor was also derived . RESULTS The mean percentage differences were -2.4 , -11.3 , and -12.9 % for each weight-based group . The Broselow color-coded zone agreement was 70.8 % in children weighing less than 10 kg , but only 56.3 % in the 10- to 18-kg group and 37.5 % in the > 18-kg group . Agreement within 10 % was 52.6 % for the < 10-kg group , but only 44.7 % for the 10- to 18-kg group and 33.5 % for the > 18-kg group . Application of a 10 % weight-correction factor improved the percentages to 77.1 % for the 10- to 18-kg group and 63.0 % for the > 18-kg group . CONCLUSIONS The Broselow tape overestimates weight by more than 10 % in Indian children > 10 kg . Weight overestimation increases the risk of medical errors due to incorrect dosing or equipment selection . Applying a 10 % weight-correction factor may be advisable |
11,237 | 25,520,140 | Laparoscopic surgery was associated with significantly lower intraoperative blood loss , earlier return of bowel movement and reduced length of hospital stay as compared to open surgery , although with increased operative time .
It also showed an obvious advantage for minimizing late complications of adhesion-related bowel obstruction .
On the basis of this meta- analysis we conclude that laparoscopic surgery has advantages of earlier postoperative recovery , less blood loss and lower rates of adhesion-related bowel obstruction .
In addition , oncological outcome is comparable after laparoscopic and open resection for rectal cancer | BACKGROUND AND AIM Laparoscopic and open rectum surgery for rectal cancer remains controversial .
This systematic review compared the short-term and long-term efficiency and complications associated with laparoscopic and open resection for rectal cancer . | Introduction The field of laparoscopic rectal cancer surgery is exp and ing . We compare short-term and early oncological outcomes after laparoscopic versus open resection in carefully matched rectal cancer patients . Methods All consecutive patients undergoing elective laparoscopic resection for rectal cancer were review ed . Laparoscopic resections were matched 1:1 to open resections by age , gender , American Society of Anesthesiologists class , body mass index , neoadjuvant chemoradiation , and type of surgery . Data were analyzed using Fisher ’s exact , chi-square , Wilcoxon rank-sum tests , and Kaplan – Meier estimates . P-value < 0.05 was considered statistically significant . Results Ninety-one rectal cancer patients with laparoscopic resection were included , 59 % were male , and median age was 62 years . Conversion rate was 18.7 % . Laparoscopic and open surgery had similar 30-day morbidity and mortality except wound infection , which was lower for the laparoscopic group ( p = 0.02 ) . Laparoscopic surgery had similar 30-day readmissions but shorter total length of hospital stay ( 5 versus 7 days , p < 0.01 ) , time to first flatus ( 3 versus 4.5 days , p = 0.001 ) , and time to first bowel movement ( 4 versus 5 days , p = 0.05 ) when compared with open surgery . The 3-year disease-free survival , local recurrence , and distant recurrence rates were also similar between the two groups . Conclusion Laparoscopic surgery can be safely performed for rectal cancer , with better postoperative recovery and acceptable early oncological outcomes . Results from large ongoing r and omized trials with longer follow-up time are pending to better define oncologic outcomes OBJECTIVE To assess the advantage and disadvantage of laparoscopic abdomino-perineal resection and open abdominoperineal resection for low rectal cancer . METHODS Patients with low rectal cancer , collected from July 2003 to April 2006 , were r and omly divided into laparoscopic abdominoperineal resection group ( 37 cases ) and open abdominoperineal resection group ( 37 cases ) . Operation time , number of lymph node removed , intra-operative blood loss , time to pass flatus , time to ambulate , time to discharge , complications , early recurrence , and economical cost were compared between the 2 groups . RESULTS All patients were performed successfully . For the first 10 patients , operation time of laparoscopic group was significantly longer than that of open group , but there was no significant difference between the 2 groups . Intra-operative blood loss of laparoscopic group was significantly less than that of open group , but it was reverse for the first 10 patients . There was no significant difference in time to pass flatus between the 2 groups . Time to ambulate in laparoscopic group was significantly earlier than that in open group . There was no significant difference in time to discharge between the 2 groups , but it was earlier for perineum closure in laparoscopic group . Relative complications of laparoscopic group , including pulmonary infection , abdominal wound infection or split , were significantly less than those of open group . There was no significant difference in number of lymph nodes removed , early recurrence between the 2 groups . Operation cost of laparoscopic group was significantly higher than that of open group , but there was no significant difference . CONCLUSION Advantages of laparoscopic abdominoperineal resection were characterized for not only minimal invasion and good cosmetic outcome but also less blood loss , complications , and earlier postoperative recovery . The operation time , total costs and oncological clearance of laparoscopic abdominoperineal resection patients were comparable with those of open procedure patients BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation . METHOD Twenty eight patients with distal rectal adenocarcinoma were r and omized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospect ively . Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach . RESULTS There was no significant difference ( p<0,05 ) between the two studied groups regarding : gender , age , body mass index , patients with previous abdominal surgeries , intra and post operative complications , need for blood transfusion , hospital stay after surgery , length of resected segment and pathological staging . Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach ( p=0.04 ) . Mean anesthesia duration was shorter ( p=0.03 ) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes , respectively . There was no need for conversion to open approach in this series . After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery , local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group . CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible , similar to conventional approach concerning surgery duration , intra operative morbidity , blood requirements and post operative morbidity . Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs A r and omized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer . Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively r and omized to either open or laparoscopic colorectal resection . Surgeons in 24 specialized institutions will recruit 818 patients . The primary end-point is overall survival . Secondary end-points are relapse-free survival , short-term clinical outcome , adverse events , the proportion of conversion from laparoscopic surgery to open surgery , and the proportion of completion of laparoscopic surgery The diagnosis of a lymph node-negative colorectal carcinoma should imply a good prognosis ; however , the outcomes for TNM stage II patients remain variable . Few studies have examined the relationship of the number of lymph nodes examined to the prognosis of this stage . The aim of this study was to determine whether the number of lymph nodes examined has an effect on prognosis of a relatively large sample of patients undergoing curative surgery for stage II colorectal cancer at a single institution . Data on patients who underwent surgery for colorectal cancer between January 1980 and April 2000 were prospect ively collected in a data base . Patients with TNM stage II or stage III tumours who were treated with curative intent were removed . Patients over 80 years of age were excluded from the survival analysis . Survival comparisons were made using Kaplan-Meier curves and the log-rank test . Multivariate analysis was performed using a Cox regression model . A total of 625 cases of TNM stage II cases and , for comparison purpose s , 415 stage III cases , were analysed . Lymph node retrieval in stage II cases was affected by the patient 's age ( P=0.04 ) and gender ( P=0.02 ) , tumour grade ( P<0.0001 ) , tumour site ( P<0.0001 ) , and necessity to carry out extended resection ( P<0.0001 ) . In stage III cases , lymph node retrieval was affected by patient age ( P<0.0001 ) , tumour grade ( P=0.02 ) , and tumour site ( P=0.002 ) . Decreased lymph node detection was associated with increasing hazard ratios among the 480 TNM stage II patients under 80 years of age , but not among the 345 patients with TNM stage III tumours . Five year survival rate for patients with stage III tumours with only 1 - 3 positive lymph nodes ( 52.6 % ) was similar to that of patients with stage II tumour who had nine or fewer lymph nodes examined ( 51.3 % ) . These results demonstrate that the prognosis of TNM stage II colorectal cancer is dependent on the number of lymph nodes examined . Patients with few nodes examined have a poorer prognosis . It is possible that a smaller number of lymph nodes examined reflects a diminished immune response . It can be presumed that those patients with stage II tumour with only a few nodes examined should be offered postoperative chemotherapy on a routine basis Background : Laparoscopic resection of the rectum is still under scrutiny for its adequacy of oncological clearance . Aim : To assess lymph node yield after laparoscopic total mesorectal excision ( TME ) for rectal cancer as compared to the open approach . Methods : 74 patients with middle and low rectal cancer were prospect ively r and omized in two groups . Group A included 39 patients who had an open TME ( 35 with low anterior resection of the rectum ( LARR ) and 4 with abdominoperineal resection of the rectum ( APR ) ) . In group B , there were 34 patients who had a laparoscopic TME ( 27 with LARR and 7 with APR ) . 10 of the LARR patients in group A and 14 of the LARR patients in group B had a defunctioning ileostomy . All operations were performed by one surgeon or under his supervision . Results : Gender and age distribution were similar for both groups ( group A : 23 males ; mean age 69 ( 41–85 ) ; group B : 20 males ; mean age 72 ( 31–84 ) ) . The mean distance of the tumor from the dentate line was 7.6 cm ( 1–12 cm ) for group A and 6.1 cm ( 1–12 cm ) for group B. Anastomosis was formed at a mean distance of 5.5 cm ( 1.5–8.5 cm ) from the dentate line in group A and 3.5 cm ( 1–4.5 cm ) in group B. At histology , in group A there were 5 T4 tumors , 9 T3 , 10 T3 + ( < 1 mm distance from the circumferential resection margin ) , 13 T2 and 2 T1 . In group B , there were 3 T4 tumors , 14 T3 , 8 T3 + , 7 T2 and 2 T1 . Differences between groups were not significant . The mean number of lymph nodes retrieved in group A specimens was 19.2 ( 5–45 ) and in group B 19.2 ( 8–41 ) ( p = 0.2 ) . In group A , 3.9 ( 1–9 ) regional , 13.9 ( 3–34 ) intermediate and 1.5 ( 1–3 ) apical lymph nodes were retrieved . The respective values in group B were 3.7 ( 3–7 ) , 14.4 ( 4–33 ) and 1.3 ( 1–3 ) . Differences between groups were not significant . Also , the incidence of lymph node involvement by the tumor was not significantly different between groups ( group A : 23 ; group B : 19 ) . Conclusions : Laparoscopic resection of the rectum can achieve similar lymph node clearance to the open approach . Also , distribution of the lymph nodes along the resected specimens is similar between the two approaches Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization INTRODUCTION Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a r and omized clinical trial . TRIAL DESIGN Non-inferiority r and omized clinical trial . METHODS The COLOR II trial is an ongoing international r and omized clinical trial . Currently 27 hospitals from Europe , South Korea and Canada are including patients . The primary endpoint is loco-regional recurrence rate three years post-operatively . Secondary endpoints cover quality of life , overall and disease free survival , post-operative morbidity and health economy analysis . RESULTS By July 2008 , 27 hospitals from the Netherl and s , Belgium , Germany , Sweden , Spain , Denmark , South Korea and Canada had included 739 patients . The intra-operative conversion rate in the laparoscopic group was 17 % . Distribution of age , location of the tumor and radiotherapy were equal in both treatment groups . Most tumors are located in the mid-rectum ( 41 % ) . CONCLUSION Laparoscopic surgery in the treatment of rectal cancer is feasible . The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown , but are subject of interim analysis within the COLOR II trial . Completion of inclusion is expected by the end of 2009 . TRIAL REGISTRATION Clinical trials.gov , identifier : NCT00297791 ( www . clinical trials.gov ) Local recurrence after resection for rectal cancer remains common despite growing acceptance that inadequate local excision may be implicated . In a prospect i ve study of 190 patients with rectal cancer , we examined the circumferential margin of excision of resected specimens for tumour presence , to examine its frequency and its relation to subsequent local recurrence . Tumour involvement of the circumferential margin was seen in 25 % ( 35/141 ) of specimens for which the surgeon thought the resection was potentially curative , and in 36 % ( 69/190 ) of all cases . After a median 5 years ' follow-up ( range 3.0 - 7.7 years ) , the frequency of local recurrence after potentially curative resection was 25 % ( 95 % CI 18 - 33 % ) . The frequency of local recurrence was significantly higher for patients who had had tumour involvement of the circumferential margin than for those without such involvement ( 78 [ 95 % CI 62 - 94 ] vs 10 [4 - 16]% ) . By Cox 's regression analysis tumour involvement of the circumferential margin independently influenced both local recurrence ( hazard ratio = 12.2 [ 4.4 - 34.6 ] ) and survival ( 3.2 [ 1.6 - 6.53 ] ) . These results show the importance of wide local excision during resection for rectal cancer , and the need for routine assessment of the circumferential margin to assess prognosis Despite improved surgical treatment strategies for rectal cancer , 5–15 % of all patients will develop local recurrences . After conservative surgery , circumferential resection margin ( CRM ) involvement is a strong predictor of local recurrence . The consequences of a positive CRM after total mesorectal excision ( TME ) have not been evaluated in a large patient population . In a nationwide r and omized multicenter trial comparing preoperative radiotherapy and TME versus TME alone for rectal cancer , CRM involvement was determined according to trial protocol . In this study we analyze the criteria by which the CRM needs to be assessed to predict local recurrence for nonirradiated patients ( n = 656 , median follow-up 35 months ) . CRM involvement is a strong predictor for local recurrence after TME . A margin of ≤2 mm is associated with a local recurrence risk of 16 % compared with 5.8 % in patients with more mesorectal tissue surrounding the tumor ( p < 0.0001 ) . In addition , patients with margins ≤1 mm have an increased risk for distant metastases ( 37.6 % vs 12.7 % , p < 0.0001 ) as well as shorter survival . The prognostic value of CRM involvement is independent of TNM classification . Accurate determination of CRM in rectal cancer is important for determination of local recurrence risk , which might subsequently be prevented by additional therapy . In contrast to earlier studies , we show that an increased risk is present when margins are ≤2 mm PURPOSE The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial . Results from r and omized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term . Few data are available on rectal cancer , and long-term data on survival and recurrence are now required . METHODS The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer ( UK MRC CLASICC ; clinical trials number IS RCT N 74883561 ) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum . The r and omization ratio was 2:1 in favor of laparoscopic surgery . Long-term outcomes ( 3-year overall survival [ OS ] , disease-free survival [ DFS ] , local recurrence , and quality of life [ QoL ] ) have now been determined on an intention-to-treat basis . RESULTS Seven hundred ninety-four patients were recruited ( 526 laparoscopic and 268 open ) . Overall , there were no differences in the long-term outcomes . The differences in survival rates were OS of 1.8 % ( 95 % CI , -5.2 % to 8.8 % ; P = .55 ) , DFS of -1.4 % ( 95 % CI , -9.5 % to 6.7 % ; P = .70 ) , local recurrence of -0.8 % ( 95 % CI , -5.7 % to 4.2 % ; P = .76 ) , and QoL ( P > .01 for all scales ) . Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection ( AR ) , but it did not translate into an increased incidence of local recurrence . CONCLUSION Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR , and support the continued use of laparoscopic surgery in these patients PURPOSE : We have previously reported the five-year results of a r and omized trial comparing laparoscopic and open resection for cancer of the upper rectum and rectosigmoid junction . The aim of this follow-up study is to report on the long-term morbidity and ten-year oncologic outcomes among the subgroup of patients with upper rectal cancer . METHODS : From September 1993 to October 2002 , 153 patients with upper rectal cancer were r and omly assigned to receive either laparoscopic-assisted ( n = 76 ) or open ( n = 77 ) anterior resection . Patients were last followed up in December 2007 . Long-term morbidity , survival , and disease-free interval were prospect ively recorded . Data were analyzed by intention-to-treat principle . RESULTS : The demographic data of the two groups were comparable . More patients in the open group developed adhesion-related bowel obstruction requiring hospitalization ( P = 0.001 ) and intervention . The overall long-term morbidity rate was also significantly higher in the open group ( P = 0.012 ) . After curative resection , the probabilities of cancer-specific survival at ten years of the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent , respectively ( P = 0.595 ) , and their probabilities of being disease-free at ten years were 82.9 percent and 80.4 percent , respectively ( P = 0.698 ) . CONCLUSION : Laparoscopic-assisted anterior resection for upper rectal cancer is associated with fewer long-term complications and similar ten-year oncologic outcomes when compared with open surgery BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent Background Laparoscopic resection of colonic cancer has been shown to improve postoperative recovery without jeopardizing tumor clearance and survival , but information on low rectal cancer is scarce . The aim of this r and omized trial was to compare postoperative recovery between laparoscopic-assisted versus open abdominoperineal resection ( APR ) in patients with low rectal cancer . Recurrence and survival data were also recorded and compared between the two groups . Methods Between September 1994 and February 2005 , 99 patients with low rectal cancer were r and omized to receive either laparoscopic-assisted ( 51 patients ) or conventional open ( 48 patients ) APR . The median follow-up time of living patients was about 90 months for both groups . The primary and secondary endpoints of the study were postoperative recovery and survival , respectively . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with earlier return of bowel function ( P < .001 ) and mobilization ( P = .005 ) , and less analgesic requirement ( P = .007 ) . This was at the expense of longer operative time and higher direct cost . There were no differences in morbidity and operative mortality rates between the two groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 75.2 % and 76.5 % respectively ( P = .20 ) . The respective probabilities of being disease-free were 78.1 % and 73.6 % ( P = .55 ) . Conclusions Laparoscopic-assisted APR improves postoperative recovery and seemingly does not jeopardize survival when compared with open surgery for low rectal cancer . A larger sample size is needed to fully assess oncological outcomes BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
11,238 | 28,767,390 | Our meta- analysis has found the haplotype of TGFB1 codon 10/25 T/T G/G and T/C G/G genotypes , associated with increased production of TGF-β1 , was linked with CAD risk following kidney transplantation .
Moreover , no significant difference was found between TGFB1 codon 10 or codon 25 and the development of CAD | BACKGROUND Epidemiological studies have investigated the role of transforming growth factor-β1 ( TGF-β1 ) in chronic allograft dysfunction ( CAD ) following kidney transplantation .
TGFB1 gene polymorphisms ( SNP rs1800470 and rs1800471 ) may be associated with the risk of CAD .
In this meta- analysis , the relationship between these two variations and the risk of CAD was explored . | Little is known about the involvement of saliva in gingival overgrowth ( GO ) . It was hypothesized that , in this situation , the composition of saliva is altered . Thus , proteins , albumin , cytokines , and growth factors in whole and gl and ular saliva were investigated . Differences between gl and ular and gingival contributions to the composition of saliva were explored in patients medicated with cyclosporin who exhibited GO ( responders ) , those without GO ( non-responders ) , and non-medicated subjects ( controls ) . In whole saliva , interleukin-1α ( IL-1α ) , IL-6 , IL-8 , epidermal growth factor ( EGF ) , nerve growth factor ( NGF ) , and albumin were detected , but in gl and ular saliva only EGF and NGF were identified . Albumin and IL-6 differed significantly between responders and controls , although the overall profile of salivary proteins remained unchanged . Thus , inflammatory cytokines and albumin are confined to whole saliva and are associated with GO , whereas its content of EGF and NGF appears unaffected by cyclosporin Transforming growth factor-beta 1 ( TGF-beta 1 ) plays an important role in the modulation of cellular growth and differentiation and the production and degradation of the extracellular matrix . A number of experimental results suggest that TGF-beta 1 may be involved in cardiovascular physiopathology . In the present study , we assessed whether the TGF-beta 1 gene is a c and i date gene for coronary heart disease or hypertension . We screened the coding region and 2181 bp upstream of the TGF-beta gene for polymorphisms and identified seven polymorphisms : 3 in the upstream region of the gene at positions -988 , -800 , and -509 from the first transcribed nucleotide ; 1 in a nontranslated region at position + 72 ; 2 in the signal peptide sequence Leu10 - ->Pro , Arg25 - ->Pro ; and 1 in the region of the gene coding for the precursor part of the protein not present in the active form , Thr263 - ->Ile . We analyzed these TGF-beta 1 polymorphisms in 563 patients with myocardial infa rct ion and 629 control subjects from four regions in Northern Irel and and France . The Pro25 allele was more frequent in patients than in control subjects in Belfast ( P < .01 ) and Strasbourg ( P < .05 ) . The TGF-beta 1 polymorphisms were not associated with the degree of angiographically assessed coronary artery disease in patients . The presence of a Pro25 allele was associated with a lower systolic pressure in the four control groups ( P < .002 ) , and a history of hypertension was significantly less frequent in homozygotes or heterozygotes for Pro25 than in hormozygotes for Arg25 ( odds ratio , 0.43 , 95 % confidence interval , 0.19 to 0.92 ; P < .03 ) . Since the Pro25 allele was associated with an increased risk of myocardial infa rct ion and a reduced risk of hypertension , we favor a cautious interpretation of these apparently inconsistent results . Other studies will need to verify whether these associations are real |
11,239 | 30,506,484 | Conclusions The best current evidence indicates that Gla-300 reduces the incidence of nocturnal hypoglycemia with slight improvements in glycemic control compared with Gla-100 in both type 1 and type 2 diabetes adult patients | Aims To assess the effectiveness of insulin glargine 300 ui/ml ( Gla-300 ) compared with insulin glargine 100 ui/ml ( Gla-100 ) on reducing nocturnal hypoglycemia and improving glycemic control in type 1 and type 2 diabetes patients . | To compare the efficacy and safety of new insulin glargine 300 U/ml ( Gla‐300 ) with insulin glargine 100 U/ml ( Gla‐100 ) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs ( OADs ) AIM To explore if efficacy and safety findings for insulin glargine 300U/mL ( Gla-300 ) versus insulin glargine 100U/mL ( Gla-100 ) , observed over 6 months in insulin-naïve people with type 2 diabetes , are maintained after 12 months . METHODS EDITION 3 was a phase 3a , r and omized , multicentre , open-label , parallel-group , treat-to-target study of once-daily Gla-300 versus Gla-100 ( target fasting self-monitored plasma glucose , 4.4 - 5.6mmol/L [ 80 - 100mg/dL ] ) . Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin . RESULTS Of 878 participants r and omized , 337/439 ( 77 % ) and 314/439 ( 72 % ) assigned to Gla-300 and Gla-100 , respectively , completed 12 months of treatment . Improved glycaemic control was sustained until 12 months in both treatment groups , with similar reductions in HbA1c from baseline to month 12 ( difference : -0.08 [ 95 % confidence interval ( CI ) : -0.23 to 0.07 ] % or -0.9 [ -2.5 to 0.8 ] mmol/mol ) . Relative risk of experiencing≥1 confirmed ( ≤3.9mmol/L [ ≤70mg/dL ] ) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 ( 95 % CI : 0.69 to 1.07 ) at night and 0.92 ( 0.82 to 1.03 ) at any time of day . For events with a glycaemic threshold of<3.0mmol/L ( < 54mg/dL ) these numbers were 0.76 ( 0.49 to 1.19 ) and 0.66 ( 0.50 to 0.88 ) . A similar pattern was seen for documented symptomatic events . No between-group differences in adverse events were identified . CONCLUSION Over 12 months , Gla-300 treatment was as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes , with lower overall risk of hypoglycaemia at the<3.0mmol/L threshold Aims To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml ( Gla-300 ) versus glargine 100 U/ml ( Gla-100 ) in people with type 2 diabetes mellitus ( T2DM ) using basal plus meal-time insulin for 12 months in the EDITION 1 trial . Methods EDITION 1 was a multicentre , r and omized , open-label , two-arm , phase IIIa study . Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100 , as previously r and omized , once daily for a further 6-month open-label extension phase . Changes in glycated haemoglobin ( HbA1c ) and fasting plasma glucose concentrations , insulin dose , hypoglycaemic events and body weight were assessed . Results Of 807 participants enrolled in the initial phase , 89 % ( 359/404 ) assigned to Gla-300 and 88 % ( 355/403 ) assigned to Gla-100 completed 12 months . Glycaemic control was sustained in both groups ( mean HbA1c : Gla-300 , 7.24 % ; Gla-100 , 7.42 % ) , with more sustained HbA1c reduction for Gla-300 at 12 months : least squares mean difference Gla-300 vs Gla-100 : HbA1c −0.17 [ 95 % confidence interval ( CI ) −0.30 to −0.05]% . The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100 . Lower percentages of participants had ≥1 confirmed [ ≤3.9 mmol/l ( ≤70 mg/dl ) ] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [ 24 h ; 86 vs 92 % ; relative risk 0.94 ( 95 % CI 0.89–0.99 ) ] and during the night [ 54 vs 65 % ; relative risk 0.84 ( 95 % CI 0.75–0.94 ) ] , while the annualized rates of such hypoglycaemic events were similar . No between-treatment differences in adverse events were apparent . Conclusion During 12 months of treatment of T2DM requiring basal and meal-time insulin , glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100 . The mean basal insulin dose was higher with Gla-300 compared with Gla-100 , but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments Abstract Introduction New insulin glargine 300 U mL−1 ( Gla-300 ) is a basal insulin that shows more stable and prolonged pharmacokinetic and pharmacodynamic profiles than insulin glargine 100 U mL−1 ( Gla-100 ) . This study used continuous glucose monitoring ( CGM ) to compare 24-h glucose profiles in a Japanese population using Gla-300 versus Gla-100 . Methods This was an exploratory 8.4-week , single-center , 2-sequence , 2-period , open-label crossover study . Japanese adults with type 1 diabetes mellitus ( T1DM ) treated with basal – bolus insulin , with glycated hemoglobin ( HbA1c ) 6.5–10.0 % and median fasting self-monitored plasma glucose concentration ≤13 mmol L−1 , were r and omized to Gla-300 followed by Gla-100 ( subgroup 1 ) or vice versa ( subgroup 2 ) , with no washout period . CGM was performed on the last 3 days of the screening period and each treatment period . Primary endpoint was comparison of 24-h glucose variability ( area under the curve [AUC]mean_24 h ) on the second day of each CGM measurement with Gla-300 versus Gla-100 . Baseline and end of treatment period values for HbA1c , fasting plasma glucose ( FPG ) and daily basal/mealtime insulin doses were recorded . Hypoglycemia and adverse events ( AEs ) were recorded . Results Twenty participants were r and omized ( 10 to subgroup 1 and 10 to subgroup 2 ) . Participants showed comparable glucose variability over 24 h ( AUCmean_24 h during treatment with Gla-300 or Gla-100 ( treatment ratio 0.96 ; 90 % confidence interval 0.79 , 1.16 ) . HbA1c and FPG were generally stable across both treatment periods . There was a trend towards fewer participants experiencing ≥1 hypoglycemia event at any time ( 24 h ) and at night ( 00:00–05:59 h ) with Gla-300 versus Gla-100 . Treatment-emergent AEs , reported by 9/20 ( 45 % ) and 4/20 ( 20 % ) participants during Gla-300 and Gla-100 treatment , respectively , were unrelated to study medication . Conclusions In this cohort of Japanese people with T1DM , no between-treatment difference was observed in glucose variability with Gla-300 versus Gla-100 , as measured by CGM . There was a trend for less hypoglycemia with Gla-300 , particularly at night , versus Gla-100 . Both treatments were well tolerated . Funding Sanofi , Tokyo , Japan . Clinical trial registration : NCT01676233 , 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 Aims Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) profiles of new insulin glargine 300 U/ml ( Gla-300 ) and insulin glargine 100 U/ml ( Gla-100 ) in people with type 1 diabetes mellitus . Methods In two double-blind , r and omized , crossover studies , 18 Japanese participants ( aged 20–65 years ) and 24 European participants ( aged 18–65 years ) with glycated haemoglobin levels ≤9.0 % ( ≤75 mmol/mol ) received single subcutaneous doses of Gla-300 , 0.4 , 0.6 and 0.9 U/kg ( 0.9 U/kg in the European study only ) , and Gla-100 , 0.4 U/kg . A 36-h euglycaemic clamp procedure was performed after each dosing . Results The serum insulin glargine concentration ( INS ) and glucose infusion rate ( GIR ) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100 . In support of this , the times to 50 % of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period , indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose . Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300 . Conclusions Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100 , maintaining blood glucose control for up to 36 h in euglycaemic clamp setting s in Japanese and European participants with type 1 diabetes AIMS Data on the impact of hypoglycaemia on patients ' daily lives and diabetes self-management , particularly in developing countries , are lacking . The aim of this study was to assess fear of , and responses to , hypoglycaemia experienced by patients globally . MATERIAL S AND METHODS This non-interventional , multicentre , 4-week prospect i ve study using self- assessment question naires and patient diaries consisted of 27,585 patients , ≥18years , with type 1 diabetes ( n=8022 ) or type 2 diabetes ( n=19,563 ) treated with insulin for > 12months , at 2004 sites in 24 countries worldwide . RESULTS Increased blood glucose monitoring ( 69.7 % ) and seeking medical assistance ( 62.0 % ) were the most common responses in the 4weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes , respectively . Approximately 44 % of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode . Following hypoglycaemia , 3.9 % ( type 1 diabetes ) and 6.2 % ( type 2 diabetes ) of patients took leave from work or study . Regional differences in fear of , and responses to , hypoglycaemia were evident - in particular , a lower level of hypoglycaemic fear and utilisation of healthcare re sources in Northern Europe and Canada . CONCLUSIONS Hypoglycaemia has a major impact on patients and their behaviour . These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies Aims Insulin glargine 300 U/mL ( Gla‐300 ) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL ( Gla‐100 ) . We have compared these insulins over 1 year in people with type 1 diabetes ( T1DM ) . Methods EDITION 4 was a 6‐month , multicentre , r and omized , open‐label phase 3 study . People with T1DM who completed the 6 months continued r and omized Gla‐300 or Gla‐100 once daily , morning or evening , for a further 6 months . Results Among 549 participants r and omized , 444 completed the 12‐month study period ( Gla‐300 , 80 % ; Gla‐100 , 82 % ) . Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups ( difference , 0.02 [ 95 % CI , −0.13 to 0.17 ] ) % ‐units [ 0.2 ( −1.5 to 1.9 ) mmol/mol ] ) , to a mean of 7.86 % ‐units ( 62.4 mmol/mol ) in both groups . For morning vs evening injection , there was no difference in HbA1c change over 12 months for Gla‐100 , but a significantly larger decrease in HbA1c was observed in the Gla‐300 morning group than in the Gla‐300 evening group ( difference , −0.25 [ −0.47 to −0.04 ] % ‐units [ −2.7 ( −5.2 to −0.4 ) mmol/mol ] ) . Mean glucose from the 8‐point SMPG profiles decreased from baseline , and was similar between the 2 treatment groups . Basal insulin dose was 20 % higher with Gla‐300 than with Gla‐100 , while hypoglycaemia event rates , analysed at night , over 24 hours , or according to different glycaemic thresholds , did not differ between treatment groups , regardless of injection time . Adverse event profiles did not differ between groups . Conclusions In T1DM , Gla‐300 provides glucose control comparable to that of Gla‐100 , and can be given at any time of day AIMS To evaluate the efficacy and safety of insulin glargine 300U/mL ( Gla-300 ) versus glargine 100U/mL ( Gla-100 ) in adults with type 1 diabetes in Japan over 12months . METHODS EDITION JP 1 was a multicentre , r and omised , open-label phase 3 study . Following a 6-month on-treatment period , participants continued to receive Gla-300 or Gla-100 once daily , plus mealtime insulin , over a 6-month open-label extension phase . HbA1c , hypoglycaemia , body weight and adverse events were assessed . RESULTS Overall , 114/122 ( 93 % ) and 114/121 ( 94 % ) of participants in the Gla-300 and Gla-100 group , respectively , completed the 6-month extension phase . Glycaemic control was sustained in both groups up to month 12 ( mean HbA1c : Gla-300 , 7.9 % [ 62mmol/mol ] ; Gla-100 , 7.8 % [ 62mmol/mol ] ) . Annualised rates of hypoglycaemia were lower with Gla-300 versus Gla-100 ; significantly for nocturnal confirmed ( < 3.0mmol/L [ < 54mg/dL ] ) or severe hypoglycaemia ( 2.39 and 3.85 events per participant-year ; rate ratio : 0.62 [ 0.39 - 0.97 ] ) . No between-treatment differences in mean body weight change or adverse events were observed . CONCLUSION Over 12months ' treatment , participants with type 1 diabetes receiving Gla-300 achieved sustained glycaemic control and experienced less nocturnal hypoglycaemia that was confirmed ( < 3.0mmol/L [ < 54mg/dL ] ) or severe compared with Gla-100 , supporting the 6-month results OBJECTIVE SENIOR compared the efficacy and safety of insulin glargine 300 units/mL ( Gla-300 ) with glargine 100 units/mL ( Gla-100 ) in older people ( ≥65 years old ) with type 2 diabetes . RESEARCH DESIGN AND METHODS SENIOR was an open-label , two-arm , parallel-group , multicenter phase 3b trial design ed to enroll ∼20 % of participants aged ≥75 years . Participants were r and omized 1:1 to Gla-300 or Gla-100 , titrated to a fasting self-monitored plasma glucose of 5.0–7.2 mmol/L ( 90–130 mg/dL ) . RESULTS In total , 1,014 participants were r and omized ( mean age : 71 years ) . Comparable reductions in HbA1c were observed from baseline to week 26 for Gla-300 ( −0.89 % ) and Gla-100 ( −0.91 % ) in the overall population ( least squares mean difference : 0.02 % [ 95 % CI −0.092 to 0.129 ] ) and for participants aged ≥75 years ( −0.11 % [ −0.330 to 0.106 ] ) . Incidence and rates of confirmed ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) or severe hypoglycemia events were low and similar between both treatment groups , with lower rates of documented symptomatic hypoglycemia with Gla-300 . The lower risk of hypoglycemia with Gla-300 versus Gla-100 was more apparent in the subgroup aged ≥75 years versus the overall population . Significantly lower annualized rates of documented symptomatic ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) hypoglycemia were observed ( Gla-300 : 1.12 ; Gla-100 : 2.71 ; rate ratio : 0.45 [ 95 % CI 0.25–0.83 ] ) . CONCLUSIONS Efficacy and safety of Gla-300 was demonstrated in older people ( ≥65 years of age ) with type 2 diabetes , with comparable reductions in HbA1c and similarly low or lower risk of documented symptomatic hypoglycemia versus Gla-100 . A significant benefit in hypoglycemia reduction was seen in participants aged ≥75 years AIMS To compare insulin glargine 300 U/mL ( Gla-300 ) with glargine 100 U/mL ( Gla-100 ) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months . METHODS EDITION JP 2 was a r and omised , open-label , phase 3 study . Following a 6-month treatment period , participants continued receiving previously assigned once daily Gla-300 or Gla-100 , plus oral anti-hyperglycaemic drugs , in a 6-month extension period . Glycaemic control , hypoglycaemia and adverse events were assessed . RESULTS The 12-month completion rate was 88 % for Gla-300 and 96 % for Gla-100 , with comparable reasons for discontinuation . Mean HbA1c decrease from baseline to month 12 was 0.3 % in both groups . Annualised rates of confirmed ( ≤3.9mmol/L [ ≤70mg/dL ] ) or severe hypoglycaemia were lower with Gla-300 than Gla-100 ( nocturnal [ 00:00 - 05:59h ] : rate ratio 0.41 ; 95 % confidence interval : 0.18 to 0.92 ; anytime [ 24h ] : rate ratio 0.64 ; 95 % confidence interval : 0.44 to 0.94 ) . Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100 . Adverse event profiles were comparable between treatments . CONCLUSION Over 12 months , Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia , particularly at night , versus Gla-100 , supporting 6-month results OBJECTIVE To characterize the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of a new insulin glargine comprising 300 units·mL−1 ( Gla-300 ) , compared with insulin glargine 100 units·mL−1 ( Gla-100 ) at steady state in people with type 1 diabetes . RESEARCH DESIGN AND METHODS A r and omized , double-blind , crossover study ( N = 30 ) was conducted , applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study , participants received once-daily subcutaneous administrations of either 0.4 ( cohort 1 ) or 0.6 units·kg−1 ( cohort 2 ) Gla-300 for 8 days in one treatment period and 0.4 units·kg−1 Gla-100 for 8 days in the other . Here we focus on the results of a direct comparison between 0.4 units·kg−1 of each treatment . PK and PD assessment s performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. RESULTS At steady state , insulin concentration ( INS ) and glucose infusion rate ( GIR ) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer , as supported by the later time ( ∼3 h ) to 50 % of the area under the serum INS and GIR time curves from time zero to 36 h post dosing . Tight blood glucose control ( ≤105 mg·dL−1 ) was maintained for approximately 5 h longer ( median of 30 h ) with Gla-300 compared with Gla-100 . CONCLUSIONS Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100 , extending blood glucose control well beyond 24 OBJECTIVE The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL ( Gla-300 ) or glargine 100 units/mL ( Gla-100 ) in the morning or evening , in combination with mealtime insulin . RESEARCH DESIGN AND METHODS In this 16-week , exploratory , open-label , parallel-group , two-period crossover study ( clinical trials.gov identifier NCT01658579 ) , 59 adults with type 1 diabetes were r and omized ( 1:1:1:1 ) to once-daily Gla-300 or Gla-100 given in the morning or evening ( with crossover in the injection schedule ) . The primary efficacy end point was the mean percentage of time in the target glucose range ( 80–140 mg/dL ) , as measured using continuous glucose monitoring ( CGM ) , during the last 2 weeks of each 8-week period . Additional end points included other CGM glycemic control parameters , hypoglycemia ( per self-monitored plasma glucose [ SMPG ] ) , and adverse events . RESULTS The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups . There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 ( least squares mean difference −14.7 mg/dL [ 95 % CI −26.9 to −2.5 ] ; P = 0.0192 ) . Mean 24-h glucose curves for the Gla-300 group were smoother ( lower glycemic excursions ) , irrespective of morning or evening injection . Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100 . Nocturnal confirmed ( < 54 mg/dL by SMPG ) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants ( 4.0 vs. 9.0 events per participant-year ; rate ratio 0.45 [ 95 % CI 0.24–0.82 ] ) . CONCLUSIONS Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval , smoother average 24-h glucose profiles irrespective of injection time , and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100 |
11,240 | 31,233,569 | This improvement on HRQoL was associated to interventions on " Case Management " and " Treatments and Procedures " , which were based on a theory , were of shorter duration , and had a follow-up period .
Interventions targeting people with chronic diseases result ed in a slight increase in the HRQoL that was not always significant , which suggests that there is a need for their continuous improvement | PURPOSE The objective of this systematic review was to determine the characteristics of the interventions conducted by nurses that attempt to improve the health related quality of life ( HRQoL ) of people over 18 years of age with chronic diseases . | BACKGROUND There has been limited study of yoga training as a complementary exercise strategy to manage the symptom of dyspnea in patients with chronic obstructive pulmonary disease ( COPD ) . PURPOSE The primary purpose of this pilot study was to evaluate a yoga program for its safety , feasibility , and efficacy for decreasing dyspnea intensity ( DI ) and dyspnea-related distress ( DD ) in older adults with COPD . METHODS Clinical ly stable patients with COPD ( n = 29 ; age 69.9 + /- 9.5 ; forced expiratory volume in 1 second ( FEV(1 ) ) 47.7 + /- 15.6 % predicted ; female = 21 ) were r and omized to a 12-week yoga program specifically design ed for people with COPD or usual-care control ( UC ) . The twice-weekly yoga program included asanas ( yoga postures ) and visama vritti pranayama ( timed breathing ) . Safety measure outcomes included heart rate , oxygen saturation , dyspnea , and pain . Feasibility was measured by patient-reported enjoyment , difficulty , and adherence to yoga sessions . At baseline and at 12 weeks , DI and DD were measured during incremental cycle ergometry and a 6-minute walk ( 6MW ) test . Secondary efficacy outcomes included physical performance , psychologic well-being , and health-related quality of life ( HRQoL ) . RESULTS Yoga training was safe and feasible for patients with COPD . While yoga training had only small effects on DI after the 6MW test ( effect size [ ES ] , 0.20 ; p = 0.60 ) , there were greater reductions in DD in the yoga group compared to UC ( ES , 0.67 ; p = 0.08 ) . Yoga training also improved 6MW distance ( + 71.7 + /- 21.8 feet versus -27.6 + /- 36.2 feet ; ES = 0.78 , p = 0.04 ) and self-reported functional performance ( ES = 0.79 , p = 0.04 ) compared to UC . There were small positive changes in muscle strength and HRQoL. CONCLUSIONS Elderly patients with COPD participated safely in a 12-week yoga program especially design ed for patients with this chronic illness . After the program , the subjects tolerated more activity with less DD and improved their functional performance . These findings need to be confirmed in a larger , more sufficiently powered efficacy study BACKGROUND Heart failure ( HF ) is a major public health problem . Case management by nurses using telephone follow-up has been suggested as a convenient and effective mechanism to promote the self-management of HF . Similarly , a patient empowerment approach to the management of chronic disease has been suggested as one that may nurture self-management in individuals with chronic illness . OBJECTIVE The purpose of this study was to examine the effects of a telephone-delivered empowerment intervention ( EI ) on clinical ly and theoretically relevant outcomes in patients with HF , including purpose ful participation in goal attainment , self-management of HF , and perception of functional health . The EI was guided by Rogers ' Science of Unitary Human Beings person-environment process . METHODS A convenience sample of men and women aged 21 years and older with a clinical diagnosis of HF was obtained from a metropolitan hospital located in the southwestern United States . The participants were r and omly assigned to the control group ( n = 45 ) or EI group ( n = 45 ) . All participants received st and ardized HF patient education ; the intervention group also received an EI delivered through telephone follow-up calls from a registered nurse . Repeated- measures analysis of variance was used to evaluate intervention effects . RESULTS The telephone-delivered EI facilitated self-management of HF through self-care activities in EI group members . CONCLUSION The knowledge gained from this study provides a beginning underst and ing of strategies to enhance health care providers ' ability to facilitate self-management of HF among patients diagnosed with HF Objectives To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease ( COPD ) . Design Cluster r and omised controlled trial . Setting Tasmanian general practice s : capital city ( 11 ) , large rural ( 3 ) , medium rural ( 1 ) and small rural ( 16 ) . Participants Patients were invited ( 1207 ) from general practitioner ( GP ) data bases with COPD diagnosis and /or tiotropium prescription , response rate 49 % ( 586 ) , refused ( 176 ) and excluded ( criteria : smoking history or previous study , 68 ) . Spirometry testing ( 342 ) confirmed moderate or severe COPD in 182 ( 53 % ) patients . R and omisation By r and om numbers code , block stratified on location , allocation by sequentially numbered , opaque and sealed envelopes . Intervention Health mentor ( HM ) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting : problem solving , decision-making and action planning . Control : usual care ( UC ) group received GP care plus non-interventional brief phone calls . Outcomes Measured at 0 , 6 and 12 months , the Short Form 36 ( SF-36 ) and St George ’s Respiratory Question naire ( SGRQ , primary ) ; Partners In Health ( PIH ) Scale for self-management capacity , Hospital Anxiety and Depression Scale ( HADS ) , Center for Epidemiologic Studies -Depression ( CES-D ) question naire , Post-Traumatic Stress Disorder Checklist , Satisfaction with life and hospital admissions ( secondary ) . Results 182 participants with COPD ( age 68±8 years , 62 % moderate COPD and 53 % men ) were r and omised ( HM=90 and UC=92 ) . Mixed model regression analysis accounting for clustering , adjusting for age , gender , smoking status and airflow limitation assessed efficacy ( regression coefficient , β , reported per 6-month visit ) . There was no difference in quality of life between groups , but self-management capacity increased in the HM group ( PIH overall 0.15 , 95 % CI 0.03 to 0.29 ; knowledge domain 0.25 , 95 % CI 0.00 to 0.50 ) . Anxiety decreased in both groups ( HADS A 0.35 ; 95 % CI −0.65 to −0.04 ) and coping capacity improved ( PIH coping 0.15 ; 95 % CI 0.04 to 0.26 ) . Conclusions Health mentoring improved self-management capacity but not quality of life compared to regular phone contact , which itself had positive effects where decline is generally expected OBJECTIVE Women with gynecological cancers have reported poor health-related quality of life ( QOL ) , with complex physical and psychological needs post-surgery and during chemotherapy treatment . There are no studies reporting interventions addressing these needs post-hospital discharge in this population . METHODS Patients were r and omized into two groups . The intervention group received 6 months of specialized care by an Advanced Practice Nurse ( APN ) ; in addition , women with high distress were evaluated and monitored by a psychiatric consultation-liaison nurse ( PCLN ) . The attention control group was assisted with symptom management by a research assistant . The effects of the 6-month intervention were evaluated using self-report question naires at baseline ( 24 - 48 h after surgery ) , 1 , 3 , and 6 months post- surgery . QOL assessment s included the Center for Epidemiological Studies -Depression Scale , the ambiguity subscale of the Mishel Uncertainty in Illness Scale , the Symptom Distress Scale , and the Short-Form Health Survey ( SF-12 ) . The sample for the longitudinal analysis included 123 who completed QOL outcome measures across three occasions post-surgery . RESULTS The APN intervention result ed in significantly less uncertainty than the attention control intervention 6 months after surgery . When the sub-group who received the APN plus PCLN intervention was compared with the total attention control group , the sub-group had significantly less uncertainty , less symptom distress , and better SF-12 mental and physical QOL over time . CONCLUSION Nurse tailored interventions that target both physical and psychological aspects of QOL in women recovering from cancer surgery and undergoing chemotherapy produce stronger outcomes than interventions that target solely one QOL aspect Aim To examine the effects of a nurse-led case management programme for hospital-discharged older adults with co-morbidities . Background The most significant chronic conditions today involve diseases of the cardiovascular , respiratory , endocrine and renal systems . Previous studies have suggested that a nurse-led case management approach using either telephone follow-ups or home visits was able to improve clinical and patient outcomes for patients having a single , chronic disease , while the effects for older patients having at least two long-term conditions are unknown . A self-help programme using motivation and empowerment approaches is the framework of care in the study . Design R and omized controlled trial . Method The study was conducted from 2010–2012 . Older patients having at least two chronic diseases were included for analysis . The participants were r and omized into three arms : two study groups and one control group . Data were collected at baseline and at 4 and 12 weeks later . Results Two hundred and eighty-one patients completed the study . The interventions demonstrated significant differences in hospital readmission rates within 84 days post discharge . The two intervention groups had lower readmission rates than the control group . Patients in the two study arms had significantly better self-rated health and self-efficacy . There was significant difference between the groups in the physical composite score , but no significant difference in mental component score in SF-36 scale . Conclusion The postdischarge interventions led by the nurse case managers on self-management of disease using the empowerment approach were able to provide effective clinical and patient outcomes for older patients having co-morbidities Context Few studies have evaluated whether health care assistants can improve care for depressed patients . Contribution Patients who were r and omly assigned to receive telephone case management by health care assistants reported slightly greater improvements in depression symptoms , better adherence to antidepressant therapies , and more favorable assessment s of the quality of their care than did patients r and omly assigned to receive usual care . Implication Telephone case management facilitated by health care assistants may be a feasible mechanism for small primary care practice s to improve care of their patients with depression . The Editors Depression causes a substantial disease burden ( 1 ) and is responsible for annual health care costs of about $ 83.1 billion in the United States ( 2 , 3 ) . Most patients with depression are treated in primary care ( 46 ) . Collaborative care can improve depression outcomes by providing decision support and clinical information for family physicians , as well as self-management support and follow-up for patients . However , evidence regarding collaborative depression care stems mostly from academic or managed care setting s in the United States ( 711 ) . In these trials , family physicians generally relied on mental health case managers and decision support from mental health specialists ( 12 ) . Case management is a patient-centered element of collaborative care that may be effective in primary care ( 13 ) . It comprises systematic tracking of patients , support for continuing the treatment , and taking action in the case of nonadherence or lack of improvement ( 14 ) . Collaborative depression care has generally yielded positive results in diverse primary care setting s ( 7 ) . The IMPACT ( Improving MoodPromoting Access to Collaborative Treatment ) trial found that care managers who were supervised by psychiatrists and who provided education and support for medication adherence reduced depression symptoms in older patients ( 15 ) . Dietrich and colleagues ( 16 ) found that telephone support , provided by a trained , central ly based mental health care manager who was supervised by a psychiatrist , improved depression symptoms . Dobscha and colleagues ( 17 ) evaluated a primary care decision-support team for depression ( comprising a psychiatrist and a mental health nurse ) and found improved care processes but no differences in depression symptoms ( 17 ) , possibly because of less intensive follow-up of patients . Small , isolated primary care setting s often have limited re sources ( 18 ) . In the United States , 26 % of primary care practice s are solo practice s or 2-person partnerships , in which extensive collaborative models would be difficult to implement , and 22 % are located in rural areas with limited access to mental health specialists ( 19 ) . Health care assistants are established professionals in primary care setting s. They have less training than U.S. physician assistants or nurse practitioners , who provide first-contact care , and need not be college graduates ( 20 ) . In Germany , health care assistants have 3 years of on-the-job training . They are mainly responsible for administrative tasks in general practice but provide basic clinical procedures ( 21 ) . Health care assistants are a potentially important re source for enhancing patient care in primary care setting s ( 20 ) . Our aim was to evaluate whether case management by a practice -based health care assistant can reduce depression symptoms and improve the process of care for patients with major depression in small primary care practice s. Methods We design ed a pragmatic , cluster r and omized , controlled trial that used practice as the unit of r and omization to avoid contamination ( 22 ) . The institutional review board of Goethe University Frankfurt am Main , Frankfurt am Main , Germany , approved the study protocol on 25 April 2005 ( 23 ) . We used written consent procedures for family physicians and patients . We recruited practice s between February 2005 and May 2005 and patients between May 2005 and July 2006 . We carried out the intervention between June 2005 and August 2007 . We completed the last follow-up for study patients in September 2007 . Setting and Participants After calculating the sample size ( 24 ) , we informed all 1600 family physicians registered with the medical association of the state of Hesse , Germany ( m and atory registration ) , about the trial and invited them by mail to participate in information meetings . As the registration list presents only names and addresses , we checked inclusion criteria only for those who participated in the meetings . We stopped recruiting when 74 practice s had enrolled , even though more practice s were interested in participating . Inclusion criteria for the practice s were acceptance of all major health plans ( 90 % of patients are covered by this type of insurance ) ( 25 ) ; provision of a primary care service , according to the definition of Starfield and colleagues ( 26 ) ; and management by a family physician . Patients were screened on special date s and referred to the trial by the family physician in the primary care practice . Inclusion criteria for patients were diagnosis of major depression with indication for any antidepressive treatment , age 18 to 80 years , access to a private telephone , ability to give informed consent , and ability to communicate in German . The diagnosis of major depression was based on a score of more than 9 points and a categorical diagnosis in the Patient Health Question naire-9 ( PHQ-9 ) ( 27 ) , and was confirmed by the family physician by using the checklists in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and International Classification of Diseases , Tenth Edition . New patients were double-screened with the same procedure within 2 weeks . Exclusion criteria were confirmed pregnancy , severe alcohol or illicit drug consumption , or acute suicidal ideation assessed by the family physician . R and omization and Interventions The data safety and monitoring board stratified the practice s according to the size of the city and performed computer-based r and omization . Patient r and om assignment status was nested within the practice status . The data safety and monitoring board was responsible for allocation concealment by keeping the r and omization results in a secure data base . Because of the practice staff training required for the behavioral intervention , patients , health care assistants , family physicians , and research ers were not blinded to assignment once the trial was started . We design ed our case management intervention in accordance with the Chronic Care Model ( 28 , 29 ) , which emphasizes proactive support for the patient by the entire practice team . We trained 1 health care assistant from each practice assigned to the intervention group in 2 workshops ( an 11-hour and a 6-hour workshop ) . This interactive training included information on depression , communication skills , telephone monitoring , and behavioral activation for the patient ( 3032 ) . The health care assistants contacted their patients by telephone twice a week in the first month and than once a month for the following 11 months . They monitored depression symptoms and adherence to medication by using the Depression Monitoring List ( 33 ) . Health care assistants also encouraged patients to follow self-management activities , such as medication adherence and activation for pleasant or social activities . The assistants provided this information to the family physician in a structured report that stratified the urgency of the contact by a robot scheme . Family physicians in both the intervention and control groups received training on evidence -based depression treatment guidelines ( 34 ) . During the trial , other forms of disease or case management programs were uncommon in Germany ( 35 ) . No study practice carried out case management for any other diseases . Outcomes and Follow-up Self-rating question naires were h and ed out to the patients at baseline and at 6 and 12 months after baseline . Patients filled in the question naires at home and sent them back to the practice . We collected the question naires in the practice s and collected data from patient records ( number of family physician and specialist contacts , hospitalization , and prescribed medication ) . Research staff carried out data input and management ( 36 ) . Serious adverse events were reported to the data safety and monitoring board . Clinical Outcomes The primary outcome was depression symptoms , which we assessed by using the primary carevali date d PHQ-9 ( 37 ) . Each item is scored from 0 ( not at all ) to 3 ( nearly every day ) , for a total score that ranges from 0 to 27 ( high scores indicate more severe depression ) . We assessed response ( 50 % improvement in PHQ-9 score ) and remission status ( PHQ-9 score<5 ) as secondary outcomes . We also report data for the following secondary outcomes : quality of life , patient assessment of chronic illness care , and medication adherence . We measured health-related quality of life by using the Medical Outcomes Study Short Form 36 ( SF-36 ) ( 38 , 39 ) and the EuroQol-5D ( 40 ) . The SF-36 allows the calculation of scores for physical health and mental health ( range , 0 to 100 ; higher scores indicate better status ) . The EuroQol-5D is a generic instrument that measures health-related quality of life with a visual analogue scale ( range , 0 to 100 ; higher ratings indicate higher quality of life ) . We determined the number of physical comorbid conditions by counting the documented diagnoses from different diagnostic groups listed in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and International Classification of Diseases , Tenth Edition , excluding all psychiatric diagnoses in the patient record . We assessed severity of chronic physical diseases by using the Chronic Disease Score , on the basis of prescription data from the patient record ( 41 ) . Process-of-Care Outcomes We assessed the number of family physician and mental health specialist contacts , as well as prescriptions for AIMS This paper reports a study investigating the effectiveness of an adaptation training programme ( ATP ) to help patients with end-stage renal disease ( ESRD ) to cope with illness-related stresses and , thus , to alleviate depression and improve quality of life . BACKGROUND Patients with ESRD who receive dialysis must confront the burdens of long-term illness and numerous treatment-associated stressors . The ability of these patients to cope with and adapt to these stresses , whether related to their medical regimen or to the dem and s of daily life , has an important influence on physical and psychological well-being . METHODS The study was a r and omized controlled trial using a convenience sample of 57 eligible , fully informed and consenting patients with ESRD who were assigned to experimental ( ATP plus usual care ) or control ( usual care ) groups . Participants in the ATP took part in weekly small group sessions over an 8-week period and monthly follow-up to help them to cope with stressors . A clinical nurse specialist and an experienced psychotherapist led them in three small groups ( 8 - 10 per group ) . Participants in the usual care group received routine care . Instruments comprised the Haemodialysis Stressor Scale , Beck Depression Inventory and Medical Outcomes Study SF-36 . Data were collected at baseline and at three months following the intervention . RESULTS The major stressors for these patients were limitations on time and place related to employment , limitations on fluid intake , transport difficulties , loss of bodily function , length of dialysis treatment , and limitation of physical activities . The ATP had a beneficial effect on perceived stress ( P = 0.005 ) , depression ( P = 0.001 ) and quality of life ( P = 0.02 ) 3 months after the intervention . CONCLUSIONS This study supports the effectiveness of an ATP to decrease stress and depression levels , and to improve the quality of life of ATP patients receiving haemodialysis Background We evaluated the psychometric characteristics of the Short Form 36 ( SF-36 ) Health Survey and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale in patients with ankylosing spondylitis ( AS ) . Methods We analyzed clinical and patient-reported outcome ( PRO ) data collected during 12-week , double-blind , placebo-controlled periods of two r and omized controlled trials comparing adalimumab and placebo for the treatment of active AS . The Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , and other clinical measures were collected during the clinical trial . We evaluated internal consistency/reliability , construct validity , and responsiveness to change for the SF-36 and FACIT-Fatigue . Results The SF-36 ( Cronbach alpha , 0.74 - 0.92 ) and FACIT-Fatigue ( Cronbach alpha , 0.82 - 0.86 ) both had good internal consistency/reliability . At baseline , SF-36 and FACIT-Fatigue scores correlated significantly with Ankylosing Spondylitis Quality of Life scores ( r = -0.36 to -0.66 and r = -0.70 , respectively ; all p < 0.0001 ) . SF-36 scores varied by indicators of clinical severity , with greater impairment observed for more severe degrees of clinical activity ( all p < 0.0001 ) . FACIT-Fatigue scores correlated significantly with SF-36 scores ( r = 0.42 to 0.74 ; all p < 0.0001 ) and varied by clinical severity ( p < 0.05 to p < 0.0001 ) . Conclusions The SF-36 is a reliable , valid , and responsive measure of health-related quality of life and the FACIT-Fatigue is a brief and psychometrically sound measure of the effects of fatigue on patients with AS . These PROs may be useful in evaluating effectiveness of new treatments for AS.Trial Registration Clinical Trials.gov : NCT00085644 and BACKGROUND Heart failure and left ventricular systolic dysfunction ( LVSD ) are increasingly common disorders , with outcomes worse than many cancers . Evidence -based therapies , such as ACE inhibitors and beta-blockers , improve prognosis and symptoms , and reduce healthcare expenditure . However , despite the high prevalence and malignant prognosis , few studies have reported the impact of heart failure and LVSD on overall quality of life and , more crucially , have not research ed the elderly or those in the community . METHODS All patients attending the Echocardiographic Heart of Engl and Screening ( ECHOES ) study of the prevalence of heart failure and LVSD in the community were assessed by clinical history and examination , electrocardiogram and echocardiography , and also completed the SF36 health status question naire . Quality of life in patients found to have heart failure , LVSD , and other cardiac and medical conditions are compared with the r and omly selected general population sample . Data are generalisable to the UK . RESULTS 6162 people in the community were screened in the ECHOES study , of whom 5961 ( 97 % ) completed the SF36 . The health perceptions of 3850 people aged 45 years or older selected r and omly from the population were compared with those of 426 patients diagnosed as having definite heart failure . Those with heart failure had significant impairment of all the measured aspects of physical and mental health , in addition to declines in physical functioning . Significantly worse impairment was found in those with more severe heart failure by NYHA class : indeed , NYHA functional class was closely correlated to SF36 score . Patients with asymptomatic left ventricular dysfunction and patients rendered asymptomatic by treatment had similar scores to the r and om population sample . Those with heart failure reported more severe physical impairment of quality of life than people giving a history of chronic lung disease or arthritis , with less impact on mental health than patients reporting depression . CONCLUSIONS Patients with heart failure have statistically significant impairment of all aspects of quality of life , not simply physical functioning . The physical ( role and functioning ) health burden was significantly greater than that suffered in other serious common chronic disorders , whether cardiac or other systems . Optimising treatment to improve NYHA class appears to improve perceptions of quality of life for patients with heart failure . Given the dramatic decline in quality of life with heart failure , this end-point should be a much more important target for healthcare interventions , especially treatments such as ACE inhibitors and beta-blockers that are shown to improve quality of life AIM To evaluate the effects of a self-care promoting problem-based learning programme for people with rheumatic diseases in terms of health-related quality of life , empowerment , and self-care ability . BACKGROUND Individuals with rheumatoid arthritis express a great need for education and support in adapting to the disease , but the average qualities of studies about patient education interventions are not high . There is no evidence of long-term benefits of patient education . DESIGN R and omized controlled trial . METHODS A r and omized controlled design was selected with test at baseline , 1-week and 6-month post- interventions after completed the 1-year programme . The tests consisted of validity and reliability tested instruments . The participants were r and omly assigned in spring 2009 to either the experimental group ( n = 54 ) or the control group ( n = 148 ) . The programme was running alongside the st and ard care the participants received at a rheumatology unit . Parametric and non-parametric tests were used in the analyses . RESULTS The participants in the experimental group had statistically significant stronger empowerment after participation in the self-care promoting problem-based learning programme compared with the control group , at the 6-month post-intervention . Approximately , two-thirds of the participants in the experimental group stated that they had implemented lifestyle changes due to the programme . CONCLUSION The self-care promoting problem-based learning programme enabled people with rheumatic diseases to improve their empowerment compared with the control group . It is important to continue to develop problem-based learning in patient education to find the very best way to use this pedagogical method in rheumatology care Background Chronic ( systolic ) heart failure ( CHF ) represents a clinical syndrome with high individual and societal burden of disease . Multifaceted interventions like case management are seen as promising ways of improving patient outcomes , but lack a robust evidence base , especially for primary care . The aim of the study was to explore the effectiveness of a new model of CHF case management conducted by doctors ' assistants ( DAs , equivalent to a nursing role ) and supported by general practitioners ( GPs ) . Methods This patient-r and omised controlled trial ( phase II ) included 31 DAs and employing GPs from 29 small office-based practice s in Germany . Patients with CHF received either case management ( n = 99 ) consisting of telephone monitoring and home visits or usual care ( n = 100 ) for 12 months . We obtained clinical data , health care utilisation data , and patient-reported data on generic and disease-specific quality of life ( QoL , SF-36 and KCCQ ) , CHF self-care ( EHFScBS ) and on quality of care ( PACIC-5A ) . To compare between groups at follow-up , we performed analyses of covariance and logistic regression models . Results Baseline measurement showed high guideline adherence to evidence -based pharmacotherapy and good patient self-care : Patients received angiotensin converting enzyme inhibitors ( or angiotensin-2 receptor antagonists ) in 93.8 % and 95 % , and betablockers in 72.2 % and 84 % , and received both in combination in 68 % and 80 % of cases respectively . EHFScBS scores ( SD ) were 25.4 ( 8.4 ) and 25.0 ( 7.1 ) . KCCQ overall summary scores ( SD ) were 65.4 ( 22.6 ) and 64.7 ( 22.7 ) . We found low hospital admission and mortality rates . EHFScBS scores ( -3.6 [ -5.7;-1.6 ] ) and PACIC and 5A scores ( both 0.5 , [ 0.3;0.7/0.8 ] ) improved in favour of CM but QoL scores showed no significant group differences ( Physical/Mental SF-36 summary scores/KCCQ-os [ 95%CI ] : -0.3 [-3.0;2.5]/-0.1 [-3.4;3.1]/1.7 [ -3.0;6.4 ] ) . Conclusions In this sample , with little room for improvement regarding evidence -based pharmacotherapy and CHF self-care , case management showed no improved health outcomes or health care utilisation . However , case management significantly improved performance and key intermediate outcomes . Our study provides evidence for the feasibility of the case management model . Trial registration numberIS RCT AIMS AND OBJECTIVES To determine whether the management of type 2 diabetes mellitus in a primary care setting can be safely transferred to practice nurses . BACKGROUND Because of the increasing prevalence of type 2 diabetes mellitus and the burden of caring for individual patients , the dem and type 2 diabetes mellitus patients place on primary health care re sources has become overwhelming . DESIGN R and omised controlled trial . METHODS The patients in the intervention group were cared for by practice nurses who treated glucose levels , blood pressure and lipid profile according to a specified protocol . The control group received conventional care from a general practitioner . The primary outcome measure was the mean decrease seen in glycated haemoglobin ( HbA1c ) levels at the end of the follow-up period ( 14 months ) . RESULTS A total of 230 patients was r and omised with 206 completing the study . The between-group differences with respect to reduction in HbA1c , blood pressure and lipid profile were not significant . Blood pressure decreased significantly in both groups ; 7.4/3.2 mm Hg in the intervention group and 5.6/1.0 mm Hg in the control group . In both groups , more patients met the target values goals for lipid profile compared to baseline . In the intervention group , there was some deterioration in the health-related quality of life and an increase in diabetes-related symptoms . Patients being treated by a practice nurse were more satisfied with their treatment than those being treated by a general practitioner . CONCLUSION Practice nurses achieved results , which were comparable to those achieved by a general practitioner with respect to clinical parameters with better patient satisfaction . RELEVANCE TO CLINICAL PRACTICE This study shows that diabetes management in primary care can be safely transferred to practice nurses OBJECTIVES To evaluate an integrated telehealth intervention ( Integrated Telehealth Education and Activation of Mood ( I-TEAM ) ) to improve chronic illness ( congestive heart failure , chronic obstructive pulmonary disease ) and comorbid depression in the home healthcare setting . DESIGN R and omized controlled trial . SETTING Hospital-affiliated home healthcare setting . PARTICIPANTS Medically frail older homebound individuals ( N = 102 ) . INTERVENTION The 3-month intervention consisted of integrated telehealth chronic illness and depression care , with a telehealth nurse conducting daily telemonitoring of symptoms , body weight , and medication use ; providing eight weekly sessions of problem-solving treatment for depression ; and providing for communication with participants ' primary care physicians , who also prescribed antidepressants . Control participants were allocated to usual care with in-home nursing plus psychoeducation ( UC+P ) . MEASUREMENTS The two groups were compared at baseline and 3 and 6 months after baseline on clinical measures ( depression , health , problem-solving ) and 12 months after baseline on health utilization ( readmission , episodes of care , and emergency department ( ED ) visits ) . RESULTS Depression scores were 50 % lower in the I-TEAM group than in the UC+P group at 3 and 6 months . Those who received the I-TEAM intervention significantly improved their problem-solving skills and self-efficacy in managing their medical condition . The I-TEAM group had significantly fewer ED visits ( P = .01 ) but did not have significantly fewer days in the hospital at 12 months after baseline . CONCLUSION Integrated telehealth care for older adults with chronic illness and comorbid depression can reduce symptoms and postdischarge ED use in home health setting AIMS Quality of life ( QoL ) is often impaired in patients with atrial fibrillation ( AF ) . A novel nurse-led integrated chronic care approach demonstrated superiority compared with usual care in terms of cardiovascular hospitalization and mortality . Consequently , we hypothesized that this approach may also improve QoL and AF-related knowledge , which in turn may positively correlate with QoL. METHODS AND RESULTS In this r and omized controlled trial , 712 patients were r and omly assigned to nurse-led care vs. usual care . Nurse-led care consisted of guidelines -based , software supported care , supervised by cardiologists . Usual care was provided by cardiologists in the regular outpatient setting . Quality of life was assessed by means of the Medical Outcomes Study 36-Item Short-Form Survey ( SF-36 ) . The Hospital Anxiety and Depression Scale ( HADS ) was used to assess anxiety and depression scores . The AF knowledge scale was used to gain an insight into the patients ' AF knowledge levels . Baseline QoL scores were relatively high in both groups , with median scores ranging from 55 to 100 . Quality of life significantly improved over time in both groups with no significant differences between the two groups . Atrial fibrillation-related knowledge improved over time and was significantly higher at follow-up in the intervention group , compared with the usual care group ( 8.23 ± 2.16 vs. 7.66 ± 2.09 ; P < 0.05 ) . Quality of life was correlated with gender ( rs : -5.819 to -2.960 ) , anxiety ( rs : -0.746 to -0.277 ) , depression ( rs : -0.596 to -0.395 ) , and knowledge ( rs : 0.145 - 0.245 ) , expressed in Spearman 's rank correlation coefficient ( rs ) . CONCLUSION Quality of life including anxiety and depression improved over time , regardless of the treatment group . The AF-related knowledge level was better in the nurse-led care group at follow-up . Trial registration information : Clinical trials.gov identifier number : NCT00753259 Purpose Medical and health policy providers should be aware of the impact of adult spinal deformity ( ASD ) on health-related quality of life ( HRQL ) . The purpose of this study was to compare the relative burden of four chronic conditions with that of ASD . Methods The International Quality of Life Assessment project gathered data from 24,936 people and published the SF-36 scores of patients with self-reported arthritis , chronic lung disease , diabetes and congestive heart failure from 8 industrialized countries ( 3 continents ) Alonso et al. ( Qual Life Res Int J Qual Life Asp Treat Care Rehabil 13:283–298 , 2004 ) . We compared these with the SF-36 baseline data of consecutive patients with ASD enrolled in a prospect i ve multicentre international data base with the following inclusion criteria : age > 18 years and scoliosis > 20 ° , sagittal vertical axis > 5 cm , pelvic tilt > 25 ° or thoracic kyphosis > 60 ° . Four ASD groups were considered : all ASD patients , surgical c and i date s ( preop HRQL scores ) , and non-surgical c and i date s with and without previous surgery . Adjusted estimates of the impact of chronic disease were calculated using separate multivariate linear regression models . Individuals without chronic conditions were used as the reference group . Coefficients for each chronic condition and ASD represent the difference compared with this healthy group . Results 766 patients ( mean age 45.8 years ) met the inclusion criteria for ASD . The scores on all SF-36 domains were lower in ASD patients than in any other chronic condition . Differences between ASD and the other chronic conditions were always greater than the reported minimal clinical ly important differences . When compared with individuals reporting no medical conditions , SF-36 scores from the population with self-reported chronic conditions ranged from −2.5 to −14.1 . Comparable scores for patients with ASD ranged from −10.9 to −45.0 . Physical function , role physical and pain domains showed the worst scores . Surgical c and i date s with ASD displayed the worst HRQL scores ( −17.4 to −45.0 ) and patients previously operated the best ( −10.9 to −33.3 ) ; however , even the latter remained worse than any scores for the other self-reported chronic conditions . Conclusions The global burden of ASD was huge compared with other self-reported chronic conditions in the general population of eight industrialized countries . The impact of ASD on HRQL warrants the same research and health policy attention as other important chronic diseases Purpose : This r and omized controlled trial examined the effect harmonica playing has on various clinical , psychosocial , and functional outcomes among chronic obstructive pulmonary disease ( COPD ) patients in pulmonary rehabilitation ( PR ) . Method : Twenty‐eight participants ( Age 69.9 ± 1.8 ; FEV1 Predicted 41.9 ± 2.0 % ) were recruited from an outpatient PR program . Participants were r and omly assigned to one of two groups , traditional PR ( C ; n = 16 ) or traditional PR plus harmonica playing ( HT ; n = 9 ) . The HT group was provided a harmonica and one‐on‐one instruction by PR staff . Patients were given practice exercises to perform for at least 5 minutes , but not exceeding 20 minutes twice/day , 5 days/week . Results : No significant differences were found between groups . The combined sample improved significantly in their perception of shortness of breath , quality of life , and distance walked in 6 minutes . Conclusion : Harmonica playing does not significantly affect the clinical , psychosocial , or functional status of COPD patients enrolled in PR Background — Trials investigating efficacy of disease management programs ( DMP ) in heart failure reported contradictory results . Features rendering specific interventions successful are often ill defined . We evaluated the mode of action and effects of a nurse-coordinated DMP ( HeartNetCare-HF , HNC ) . Methods and Results — Patients hospitalized for systolic heart failure were r and omly assigned to HNC or usual care ( UC ) . Besides telephone-based monitoring and education , HNC addressed individual problems raised by patients , pursued networking of health care providers and provided training for caregivers . End points were time to death or rehospitalization ( combined primary ) , heart failure symptoms , and quality of life ( SF-36 ) . Of 1007 consecutive patients , 715 were r and omly assigned ( HNC : n=352 ; UC : n=363 ; age , 69±12 years ; 29 % female ; 40 % New York Heart Association class III-IV ) . Within 180 days , 130 HNC and 137 UC patients reached the primary end point ( hazard ratio , 1.02 ; 95 % confidence interval , 0.81–1.30 ; P=0.89 ) , since more HNC patients were readmitted . Overall , 32 HNC and 52 UC patients died ( 1 UC patient and 4 HNC patients after dropout ) ; thus , uncensored hazard ratio was 0.62 ( 0.40–0.96 ; P=0.03 ) . HNC patients improved more regarding New York Heart Association class ( P=0.05 ) , physical functioning ( P=0.03 ) , and physical health component ( P=0.03 ) . Except for HNC , health care utilization was comparable between groups . However , HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure – related issues . Conclusions — The primary end point of this study was neutral . However , mortality risk and surrogates of well-being improved significantly . Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N23325295 BACKGROUND AND OBJECTIVE Telemedicine , care provided by electronic communication , may serve as an alternative or extension to traditional outpatient visits . This pilot study determined the effects of telemedicine on health-care utilization and health status of chronic obstructive pulmonary disease ( COPD ) patients . METHODS One hundred and one patients were r and omized , 52 patients received telemedicine care and 49 had traditional outpatient visits . The primary outcome was COPD -specific health status , measured with the Clinical COPD Question naire ( CCQ ) . Secondary outcomes included St. George 's Respiratory Question naire ( SGRQ ) and the Short Form-36 ( SF-36 ) and re source use in primary and secondary care . RESULTS The mean age of the participants was 68 ± 9 years and the mean per cent of predicted forced expiratory volume in 1 s was 40.4 ± 12.5 . The CCQ total score deteriorated by 0.14 ± 0.13 in the telemedicine group , and improved by -0.03 ± 0.14 in the control group ( difference 0.17 ± 0.19 , 95 % confidence interval ( CI ) : -0.21 - 0.55 , P = 0.38 ) . The CCQ symptom domain showed a significant and clinical ly relevant difference in favour of the control group , 0.52 ± 0.24 ( 95 % CI : 0.04 - 0.10 , P = 0.03 ) . Similar results were found for the SGRQ , whereas results for SF-36 were inconsistent . Patients in the control group had significantly fewer visits to the pulmonologist in comparison to patients in the telemedicine group ( P = 0.05 ) . The same trend , although not significant , was found for exacerbations after 6 months . CONCLUSIONS This telemedicine model of initiated phone calls by a health-care provider had a negative effect on health status and re source use in primary and secondary care , in comparison with usual care and therefore can not be recommended in COPD patients in its current form OBJECTIVES The authors test the reliability and validity of the Medical Outcomes Study Short Form 36-Item Health Survey ( SF-36 ) as a written , self-administered survey in out patients with chronic schizophrenia . METHODS Thirty-six schizophrenic out patients completed a written and oral form of the SF-36 . A psychiatrist rated the patients using the Brief Psychiatric Rating Scale to determine severity of psychopathology . Cognitive functioning and academic achievement were also assessed . Internal consistency , test-retest reliability , concurrent and discriminative validity of the oral and written versions were determined . RESULTS The SF-36 in both forms was shown to have good internal consistency , stability , and concurrent validity . The mental health SF-36 subscales had poor discriminant validity , compared with the physical functioning scale that demonstrated good discriminant validity . CONCLUSIONS The validity of using the written form of the SF-36 on a sample of patients with chronic mental illness was demonstrated . The SF-36 appears to be an appropriate outcome measure for changes in physical and role functioning in consumers of outpatient mental health programs OBJECTIVES To analyse the cost consequences of a nurse follow-up intervention for chronic non-malignant pain patients discharged from multidisciplinary pain treatment . METHODS The cost consequence analysis was based on a prospect i ve , r and omised controlled trial where 102 consecutive patients were r and omised to either an intervention group ( n=52 ) or a control group ( n=50 ) . During the 2-year intervention period , nurses visited patients every 4th month ( 7 times in total ) . Changes in health status were measured by the 8 SF-36 sub-scales . Intervention costs were based on prospect i ve registration s of nurses ' time use . Data on health care cost and re source use were collected retrospectively from administrative registers . RESULTS No statistically significant differences in health status were observed between the two groups after the 2-year intervention period . The cost of the nurse intervention programme itself was 35,000 euro ( 2004-prices ) . The average cost per patient was estimated at 668 euro per patient . During the observation period the average patient in the intervention group used other health care re sources worth 4004 euro , while the average patient in the control group used 7464 euro . This difference ( 3460 euro , 46 % ) was not statistically significant . CONCLUSION The nurse intervention did not significantly influence patients ' health status . Patients in the intervention group tended to use fewer health care re sources than those in the control group and the cost of the intervention was more than balanced out by savings in other health care re sources Objective To assess the efficacy of brief fatigue self-management ( FSM ) for medically unexplained chronic fatigue ( UCF ) and chronic fatigue syndrome ( CFS ) in primary care . Methods A r and omized controlled design was used wherein 111 patients with UCF or CFS were r and omly assigned to two sessions of FSM , two sessions of symptom monitoring support ( attention control ; AC ) , or a usual care control condition ( UC ) . Participants were assessed at baseline and at 3 and 12 months after treatment . The primary outcome , the Fatigue Severity Scale , measured fatigue impact on functioning . Analysis was by intention to treat ( multiple imputation ) and also by per protocol . Results A group × time interaction across the 15-month trial showed significantly greater reductions in fatigue impact in the FSM group in comparison with the AC group ( p < .023 ) and the UC group ( p < .013 ) . Medium effect sizes for reduced fatigue impact in the FSM group were found in comparison with the AC group ( d = 0.46 ) and the UC group ( d = 0.40 ) . The per- protocol analysis revealed large effect sizes for the same comparisons . Clinical ly significant decreases in fatigue impact were found for 53 % of participants in the FSM condition , 14 % in the AC condition , and 17 % in the UC condition . Dropout rates at the 12-month follow-up were high ( 42%–53 % ) , perhaps attributable to the burden of monthly telephone calls to assess health care use . Conclusion A brief self-management intervention for patients with UCF or CFS seemed to be clinical ly effective for reducing the impact of fatigue on functioning . Trial Registration clinical trials.gov Identifier : NCT00997451 BACKGROUND Cognitive behaviour therapy ( CBT ) for chronic fatigue syndrome ( CFS ) is an effective but intensive treatment , requiring trained therapists . A minimal intervention based on CBT for CFS , guided self-instruction , was shown to be an effective treatment when delivered in a tertiary treatment centre . Implementing this intervention in a community-based mental health centre ( MHC ) will increase the treatment capacity for CFS patients . This study evaluated the effectiveness of guided self-instruction for CFS implemented in an MHC , delivered by nurses . METHOD One hundred and twenty-three patients were r and omly assigned to either guided self-instruction ( n=62 ) or a waiting list ( n=61 ) . R and omization was computer generated , with allocation by numbered sealed envelopes . Group allocation was open to all those involved . Patients fulfilled US Centers for Disease Control and Prevention ( CDC ) criteria for CFS . Primary outcome variables were fatigue severity and physical and social functioning , measured with the Checklist Individual Strength ( CIS ) and the Medical Outcomes Survey Short Form-36 ( SF-36 ) respectively . RESULTS After 6 months , patients who followed guided self-instruction reported a significantly larger decrease in fatigue compared to the waiting list [ mean difference -8.1 , 95 % confidence interval ( CI ) -3.8 to -12.4 , controlled effect size 0.70 ] . There was no significant difference in physical and social functioning . However , post-hoc analyses showed a significant decrease in fatigue and physical disabilities following the intervention in a subgroup of patients with physical disabilities at baseline ( SF-36 physical functioning ⩽70 ) . CONCLUSIONS Implementation of guided self-instruction in a community-based MHC was partially successful . The minimal intervention can be effectively implemented for CFS patients with physical impairments 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 STUDY OBJECTIVES Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines , few patients have access to rehabilitation services . The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education , efforts to improve patient self-management skills , and enhanced follow-up . DESIGN We conducted a 6-month , r and omized , controlled trial . SETTING Primary care clinics associated with an urban academic health system . PATIENTS Patients were > or = 45 years of age with a physician diagnosis of COPD , and had a > or = 20-pack-year smoking history , had experienced at least one respiratory symptom during the past 12 months , and had airflow obstruction ( ie , FEV1/FVC ratio , < 70 % ; FEV1 , < 80 % ) . INTERVENTIONS Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines , and two of the four nurses received additional training in collaborative management . Patients were r and omly assigned to usual care ( UC ) , nurse-assisted medical management ( MM ) , or nurse-assisted collaborative management ( CM ) . MEASUREMENTS The main outcome measures were of generic ( Medical Outcome Study 36-item short form [ SF-36 ] , illness intrusiveness ) and disease-specific ( St. George 's respiratory question naire [ SGRQ ] ) quality of life and self-reported health-care utilization . RESULTS Overall , 151 patients ( UC group , 51 patients ; MM group , 49 patients ; and CM group , 51 patients ) completed the study , their average age was 69 years , and 56.9 % were women . The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 ( 95 % confidence interval [ CI ] , -7.9 to 11.2 ) , and for the CM group vs the UC group the average change was 2.5 ( 95 % CI , -7.0 to 12.3 ) . The corresponding changes in SGRQ total domain were -2.9 ( 95 % CI , -9.8 to 4.1 ) and -2.6 ( 95 % CI , -9.5 to 4.3 ) . There was no change in the number of self-reported emergency department visits or hospitalizations , but the utilization of these services was infrequent . CONCLUSION The findings of our investigation and those from the published literature suggest that interventions to enhance patient education , self-management skills , and follow-up among patients with COPD do not result in clinical ly meaningful improvements in health status or self-reported health-care utilization . Moreover , future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities , exercise , and social support Background Nowadays , heart failure ( HF ) related morbidity and mortality rate is increasing globally . Younger population s happen to be more affected by HF in sub- Saharan African than the western countries . Even though medications , low sodium diet , regular exercise , and weight monitoring are essential to control heart failure symptoms and its exacerbation , poor adherence to these self-care recommendations is contributing to an increased in hospitalization , morbidity , and mortality . Therefore , this study aim ed to assess heart failure patients ’ adherence to self-care recommendations and its associated factors . Methods A hospital-based cross-sectional study was conducted on 310 adult heart failure patients attending Gondar University referral hospital from February to May 2017 . The participants were selected by systematic r and om sampling technique . Data were collected through face to face interview and from the patients ’ medical records . The data were analyzed using SPSS version 20 . A binary logistic regression model was used to check the effect of different factors on the patients ’ adherence level . Results Of 310 study participants only 22.3 % ( 95 % CI , 17.4%-26.8 % ) of heart failure patients reported good adherence to their self-care recommendations . Adherence to self-care recommendation was positively associated with being male in gender ( AOR = 2.34 , 95 % CI : 1.18–4.62 ) , good level of heart failure knowledge ( AOR = 2.49 , 95 % CI : 1.276–4.856 ) and free from chronic comorbid diseases ( AOR = 2.57 , 95 % CI : 1.28–5.14 ) . Conclusion Overall , heart failure patients ’ adherence to self-care recommendations is poor and selective . Being male in gender , had no chronic comorbidity , and a good level of heart failure knowledge were positively associated with adherence to self-care recommendations . It is therefore strategic to plan improving heart failure patients ’ knowledge about heart failure signs , symptoms and its management approaches , to improve the patients ’ adherence level BACKGROUND Patients with chronic heart failure have a reduced quality of life due in part to their limited range of physical activity and independence . OBJECTIVES The paper examines whether a physical activity ' lifestyle ' intervention , based on motivational interviewing , will improve quality of life at five months from baseline , compared with conventional treatment . METHODS Sixty older patients with chronic heart failure were r and omly assigned to either a ' st and ard care ' , ' motivational interviewing ' or ' both ' treatment groups for five months in 2002 . The primary outcome measures were the Medical Outcomes Short Form-36 Health Survey , the disease-specific Minnesota Living with Heart Failure question naire and the Motivation Readiness for Physical Activity scale . RESULTS There were non-significant differences between the groups at baseline for age , coronary risk factors , severity of chronic heart failure , ejection fraction , specific laboratory tests , length of hospitalisation , medication and social support . Following treatment there was a significant increase ( p<0.05 ) for three of the dimensions of the health survey in the ' motivational interviewing ' group . All groups improved their scores ( p<0.05 ) on the heart failure question naire . Over the five month period there was a general trend towards improvements in self-efficacy and motivation scores . CONCLUSIONS This study has demonstrated that a ' motivational interviewing ' intervention , incorporating behaviour change principles to promote physical activity , is effective in increasing selected aspects of a general quality of life question naire and a disease-specific quality of life question naire . Thus a ' motivational interviewing ' approach is a viable option compared with traditional exercise programming . It is important to test these motivational interviewing interventions more widely , especially to match individuals to treatments |
11,241 | 31,322,289 | Low- quality evidence suggests there may be little difference in pain and function at 12 months follow-up in people who have arthroscopic partial meniscectomy and those who have physical therapy .
Due to very low quality evidence , we are uncertain if surgery is associated with an increased risk of serious adverse events , incidence of total knee replacement or withdrawal rates .
Similarly , low- quality evidence from a few small trials indicates there may not be any benefit of arthroscopic surgery over other non-surgical treatments including saline irrigation and hyaluronic acid injection , or one type of surgery over another .
We are uncertain of the risk of adverse events or of progressing to total knee replacement due to very small event rates . | BACKGROUND Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss , bony erosion , and deformity .
Many studies do not stratify their results based on the severity of the disease at baseline or recruitment .
OBJECTIVES To assess the benefits and harms of surgical intervention for the management of symptomatic mild to moderate knee osteoarthritis defined as knee pain and radiographic evidence of non-end stage osteoarthritis ( Kellgren-Lawrence grade 1 , 2 , 3 or equivalent on MRI/arthroscopy ) .
Outcomes of interest included pain , function , radiographic progression , quality of life , short-term serious adverse events , re-operation rates and withdrawals due to adverse events . | Purpose To evaluate granulocyte colony-stimulating factor ( G-CSF ) efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy for genu varum . Methods A phase II trial was conducted for evaluating the preoperative administration of G-CSF given at 10 μg/kg/day for 3 consecutive days with an additional half-dose 4 h before the opening-wedge high tibial valgus osteotomy . Overall , 12 patients ( Group A ) received G-CSF treatment , and the subsequent 12 patients ( Group B ) underwent surgery without G-CSF . The osteotomy gap was filled by a bone graft substitute . Bone marrow cell ( BMC ) mobilization was monitored by CD34+ve cell and clonogenic progenitor cell analysis . All patients underwent a clinical ( Lysholm Knee Scale and SF-36 ) and radiographic evaluation preoperatively , as well as at given intervals postsurgery . Results All patients completed the treatment program without major side effects ; G-CSF was well tolerated . BMC mobilization occurred in all Group A patients , with median peak values of circulating CD34+ve cells of 110/μL ( range 29–256 ) . Circulating clonogenic progenitors paralleled CD34+ve cell levels . A significant improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared to Group B. At the radiographic evaluation , there was a significant increase in osseointegration at the bone-graft junction in Group A at 1 , 2 , 3 and 6 months postsurgery compared to Group B. The computerized tomography scan of the grafted area at 2 months postsurgery showed no significant difference in the quality of the newly formed bone between the two Groups . Conclusions Although the limited number of patients does not allow firm conclusions , the study suggests that G-CSF can be safely administered preoperatively in subjects undergoing opening-wedge high tibial valgus osteotomy ; in addition , the clinical , radiographic and CT monitoring indicate that G-CSF and /or mobilized BMC s may hasten bone graft substitute osseointegration . Level of evidence Purpose Early knee OA is a significant problem that can be disabling . The purpose of this study was to underst and the symptomatic profile of patients with early knee OA when compared to those with end-stage knee OA . Methods A cross-sectional case control study design was used to compare those with early structural change to those with advanced structural change . In total , 100 consecutive patients with early radiographic knee OA presenting to the knee service outpatient clinic from December 2010 to August 2011 were prospect ively identified on the basis of their radiographic changes . All met the symptomatic and radiological diagnostic criteria of early knee OA as defined by Luyten et al. They were compared with 200 knees with full thickness anteromedial knee OA and 200 knees with full thickness tricompartmental knee OA for their demographic , pain and functional profile . Results Patients with early knee OA were younger than those with full thickness disease . However , 78 % of individual patients with early radiographic OA had pain and function scores equal to individual patients presenting for UKA , whilst 74 % of individual patients with early radiographic OA had pain and function scores that are equal to or worse than individual patients presenting for TKA . Conclusions Patients with early radiographic knee OA demonstrate considerable overlap in the severity of their symptoms with those demonstrating end-stage structural changes within the knee . Patients with early structural changes of arthritis should not be assumed by clinicians to have mild disease . In many cases , their symptoms are as bad as those with end-stage structural changes . This work will help clinicians to identify and categorise those with early arthritis and thereby assist in guiding appropriate treatments In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life Purpose We compared the effectiveness of mechanical debridement ( MD ) and bipolar radiofrequency chondroplasty ( RF ) with regard to clinical outcome , rate of revision , and progression of knee osteoarthritis . Methods Sixty patients with MRI-detected grade III cartilage lesions on the medial femoral condyle were considered for the study . For MD ( group 1 ; n = 30 ) , each lesion was debrided using a mechanical shaver . For RF ( group 2 ; n = 30 ) , each lesion was smoothed using a temperature-controlled RF probe set at 50 ° C . Results The 10-year follow-up was available for 47 patients ( 78.3 % ) . Sixty per cent of group 1 ( n = 18 ) underwent revision during the follow-up period . In contrast , the revision rate in group 2 was 23.3 % ( n = 7 ; p = 0.061 ) . The mean survival was 94.1 months ( 95 % CI 77.1–111.3 ) and 62.5 months ( 95 % CI 45.9–79.2 ) for group 2 and group 1 , respectively . Patients who did not require revision ( group 1 , n = 9 ; group 2 , n = 13 ) were assessed before surgery and 1 , 4 , and 10 years after surgery using the knee injury and osteoarthritis outcome score ( KOOS ) . At follow-up , the KOOS was higher for group 2 than group 1 . At the time of surgery , no patient showed any radiological signs of osteoarthritis . The width of the medial joint was 5.4 mm ( 95 % CI 4.3–6.5 ) and 5.6 mm ( 95 % CI 4.9–6.3 ) in the MD and RF groups , respectively ( n.s . ) . During the follow-up period , the joint space width narrowed continuously in both groups ( p < 0.001 ) , but more rapidly in the group 1 ( n.s ) . Conclusion Compared to conventional MD , 50 ° RF treatment appears to be a superior method based on short- and medium-term clinical outcomes and the progression of knee osteoarthritis . Clear predictors for the indications of different cartilage treatments and more r and omized clinical trials are needed . Level of evidence Objective Compare arthroscopic partial meniscectomy to a true sham intervention . Methods Sham-controlled superiority trial performed in three county hospitals in Denmark comparing arthroscopic partial meniscectomy to skin incisions only in patients aged 35–55 years with persistent knee pain and an MRI-confirmed medial meniscus lesion . A computer-generated table of r and om numbers generated two comparison groups . Participants and outcome assessors were blinded to group allocation . Exclusions were locking knees , high-energy trauma or severe osteoarthritis . Outcomes were collected at baseline , 3 and 24 months . We hypothesised no difference between groups . The primary outcome was the between-group difference in change from baseline to 2 years in the mean score across all five normalised Knee injury and Osteoarthritis Outcome Score ( KOOS ) subscales ( KOOS5 ) . Results Forty-four patients ( of the estimated 72 ) underwent r and omisation ; 22 in each group . Sixteen participants ( 36 % ) were non-blinded and eight participants ( 36 % ) from the sham group crossed over to the surgery group prior to the 2-year follow-up . At 2 years , both groups reported clinical ly relevant improvements ( surgery 21.8 , skin incisions only 13.6 ) , the mean difference between groups was 8.2 in favour of surgery , which is slightly less than the cut-off of 10 prespecified to represent a clinical ly relevant difference ; judged by the 95 % CI ( −3.4 to 19.8 ) , a possibility of clinical ly relevant difference could not be excluded . In total , nine participants experienced 11 adverse events ; six in the surgery group and three in the skin-incisions-only group . Conclusion We found greater improvement from arthroscopic partial meniscectomy compared with skin incisions only at 2 years , with the statistical uncertainty of the between-group difference including what could be considered clinical ly relevant . Because of the study being underpowered , nearly half in the sham group being non-blinded and one-third crossing over to surgery , the results can not be generalised to the greater patient population . Trial registration number NCT01264991 Background : The optimal treatment for middle-aged patients with knee pain and meniscal lesions has been extensively debated . Most previous studies have revealed only short-term beneficial results of knee arthroscopic surgery . The authors have previously shown a positive benefit of knee arthroscopic surgery and an exercise program after 1 year when compared with an exercise program alone . Purpose : To evaluate if knee arthroscopic surgery combined with an exercise program provided an additional long-term benefit after 3 years compared with an exercise program alone in middle-aged patients with meniscal symptoms . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Of 179 eligible patients , aged 45 to 64 years , 150 were r and omized to ( 1 ) a 3-month exercise program ( nonsurgery group ) or ( 2 ) the same as group 1 plus knee arthroscopic surgery within 4 weeks ( surgery group ) . The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) subscore of pain between baseline and the 3-year follow-up . Results from the 1-year follow-up have been published previously . Results : Both treatment groups improved significantly in the KOOS pain subscore at 3 years ’ follow-up in the intention-to-treat and as-treated analyses ( P < .001 ) . The between-group difference for the change in the KOOS pain subscore between baseline and the 3-year follow-up was no longer statistically significant , neither in the intention-to-treat analysis ( 7.6 points ; 95 % CI , –0.6 to 15.9 ; P = .068 ) nor in the as-treated analysis ( 5.3 points ; 95 % CI , –3.1 to 13.8 ; P = .216 ) . The factorial analysis of the effect of the intervention and age , onset of pain , and mechanical symptoms indicated that older patients improved more , regardless of treatment , and surgery may be more beneficial for patients without mechanical symptoms ( as-treated analysis ) . The effect of the predictive factors on the KOOS pain subscore was uncertain because of the small sample size in the subgroup analyses . Conclusion : The benefit of knee arthroscopic surgery , seen at 1 year in middle-aged patients with meniscal symptoms , was diminished at 3 years and was no longer statistically significant . Clinical Relevance : Knee arthroscopic surgery may be beneficial for middle-aged patients with meniscal symptoms in addition to an exercise program . Older age and absence of mechanical symptoms should not be contraindications to surgery . Registration : NCT01288768 ( Clinical Trials.gov identifier BACKGROUND Few studies have examined whether chondral lesions encountered in patients undergoing meniscectomy should be surgically treated . The primary aim of the ChAMP ( Chondral Lesions And Meniscus Procedures ) Trial is to determine whether there is a difference in knee pain between patients undergoing debridement versus observation of chondral lesions encountered during arthroscopic meniscectomy . This paper describes the rationale and study design for the ChAMP Trial . METHODS / DESIGN The ChAMP Trial is a r and omized controlled trial of patients aged 30 and older undergoing partial meniscectomy and r and omly allocated to debridement ( CL-Deb , N=98 ) or observation ( CL-Obs , N=92 ) of chondral lesions identified during surgery and deemed to be significant ( Outerbridge Grade II-IV ) . Patients and data collectors were unaware of treatment allocation until completion of the study . Patients with surgically insignificant ( Outerbridge Grade I ) chondral lesions or no chondral lesions were included as a third non-r and omized comparison group ( NoCL , N=76 ) . The primary outcome is the difference in knee pain assessed by WOMAC ( Western Ontario and McMaster Universities Arthritis Index ) between the CL-Deb and CL-Obs groups at 1-year after surgery . Secondary outcomes include 1-year differences in additional measures of knee pain , function , symptoms , activity , and quality of life assessed by the WOMAC , KOOS ( Knee Injury and Osteoarthritis Outcome Score ) , visual analog pain scale , and physical exam ; as well as general health assessed with the SF-36 ( Short-form Health Survey ) . Increased intraoperative costs associated with the addition of chondral debridement will also be assessed . DISCUSSION This study will add to the scant literature regarding management of chondral lesions in patients undergoing meniscectomy and might provide treatment guidance for clinicians and their patients Purpose Autologous Matrix-Induced Chondrogenesis ( AMIC ® ) utilizing a type I/III collagen membrane was compared with microfracture ( MFx ) alone in focal cartilage lesions of the knee at one , two and five years . Methods Forty-seven patients ( aged 37 ± 10 years , mean defect size 3.6 ± 1.6 cm2 ) were r and omized and treated either with MFx , with sutured or glued AMIC ® in a prospect i ve multicentre clinical trial . Results After improvement for the first two years in all subgroups , a progressive and significant score degradation was observed in the MFx group , while all functional parameters remained stable for least five years in the AMIC ® groups . At two and five years , MRI defect filling was more complete in the AMIC ® groups . No treatment-related adverse events were reported . Conclusions AMIC ® is an effective cartilage repair procedure in the knee result ing in stable clinical results significantly better than the MFx group at five years Aims The aim of this prospect i ve r and omised study was to compare the time course of clinical improvement during the first two years following a closing or opening wedge high tibial osteotomy ( HTO ) . It was hypothesised that there would be no differences in clinical outcome between the two techniques . Patients and Methods Between 2007 and 2013 , 70 consecutive patients were r and omly allocated to undergo either a closing or opening wedge HTO . All patients had medial compartment osteoarthritis ( OA ) , and were aged between 30 years and 60 years . They were evaluated by independent investigators pre‐operatively and at three and six months , and one and two years postoperatively using the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , the Oxford Knee Score ( OKS ) , the Lysholm score , the Tegner activity score , the University of California , Los Angeles ( UCLA ) activity scale and range of movement ( ROM ) . Results There were no significant differences at any time between the two techniques for any clinical outcome score ( p > 0.05 ) . The mean scores for all the systems , except UCLA and Tegner , significantly improved until six months post‐operatively ( p < 0.001 ) . For some scores , the improvement continued until one and two years . Conclusion This prospect i ve r and omised study suggests that there are no differences in the time course of the clinical improvement between the closing and opening wedge techniques for HTO during the first two post‐operative years . Patients can expect continued improvement in physical function for between six months and one year after HTO regardless of the technique used Summary Twenty patients with persistent symptoms due to osteoarthritis of the knee were r and omly allocated to a saline washout or control group . Both groups showed improvement . Knee washout conferred no more benefit than intra-articular saline injection OBJECTIVE To compare the therapeutic effect of impacted high tibial osteotomy and conventional high tibial osteotomy for the treatment of flexional medial osteoarthritis of knee joint in aged patients . METHODS From July 2003 to July 2006 , 30 patients with flexional medial knee osteoarthritis were treated with impacted high tibial osteotomy or conventional high tibial osteotomy r and omly . All patients , aged from 60 to 82 years , were suffered from 7 degrees to 19 degrees knee flexion deformities and 3 to 20 years medical histories . The bone healing periods , the recover of flexion and inversion deformities , and the recover of the knee joint function were observed postoperatively . The patients were followed up at 4 , 6 , 8 , 9 , 10 , 12 and 16 weeks , and 5 , 7 , 9 and 12 months postoperatively . The bone healing periods and the recover of flexional and inversion deformities were evaluated and compared . Twelve months postoperatively , the knee joint function were assessed with the Lysholm scoring criteria , and the therapeutic effects were compared between the two groups . RESULTS There was a significant difference in the average bone healing period between the impacted high tibial osteotomy group ( 9.26 + /- 2.23 ) weeks and the conventional high tibial osteotomy group ( 11.53 + /- 3.15 ) weeks . The knee joint function were evaluated according to the Lysholm clinical rating scales . One year postoperatively , the average Lysholm score were ( 88.5 + /- 4.4 ) points in the impacted high tibial osteotomy group , and the results showed excellent in 14 cases , good in 1 . The average Lysholm score were ( 78.1 + /- 5.7 ) points in the conventional high tibial osteotomy group . The results showed 8 cases excellent , 5 good , 2 fair , accordingly . Postoperatively , the flexion deformities of the knee in the impacted high tibial osteotomy group were -1.1 degrees to 0 degrees and was corrected averagely ( 130 + /- 3.30 ) after surgery , and that in conventional high tibial osteotomy group ( 140 + /- 3.30 ) ( the same as preoperation ) . The average postoperative femorotibial angle ( FTA ) were 170.2 degrees ( ranged from 169.1 degrees to 172.3 degrees ) and was corrected 12.3 degrees to 12.5 degrees after surgery in both groups . CONCLUSION Compared with conventional high tibial osteotomy , impacted high tibial osteotomy can significantly shorten the bone healing period , improve the knee flexion , varus deformity , and the knee function Objective : Replacement of an almost completely absent medial meniscus with a collagen implant ( CMI ) , reconstruction of form and function of the medial meniscus , delay of the development of arthrosis deformans . Indications : Subtotal degenerative or traumatic loss of the medial meniscus , stable meniscal periphery , stable anterior and posterior meniscal insertions , joint with stable ligaments . Contraindications : Complete loss of the medial meniscus . Untreated knee ligament instability . Extreme varus deformity . Extensive cartilaginous damage , i.e. , levels IV and VI as described by Bauer and Jackson . Advanced unicompartmental or generalized arthrosis . Replacement of the lateral meniscus . Surgical Technique : St and ard anterior arthroscopy portals . Resection of the medial meniscus leaving a complete and stable outer rim . Revitalization of the periphery to promote healing . Measurement of defect size . Insertion and fixation of the CMI with nonresorbable suture material in inside-out technique . Postoperative Management : Postoperative knee brace with limited motion in extension/flexion of 0/0/60 ° until week 4 , 0/0/90 ° until week 6 . Coutinuous passive motion within the limits of motion from the 1st postoperative day , actively assisted physiotherapy . No weight bearing for 6 weeks , then increased weight bearing for 2 weeks until full weight bearing is achieved . Cycling can commence from 3 months postoperatively . Full sporting activity after 6 months . Results : 60 patients ( 19–68 years , average 41.6 years ) with subtotal loss of the medial meniscus and varus morphotype were treated from January 2001 to May 2004 as part of a prospect i ve , r and omized , arthroscopically controlled study . The sample consisted of 30 patients with high tibial valgus osteotomy combined with implantation of a CMI , and 30 patients with valgization correction osteotomy only . The CMI had to be removed from one patient because of a dislocation . Evaluation on the Lysholm Score , IKDC ( International Knee Documentation Committee ) , and subjective pain data revealed only slight , nonsignificant differences for 39 patients after 24 months ( CMI and correction n = 23 ; correction only n = 16 ) . The chondroprotective effect of the CMI in the long term remains to be seen OBJECTIVE To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis . DESIGN Ninety patients with knee osteoarthritis were r and omized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline ( treatment group ) or the minimal amount of irrigation ( 250 ml ) required to perform arthroscopy ( placebo group ) . The primary outcome variable was aggregate WOMAC score . RESULTS The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores , the primary outcome variable ; the mean change in aggregate WOMAC score at 12 months was 15.5 ( 95 % CI 7.7 , 23.4 ) for the full irrigation group compared to 8.9 ( 95 % CI 4.9 , 13.0 ) for the minimal irrigation group ( P=0.10 ) . Full irrigation did have a statistically significant effect on patients ' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale ( VAS ) ( the secondary outcome variables ) . Mean change in WOMAC pain scores decreased by 4.2 ( 95 % CI -0.9 , 9.4 ) for the full irrigation group compared with a mean decrease of 2.3 ( 95 % CI -0.1 , 4.7 ) in the minimal irrigation group ( P=0.04 ) . Mean VAS pain scores decreased by 1.47 ( 95 % CI -1.2 , 4.1 ) in the full irrigation group compared to a mean decrease of 0.12 ( 95 % CI 0.0 , 0.3 ) in the minimal irrigation group ( P=0.02 ) . A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessment s and aggregate WOMAC scores at 12 months ; patients with crystals had statistically greater improvements in pain . CONCLUSIONS Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA , particularly in those who have occult intraarticular crystals Background : It is still debated whether a degenerative horizontal tear of the medial meniscus should be treated with surgery . Hypothesis : The clinical outcomes of arthroscopic meniscectomy will be better than those of nonoperative treatment for a degenerative horizontal tear of the medial meniscus . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 102 patients with knee pain and a degenerative horizontal tear of the posterior horn of the medial meniscus on magnetic resonance imaging were included in this study between January 2007 and July 2009 . The study included 81 female and 21 male patients with an average age of 53.8 years ( range , 43 - 62 years ) . Fifty patients underwent arthroscopic meniscectomy ( meniscectomy group ) , and 52 patients underwent nonoperative treatment with strengthening exercises ( nonoperative group ) . Functional outcomes were compared using a visual analog scale ( VAS ) for pain , Lysholm knee score , Tegner activity scale , and patient subjective knee pain and satisfaction . Radiological evaluations were performed using the Kellgren-Lawrence classification to evaluate osteoarthritic changes . Results : In terms of clinical outcomes , meniscectomy did not provide better functional improvement than nonoperative treatment . At the final follow-up , the average VAS scores were 1.8 ( range , 1 - 5 ) in the meniscectomy group and 1.7 ( range , 1 - 4 ) in the nonoperative group ( P = .675 ) . The average Lysholm knee scores at 2-year follow-up were 83.2 ( range , 52 - 100 ) and 84.3 ( range , 58 - 100 ) in the meniscectomy and nonoperative groups , respectively ( P = .237 ) . In addition , the average Tegner activity scale and subjective satisfaction scores were not significantly different between the 2 groups . Although most patients initially had intense knee pain with mechanical symptoms , both groups reported a relief in knee pain , improved knee function , and a high level of satisfaction with treatment ( P < .05 for all values ) . Two patients in the meniscectomy group and 3 in the nonoperative group with Kellgren-Lawrence grade 1 progressed to grade 2 at the 2-year follow-up . Conclusion : There were no significant differences between arthroscopic meniscectomy and nonoperative management with strengthening exercises in terms of relief in knee pain , improved knee function , or increased satisfaction in patients after 2 years of follow-up Introduction We aim ed to identify the effects of intraoperative applied leukocyte-poor platelet-rich plasma ( LP-PRP ) during knee arthroscopy for degenerative lesions involving pain , function and quality of life . Methods We performed a r and omized controlled , double-blind trial ( RCT ) including 58 patients for arthroscopic knee surgery for cartilage or meniscal degeneration with allocation into the LP-PRP ( n = 24 ) or control group ( n = 34 ) . During arthroscopy , LP-PRP was injected intra-articular in the intervention group . At baseline , 6 weeks , 6 months and 12 months pain , function , and life quality were assessed . Results 91 % of enrolled patients were available for 12 months follow-up . Pain was significantly lower in the LP-PRP group ( VAS 0.9 . vs. 2.3 ) at 6 ( p = 0.008 ) but not at 12 months ( VAS 1.0 vs. 1.6 , p = 0.063 ) . LP-PRP application improved the Lysholm Score at 6 ( 77.5 vs. 65.6 , p = 0.033 ) and 12 months ( 83.2 vs.70.0 , p = 0.007 ) . Assessment of life quality ( SF-36 ) concerning the physical component summary was significantly higher at 6 weeks ( 33.9 vs. 25.6 , p = 0.001 ) and 6 months ( 29.9 vs. 27.1 , p = 0.027 ) in the LP-PRP group but equal at 1 year ( 31.4 vs. 30.1 , p = 0.438 ) . Conclusions Intraoperative application of LP-PRP may enhance pain reduction and gain of knee function within 6–12 months compared to arthroscopy alone . Level of evidence II , r and omized controlled clinical trial with reduced power . Clinical Trials.gov identifierNCT02189408 BACKGROUND There is great interest in the use of bone substitutes to improve bone repair . We compared the osteogenic potential of lyophilized bone chips combined with platelet gel , or with platelet gel and bone marrow stromal cells , with that of lyophilized bone chips alone in the healing of a high tibial osteotomy . METHODS A prospect i ve , r and omized , controlled study was performed , and a st and ardized clinical model was applied . Thirty-three patients undergoing high tibial osteotomy to treat genu varum were enrolled and assigned to three groups . During the osteotomy , lyophilized bone chips with platelet gel were implanted into eleven patients ( Group A ) , lyophilized bone chips with platelet gel and bone marrow stromal cells were implanted in twelve patients ( Group B ) , and lyophilized bone chips without gel were placed in ten patients as controls ( Group C ) . Six weeks after surgery , computed tomography-guided biopsies of the grafted areas were performed and the specimens were analyzed by histomorphometry . Clinical and radiographic evaluation was performed at six weeks , twelve weeks , six months , and one year after surgery . RESULTS Histomorphometry at six weeks showed significantly increased osteoblasts and osteoid areas in both Group A ( p = 0.006 and p = 0.03 , respectively ) and Group B ( p = 0.009 and p = 0.001 ) in comparison with controls , as well as increased bone apposition on the chips ( p = 0.007 and p = 0.001 , respectively ) , which was greater in Group B than in Group A ( p < 0.05 ) . Group B showed significantly higher revascularization than the controls ( p = 0.004 ) . Radiographs revealed a significantly higher rate of osseointegration in Groups A and B than in the controls at six weeks ( p < 0.005 and p < 0.0001 , respectively ) . At the final evaluation at one year , the osseointegration was still better in Groups A and B than in Group C ; however , all patients had complete clinical and functional evidence of healing . CONCLUSIONS Adding a platelet gel or a platelet gel combined with bone marrow stromal cells to lyophilized bone chips increases the osteogenetic potential of the lyophilized bone chips and may be a useful tool in the treatment of patients with massive bone loss OBJECTIVES Patients with knee osteoarthritis ( OA ) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies . The aim of this study was to compare the benefits of intra-articular corticosteroid injections ( CSIs ) and tidal irrigation ( TI ) in patients with OA of the knee . METHODS We performed a dual-centre , single blind , r and omised , parallel group trial comparing TI and CSI . Patients with knee OA were r and omised to either irrigation using a 3.2 mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1 % lidocaine . Patients were followed for 6 months . The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score ( visual analogue scale , VAS ) . RESULTS One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI . In both treatment groups , over 80 % of patients reported improvement at 2 and 4 weeks . After this time , the benefit of CSI decreased whereas that of TI was maintained : at 26 weeks the pain relief afforded by TI was significantly greater than that of CSI . At 26 weeks 29 % of the CSI group reported improvement vs 64 % of the TI group ( P<0.001 ) . Patients with a knee effusion responded better to both treatments , however , this was most apparent for CSI . Patients with less severe radiographic OA also obtained the greatest improvement from both treatments . CONCLUSION Both procedures lead to significant short-term pain relief of at least 4 weeks , however , TI displayed a significantly greater duration of benefit . Patients with effusions and milder radiographic change obtained the best response to treatment This study examined whether a non-thermal , non-invasive , pulsed electromagnetic field ( PEMF ) , known to modulate the calmodulin (CaM)-dependent nitric oxide (NO)/cyclic guanosine monophosphate ( cGMP ) signaling pathway , could reduce pain in early knee OA . This r and omized , placebo-controlled , double-blind pilot clinical study enrolled 34 patients . Patient selection required initial VAS ≥4 , 2 h of st and ing activity per day , and no recent interventions such as cortisone injections or surgery . Results showed VAS pain score decreased in the active cohort by 50 ± 11 % versus baseline starting at day 1 and persisting to day 42 ( P < 0.001 ) . There was no significant decrease in VAS versus baseline at any time point in the sham cohort ( P = 0.227 ) . The overall decrease in mean VAS score for the active cohort was nearly threefold that of the sham cohort ( P < 0.001 ) . The results suggest that non-thermal , non-invasive PEMF therapy can have a significant and rapid impact on pain from early knee OA and that larger clinical trials are warranted Medial opening-wedge has gained popularity in comparison to other techniques of high tibial osteotomy . This technique involves the creation of a gap in the tibia . Filling the gap with autologous iliac bone graft was recommended in the classic description , to prevent complications such as correction loss or delayed bone union . No previous reports have compared grafted and nongrafted osteotomies . This study hypothesized that the use of autologous bone graft in medial opening-wedge high tibial osteotomy ( MOWHTO ) less than 12.5 mm is unnecessary . A prospect i ve r and omized clinical trial was conducted . Forty-six opening-wedge high tibial osteotomies were carried out between April 2007 and December 2008 . All had fixation with a type of Puddu stainless steel plate and screws . Patients were r and omly divided by software analysis into two groups : group A had osteotomies that were filled with autologous bone graft and group B had osteotomies that were unfilled . Autologous iliac bone graft was harvested in both groups . Clinical and radiographic evaluations were performed twice monthly by blinded investigators . The rates of complications were compared between the groups . There was no difference in demographic data . Mean time to clinical bone union in group A was 12.4 weeks ( confidence interval [ CI ] 11.2 - 13.6 ) and in group B was 13.7 weeks ( CI 12.5 - 14.9 ) , but this difference was not significant ( P = 0.13 ) . Signals of correction loss occurred in one patient ( 4.35 % ) in group A , and in two patients ( 8.70 % ) in group B. All osteotomies had achieved bone union . It was concluded that time to bone union was not statistically different between the group with bone graft and the group without graft CONTEXT Knee osteoarthritis ( OA ) is a leading cause of disability in older persons . Few risk factors for disease progression or functional decline have been identified . Hip-knee-ankle alignment influences load distribution at the knee ; varus and valgus alignment increase medial and lateral load , respectively . OBJECTIVE To test the hypotheses that ( 1 ) varus alignment increases risk of medial knee OA progression during the subsequent 18 months , ( 2 ) valgus alignment increases risk of subsequent lateral knee OA progression , ( 3 ) greater severity of malalignment is associated with greater subsequent loss of joint space , and ( 4 ) greater burden of malalignment is associated with greater subsequent decline in physical function . DESIGN AND SETTING Prospect i ve longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago , Ill. PARTICIPANTS A total of 237 persons recruited from the community with primary knee OA , defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity ; 230 ( 97 % ) completed the study . MAIN OUTCOME MEASURES Progression of OA , defined as a 1- grade increase in severity of joint space narrowing on semiflexed , fluoroscopically confirmed knee radiographs ; change in narrowest joint space width ; and change in physical function between baseline and 18 months , compared by knee alignment at baseline . RESULTS Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression , adjusting for age , sex , and body mass index ( adjusted odds ratio [ OR ] , 4.09 ; 95 % confidence interval [ CI ] , 2.20 - 7.62 ) . Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression ( adjusted OR , 4.89 ; 95 % CI , 2.13 - 11.20 ) . Severity of varus correlated with greater medial joint space loss during the subsequent 18 months ( R = 0.52 ; 95 % CI , 0.40 - 0.62 in dominant knees ) , and severity of valgus correlated with greater subsequent lateral joint space loss ( R = 0.35 ; 95 % CI , 0.21 - 0.47 in dominant knees ) . Having alignment of more than 5 degrees ( in either direction ) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees , after adjusting for age , sex , body mass index , and pain . CONCLUSION This is , to our knowledge , the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression , that valgus alignment increases risk of lateral OA progression , that burden of malalignment predicts decline in physical function , and that these effects can be detected after as little as 18 months of observation BACKGROUND Arthroscopic partial meniscectomy is one of the most common orthopedic procedures , yet rigorous evidence of its efficacy is lacking . METHODS We conducted a multicenter , r and omized , double-blind , sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis . Patients were r and omly assigned to arthroscopic partial meniscectomy or sham surgery . The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool ( WOMET ) scores ( each ranging from 0 to 100 , with lower scores indicating more severe symptoms ) and in knee pain after exercise ( rated on a scale from 0 to 10 , with 0 denoting no pain ) at 12 months after the procedure . RESULTS In the intention-to-treat analysis , there were no significant between-group differences in the change from baseline to 12 months in any primary outcome . The mean changes ( improvements ) in the primary outcome measures were as follows : Lysholm score , 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group ( between-group difference , -1.6 points ; 95 % confidence interval [ CI ] , -7.2 to 4.0 ) ; WOMET score , 24.6 and 27.1 points , respectively ( between-group difference , -2.5 points ; 95 % CI , -9.2 to 4.1 ) ; and score for knee pain after exercise , 3.1 and 3.3 points , respectively ( between-group difference , -0.1 ; 95 % CI , -0.9 to 0.7 ) . There were no significant differences between groups in the number of patients who required subsequent knee surgery ( two in the partial-meniscectomy group and five in the sham-surgery group ) or serious adverse events ( one and zero , respectively ) . CONCLUSIONS In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear , the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure . ( Funded by the Sigrid Juselius Foundation and others ; Clinical Trials.gov number , NCT00549172 . ) Objectives Subtotal or total meniscectomy in the medial or lateral compartment of the knee results in a high risk of future osteoarthritis . Meniscal allograft transplantation has been performed for over thirty years with the scientifically plausible hypothesis that it functions in a similar way to a native meniscus . It is thought that a meniscal allograft transplant has a chondroprotective effect , reducing symptoms and the long-term risk of osteoarthritis . However , this hypothesis has never been tested in a high- quality study on human participants . This study aims to address this shortfall by performing a pilot r and omised controlled trial within the context of a comprehensive cohort study design . Methods Patients will be r and omised to receive either meniscal transplant or a non-operative , personalised knee therapy program . MRIs will be performed every four months for one year . The primary endpoint is the mean change in cartilage volume in the weight-bearing area of the knee at one year post intervention . Secondary outcome measures include the mean change in cartilage thickness , T2 maps , patient-reported outcome measures , health economics assessment and complications . Results This study is expected to report its findings in 2016 . Cite this article : Bone Joint Res The Unispacer knee system is a cobalt-chrome self-centring tibial hemiarthroplasty device for use in the treatment of isolated medial compartment osteoarthritis of the knee . The indications for use are similar to those for high tibial osteotomy , but insertion does not require bone cuts or component fixation , and does not compromise future knee replacement surgery . A prospect i ve study of a consecutive series of 18 patients treated with the Unispacer between June 2003 and August 2004 was carried out to determine the early clinical results of this device . The mean age of the patients was 49 years ( 40 to 57 ) . A total of eight patients ( 44 % ) required revision within two years . In two patients revision to a larger spacer was required , and in six conversion to either a unicompartmental or total knee replacement was needed . At the most recent review 12 patients ( 66.7 % ) had a Unispacer remaining in situ . The mean modified visual analogue score for these patients at a mean follow-up of 19 months ( 12 to 26 ) was 3.0 ( 0 to 11.5 ) . The mean pain level was 30 % that of the mean pre-operative level of 10 . The early clinical results using this device have been disappointing . This study demonstrates that use of the Unispacer in isolated medial compartment osteoarthritis is associated with a high rate of revision surgery and provides unpredictable relief of pain Purpose Both , knee joint distraction as a relatively new approach and valgus-producing opening-wedge high tibial osteotomy ( HTO ) , are knee-preserving treatments for knee osteoarthritis ( OA ) . The efficacy of knee joint distraction compared to HTO has not been reported . Methods Sixty-nine patients with medial knee joint OA with a varus axis deviation of < 10 ° were r and omized to either knee joint distraction ( n = 23 ) or HTO ( n = 46 ) . Question naires were assessed at baseline and 3 , 6 , and 12 months . Joint space width ( JSW ) as a surrogate measure for cartilage thickness was determined on st and ardized semi-flexed radiographs at baseline and 1-year follow-up . Results All patient-reported outcome measures ( PROMS ) improved significantly over 1 year ( at 1 year p < 0.02 ) in both groups . At 1 year , the HTO group showed slightly greater improvement in 4 of the 16 PROMS ( p < 0.05 ) . The minimum medial compartment JSW increased 0.8 ± 1.0 mm in the knee joint distraction group ( p = 0.001 ) and 0.4 ± 0.5 mm in the HTO group ( p < 0.001 ) , with minimum JSW improvement in favour of knee joint distraction ( p = 0.05 ) . The lateral compartment showed a small increase in the knee joint distraction group and a small decrease in the HTO group , leading to a significant increase in mean JSW for knee joint distraction only ( p < 0.02 ) . Conclusion Cartilaginous repair activity , as indicated by JSW , and clinical outcome improvement occurred with both , knee joint distraction and HTO . These findings suggest that knee joint distraction may be an alternative therapy for medial compartmental OA with a limited mechanical leg malalignment . Level of evidence R and omized controlled trial , Level In a r and omised clinical trial in 50 patients with symptomatic osteoarthritis of the medial compartment of the knee , the clinical results of high tibial osteotomy ( HTO ) according to the open wedge osteotomy ( OWO ) and closed wedge osteotomy ( CWO ) were compared . In both groups locked plate fixation was used . Clinical and radiological assessment s were performed preoperatively and after one year . Postoperative hip-knee-ankle ( HKA ) correction angles were monitored on st and ing leg X-rays . The effect of HTO on collateral laxity of the knee was measured with a specially design ed varus-valgus device . The WOMAC osteoarthritis index , the modified knee society score ( KS ) and visual analogue scales ( VAS ) were used to assess symptoms of osteoarthritis , function , pain and patient satisfaction . At one-year follow-up we found accurate corrections in both groups and the planned correction angles were achieved . No loss of correction was observed . Furthermore , the medial collateral laxity and the patellar height significantly decreased after OWO . Significant improvements of WOMAC and KS scores were found in both groups . All patients had significantly less pain and were very satisfied with the results . Surgery time was significantly longer in the CWO group , and complications were more frequent in this group . Both techniques led to good and comparable clinical results . The choice of whether to perform an open or a closed wedge osteotomy may be based on preoperative patellar height or concomitant collateral laxity Objective The efficacy and safety of BST-CarGel ® , a chitosan scaffold for cartilage repair was compared with microfracture alone at 1 year during a multicenter r and omized controlled trial in the knee . This report was undertaken to investigate 5-year structural and clinical outcomes . Design The international r and omized controlled trial enrolled 80 patients , aged 18 to 55 years , with grade III or IV focal lesions on the femoral condyles . Patients were r and omized to receive BST-CarGel ® treatment or microfracture alone , and followed st and ardized 12-week rehabilitation . Co- primary endpoints of repair tissue quantity and quality were evaluated by 3-dimensional MRI quantification of the degree of lesion filling ( % ) and T2 relaxation times . Secondary endpoints were clinical benefit measured with WOMAC ( Western Ontario and McMaster Universities Osteoarthritis Index ) question naires and safety . General estimating equations were used for longitudinal statistical analysis of repeated measures . Results Blinded MRI analysis demonstrated that BST-CarGel ® -treated patients showed a significantly greater treatment effect for lesion filling ( P = 0.017 ) over 5 years compared with microfracture alone . A significantly greater treatment effect for BST-CarGel ® was also found for repair tissue T2 relaxation times ( P = 0.026 ) , which were closer to native cartilage compared to the microfracture group . BST-CarGel ® and microfracture groups showed highly significant improvement at 5 years from pretreatment baseline for each WOMAC subscale ( P < 0.0001 ) , and there were no differences between the treatment groups . Safety was comparable for both groups . Conclusions BST-CarGel ® was shown to be an effective mid-term cartilage repair treatment . At 5 years , BST-CarGel ® treatment result ed in sustained and significantly superior repair tissue quantity and quality over microfracture alone . Clinical benefit following BST-CarGel ® and microfracture treatment were highly significant over baseline levels Introduction The management of intra-articular chondral defects in the knee remains a challenge . Inadequate healing in areas of weight bearing leads to impairment in load transmission and these defects predispose to later development of osteoarthritis . Surgical management of full thickness chondral defects include arthroscopic microfracture and when appropriate autologous chondrocyte implantation . This latter method however is technically challenging , and may not offer significant improvement over microfracture . Pre clinical and limited clinical trials have indicated the capacity of mesenchymal stem cells to influence chondral repair . The aim of this paper is to describe the methodology of a pilot r and omised controlled trial comparing arthroscopic microfracture alone for isolated knee chondral defects versus arthroscopic microfracture combined with postoperative autologous adipose derived mesenchymal stem cell injections . Methods and analysis A pilot single-centre r and omised controlled trial is proposed . 40 participants aged 18–50 years , with isolated femoral condyle chondral defects and awaiting planned arthroscopic microfracture will be r and omly allocated to a control group ( receiving no additional treatment ) or treatment group ( receiving postoperative adipose derived mesenchymal stem cell treatment ) . Primary outcome measures will include MRI assessment of cartilage volume and defects and the Knee Injury and Osteoarthritis Outcome Score . Secondary outcomes will include further MRI assessment of bone marrow lesions , bone area and T2 cartilage mapping , a 0–10 Numerical Pain Rating Scale , a Global Impression of Change score and a treatment satisfaction scale . Adverse events and co interventions will be recorded . Initial outcome follow-up for publication of results will be at 12 months . Further annual follow-up to assess long-term differences between the two group will occur . Ethics and dissemination This trial has received prospect i ve ethics approval through the Latrobe University Human Research Ethics Committee . Dissemination of outcome data is planned through both national and international conferences and formal publication in a peer- review ed journal . Trial registration number Australia and New Zeal and Clinical Trials Register ( ANZCTR Trial ID : ACTRN12614000812695 ) Background Focal lesions to the articular cartilage in the knee might have demolishing consequences to the knee . There exists a wide range of possible surgical procedures targeting these injuries , however no significant differences have been found between these procedures . This may support that the improvement is a result of rehabilitation , and not the surgery itself . Arthroscopic microfracture ( MF ) treatment has gained popularity , and has become the treatment of choice in patients with knee cartilage defects globally . In this study we want to increase knowledge , both clinical and economic , about arthroscopic microfracture ( AF ) compared to arthroscopic debridement ( AD ) and physical rehabilitation both in the short run , and in the long run . Methods / Design To compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of focal cartilage lesions in the knee , a long-term , double-blinded , r and omized controlled multicenter trial will be conducted . A total of 114 men and non-pregnant women with a symptomatic focal full thickness cartilage lesion in the knee less than 2 cm2 will be included in the study . The two treatment allocations will receive identical rehabilitation , which is made up of 3 phases : accommodation , rehabilitation and return to activity . Follow up is 24 months , where all will be invited to participate in late follow ups after 5 and 10 years . The Knee Injury and Osteoarthritis Outcome Score ( KOOS ) knee-related quality of life ( QoL ) subscore is the primary endpoint . Clinical parameters , question naires and radiologic modalities ( Magnetic Resonance Imaging ( MRI ) and x-ray ) will be used as secondary endpoints . Discussion This is an ongoing multicenter study with a high level of evidence to compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of isolated symptomatic full thickness cartilage lesions in the knee joint . Trial registration Clinical Trials.gov ID : NCT02637505 ( December 15 , 2015 ) Purpose The aim of this prospect i ve r and omized intervention study was to evaluate the outcome at a 2 and 5 year follow-up whether combined arthroscopic surgery followed by exercise therapy was superior to the same exercise therapy alone when treating non-traumatic , degenerative medial meniscal tears . Methods Ninety-six middle-aged patients with MRI-verified degenerative medial meniscus tear and radiographic osteoarthritis grade ≤1 ( Ahlbäck ) participated in the study . Radiographic examination was done before r and omization and after 5 years . The patients were r and omly assigned to either arthroscopic treatment followed by exercise therapy for 2 months or to the same exercise therapy alone . At the start of the study and at the follow-ups at 24 and 60 months the patients answered three question naires KOOS , Lysholm Knee Scoring Scale and Tegner Activity Scale and made pain ratings on the Visual Analogue Scale ( VAS ) . Results Both groups showed highly significant clinical improvements from baseline to the follow-ups at 24 and 60 months on all subscales of KOOS , Lysholm Knee Scoring Scale and VAS ( p < 0.0001 ) . No group differences were found at any of the testing occasions . One third of the patients that were treated with exercise therapy alone did not feel better after the treatment but were improved after arthroscopic surgery . According to radiographic findings two patients from each group had a slight progression of their osteoarthritis after 5 years . Conclusion The findings indicate that arthroscopic surgery followed by exercise therapy was not superior to the same exercise therapy alone for this type of patients . Consequently , exercise therapy can be recommended as initial treatment . However , one third of the patients from the exercise group still had disabling knee symptoms after exercise therapy but improved to the same level as the rest of the patients after arthroscopic surgery with partial meniscectomy . Level of evidence Objective : To investigate the efficacy of intermittent and continuous traction in the treatment of knee osteoarthritis . Design : A r and omized , controlled , observer-blind seven-week trial . Setting : Hospital-based outpatient practice . Subjects : Ninety-eight patients with stage 3 knee osteoarthritis according to Kellgren – Lawrence radiological rating scale . Interventions : All 98 patients were r and omly assigned to three treatment groups , for three weeks ( weekends excluded ) . The control group ( n=30 , mean age : 59.30±8.16 ) received hot pack and short wave diathermy ; the intermittent group ( n=30 , mean age : 58.20±7.78 ) received hot pack , short wave diathermy and intermittent traction ; and the continuous group ( n=30 , mean age : 57.97±9.53 ) received hot pack , short wave diathermy and continuous traction . Outcome measurements : The values of the Turkish version of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , visual analog scale , and knee passive range of motion were measured at baseline , three-week and seven-week follow-up . Results : Compared with baseline at weeks 3 and 7 , all the outcome measures , except range of motion , were significantly reduced in all groups ( all P≤0.001 ) . In terms of the change data from baseline to week 3 , both traction groups were significantly superior to the control in the WOMAC physical function scores . Considering the change data from baseline to week 7 , both traction groups were significantly superior to the control in the pain scores , physical function and total scores , while only the continuous group was significantly better than the control in the stiffness scores ( control : 1.17 ± 1.64 ; continuous : 2.38 ± 1.44 ) ( P=0.014 ) . Compared with baseline at weeks 3 and 7 , range of motion values significantly increased in both traction groups ( P<0.05 ) but not in the control ( P>0.05 ) . However , there were no significant differences among the three groups considering the change data from baseline to week 7 in range of motion values ( P=0.300 ) . Conclusions : Joint traction was found to be beneficial for the improvement of pain and physical function loss related to knee osteoarthritis This paper presents the rationale and design features of the MeTeOR Trial ( Meniscal Tear in Osteoarthritis Research ; Clinical Trials.gov NCT00597012 ) . MeTeOR is an NIH-funded seven-center prospect i ve r and omized controlled trial ( RCT ) design ed to establish the efficacy of arthroscopic partial meniscectomy combined with a st and ardized physical therapy program as compared with a st and ardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change ( OA ) . The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges . The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features , with particular attention to those that present clinical and method ologic challenges Abstract Purpose The aim of the present study was to examine changes in radiological variables in a prospect i ve r and omized study comparing opening wedge ( OW ) and closing wedge ( CW ) techniques of high tibial osteotomy ( HTO ) . Our hypothesis was that there would be no differences in joint line angles or correction accuracy between the two groups , that patellar height would increase after CW HTO and decrease after OW HTO , and that leg length and posterior tibial slope would decrease after CW HTO and increase after OW HTO . Methods Radiological data were collected from 70 patients participating in an ongoing prospect i ve r and omized clinical trial comparing OW and CW HTOs . Digital st and ing hip – knee – ankle ( HKA ) radiographs as well as lateral radiographs in 30 ° of flexion were obtained preoperatively and at 6 months for each patient . Joint line angles , HKA angle , leg length , Insall – Salvati index , Miura – Kawamura index and posterior tibial slope were measured using medical planning software . The complete preoperative radiological examinations of the first 50 patients were used in a study of intra- and inter-rater reliability of the measurements . Results The mean posterior slope was reduced by 2.5 ° in CW HTO , whereas it remained unchanged in OW HTO ( p < 0.001 ) . Mean leg length decreased 5.7 mm in CW HTO and increased 3.1 mm in OW HTO ( p < 0.001 ) . Changes in joint line angles , patellar height indexes and the correction accuracy showed no significant differences comparing the two techniques . Frontal plane reliability measurement intra- and inter-rater intraclass correlation coefficient ( ICC ) varied from 0.81 to 0.99 . Sagittal plane intra- and inter-rater ICC varied from 0.60 to 0.87 . Posterior tibial slope intra- and inter-rater ICC showed the lowest values ( 0.70 and 0.60 , respectively ) corresponding to a smallest real difference of 4.5 ° and 5.5 ° , respectively . Conclusions Posterior tibial slope and leg length changes were significantly different in CW compared to OW HTOs . We recommend that possible alterations in tibial slope and leg length are considered when the technique of HTO is to be chosen . L and mark-based medical planning software shows good reliability and can be used in preoperative planning and postoperative evaluations of HTOs . Level of evidence The aims of this study were to analyze the range of cartilage damage and patellofemoral joint ( PFJ ) degeneration in degenerative osteoarthritis ( OA ) and determine the duration for the positive effects of platelet-rich plasma ( PRP ) injection . This study included 65 patients suffering from OA that were treated with intra-articular PRP injection . The patients were prospect ively evaluated at 1 , 3 , 6 , 9 , and 12 months after the procedure using a visual analogue scale ( VAS ) score and an International Knee Documentation Committee ( IKDC ) score . Clinical improvement in the average VAS score from 7.4 before the procedure to 4.2 at 6 months post-procedure had been reported , but the symptoms tended to deteriorate to 5.0 1 year after injection . The IKDC score also showed statistical significance ( P < 0.05 ) . Patients reported relapsed pain 8.8 months after the procedure . Developing degeneration according to the Kellgren – Lawrence grade reduced the clinical effects of PRP ( P < 0.05 ) and also accelerated the time for feeling relapsed pain ( P < 0.05 ) . There was a statistically significant negative correlation between patient age and the PRP potential in the VAS score ( slope = 0.1667 ) and IKDC score ( slope = 1.3333 ) . The presence of PFJ degeneration is expected to produce a worse outcome ( P < 0.05 ) . While intra-articular PRP injection can be used for the treatment of early OA , increasing age , and developing degeneration result in a decreased potential for PRP injection therapy A prospect i ve , r and omised , controlled trial compared two different techniques of high tibial osteotomy with a lateral closing wedge or a medial opening wedge , stabilised by a Puddu plate . The clinical outcome and radiological results were examined at one year . The primary outcome measure was the achievement of an overcorrection of valgus of 4 degrees . Secondary outcome measures were the severity of pain ( visual analogue scale ) , knee function ( Hospital for Special Surgery score ) , and walking distance . Between January 2001 and April 2004 , 92 patients were r and omised to one or other of the techniques . At follow-up at one year the post-operative hip-knee-ankle angle was 3.4 degrees ( + /- 3.6 degrees SD ) valgus after a closing wedge and 1.3 degrees ( + /- 4.7 degrees SD ) of valgus after an opening wedge . The adjusted mean difference of 2.1 degrees was significant ( p = 0.02 ) . The deviation from 4 degrees of valgus alignment was 2.7 degrees ( + /- 2.4 degrees SD ) in the closing wedge and 4.0 degrees ( + /- 3.6 degrees sd ) in the opening-wedge groups . The adjusted mean difference of 1.67 degrees was also significant ( p = 0.01 ) . The severity of pain , knee score and walking ability improved in both groups , but the difference was not significant . Because of pain , the staples required removal in 11 ( 23 % ) patients in the closing-wedge group and a Puddu plate was removed in 27 ( 60 % ) patients in the opening-wedge group . This difference was significant ( p < 0.001 ) . We conclude that closing-wedge osteotomy achieves a more accurate correction with less morbidity , although both techniques had improved the function of the knee at one year after the procedure PURPOSE This r and omized study was undertaken to compare the effectiveness of simple mechanical debridement and 50 degrees C controlled bipolar chondroplasty . METHODS A total of 60 patients who had a grade III articular cartilage defect of the medial femoral condyle were included . After r and omization , 30 patients underwent simple debridement of articular cartilage defects , which was performed with a mechanical shaver ( mechanical shaver debridement [ MSD ] group ) . The remaining patients underwent thermal chondroplasty , which was performed with a temperature-controlled bipolar device with a constant thermo-application of a maximum of 50 degrees C ( radiofrequency-based chondroplasty [ RFC ] group ) . All patients underwent partial ( n = 41 ) or subtotal ( n = 19 ) meniscectomy . Follow-up was undertaken 4 years postoperatively . RESULTS No significant differences between the preoperative findings for the 2 groups were observed . One patient from the MSD group had died , and one female patient in the RFC group was lost to follow-up . A total of 18 patients had undergone revision operations for persistent knee problems : in the MSD group , there were 8 endoprostheses , 4 osteotomies , and 2 revision arthroscopies , whereas in the RFC group , there was 1 replacement , 2 osteotomies , and 1 revision arthroscopy with subtotal medial meniscectomy . The proportion of revisions was significantly higher in the MSD group ( P = .006 ) . These patients were excluded from the evaluation . The remaining 40 patients from both groups benefited from the operation . The preoperative Knee Injury and Osteoarthritis Outcome Score ( KOOS ) was 11.3 points in the MSD group and 15.5 points in the RFC group ( P = .279 ) . Patients from the MSD group had a KOOS of 53.2 points at the time of follow-up . In the RFC group the KOOS ( 71.8 points ) was significantly higher ( P < .001 ) . CONCLUSIONS Compared with classical mechanical debridement , bipolar radiofrequency currently appears to be the superior method for achieving a good midterm result . LEVEL OF EVIDENCE Level I , r and omized controlled trial Aims Meniscal allograft transplantation is undertaken to improve pain and function in patients with a symptomatic meniscal deficient knee compartment . While case series have shown improvements in patient reported outcome measures ( PROMs ) , its efficacy has not been rigorously evaluated . This study aim ed to compare PROMs in patients having meniscal transplantation with those having personalized physiotherapy at 12 months . Patients and Methods A single‐centre assessor‐blinded , comprehensive cohort study , incorporating a pilot r and omized controlled trial ( RCT ) was performed on patients with a symptomatic compartment of the knee in which a (sub)total meniscectomy had previously been performed . They were r and omized to be treated either with a meniscal allograft transplantation or personalized physiotherapy , and stratified for malalignment of the limb . They entered the preference groups if they were not willing to be r and omized . The Knee injury and Osteoarthritis Outcome Score ( KOOS ) , International Knee Documentation Committee ( IKDC ) score and Lysholm score and complications were collected at baseline and at four , eight and 12 months following the interventions . Results A total of 36 patients entered the study ; 21 were r and omized and 15 chose their treatments . Their mean age was 28 years ( range 17 to 46 ) . The outcomes were similar in the r and omized and preference groups , allowing pooling of data . At 12 months , the KOOS4 composite score ( mean difference 12 , p = 0.03 ) and KOOS subscales of pain ( mean difference 15 , p = 0.02 ) and activities of daily living ( mean difference 18 , p = 0.005 ) were significantly superior in the meniscal transplantation group . Other PROMs also favoured this group without reaching statistical significance . There were five complications in the meniscal transplantation and one in the physiotherapy groups . Conclusion This is the first study to compare meniscal allograft transplantation to non‐operative treatment . The results provide the best quality evidence to date of the symptomatic benefits of meniscal allograft transplantation in the short term , but a multicentre RCT is required to investigate this question further OBJECTIVE To evaluate the effectiveness of tidal irrigation ( TI ) in comparison with a well-matched sham irrigation ( SI ) procedure as a treatment for knee osteoarthritis ( OA ) . METHODS One hundred eighty subjects with knee OA were r and omized to receive TI or SI , with clinical followup over the ensuing 12 months . The primary outcomes of interest were change in pain and function , as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Subjects and the nurse assessor were blinded , and success of blinding was assessed . RESULTS Although the study groups were otherwise comparable , the baseline WOMAC pain and physical functioning scores were higher ( worse ) in the SI group . After adjustment for baseline , there were no differences between the effects Most studies suggested that arthroscopic microfracture is effective method at only less than 40 years of age . Thus , the authors thought that “ how can this indication regarding age be extended ? , ” and tried to find a way to use this technique effectively over 40 years of age . The aim of this study was the first to report the results regarding the PRP as an adjunct for arthroscopic microfracture in the early osteoarthritic ( OA ) knee with cartilage lesion over 40 years of age . 49 patients who underwent arthroscopic microfracture for cartilage lesion sized less than 4 cm2 with early OA , aged 40–50 years , were enrolled and r and omly divided into 2 groups : a control group with only arthroscopic microfracture ( 25 patients ) and a study group with arthroscopic microfracture and PRP ( 24 patients ) . The patients were prospect ively evaluated with VAS , IKDC score at preoperative and postoperative 1 , 6 , 12 , and 24 months . And we perform second arthroscopies in 10 patients of each group to identify the extent of cartilage restoration at 4–6 months postoperatively . There were significant improvements in clinical results between preoperative evaluation and postoperative 2 years in both groups ( p = 0.017 ) . In the postoperative 2 years , clinical results showed significantly better in the study group than in the control group ( p = 0.012 ) . In post-arthroscopic finding , hardness and elasticity degree was better in the study group . The PRP injection with arthroscopic microfracture would be improved the results in early osteoarthritic knee with cartilage lesion in 40–50 years old , and the indication of this technique could be extended to 50 years Thirty-five patients with limited extent of degenerative osteoarthritis of the femorotibial joint treated by arthroscope-guided surgery were compared after 1 - 3 years with 38 patients with a similar condition treated conservatively . In selecting a patient for arthroscope-guided surgery , the most important considerations were a normal mechanical axis , a limited extent of the degenerative process , and a femorotibial pain of sudden onset or that had been present for < 6 months . Clinical evaluation was undertaken using a modification of the Hospital for Special Surgery Knee Rating Score . The surgical procedure included partial meniscectomy , limited debridement of loose articular cartilage and removal of loose bodies . In the operated group , 26 patients ( 75 % ) showed improvement , five ( 14 % ) remained unchanged , and four ( 11 % ) were worse than before surgery . The average age of patients was 57 years . In the nonoperated group , six patients ( 16 % ) were improved , 12 ( 31 % ) unchanged , and 20 ( 53 % ) worse than before treatment . The average age of patients was 56 years . Arthroscope-guided surgery for limited degenerative osteoarthritis of the femorotibial joint with normal limb alignment or for degenerative meniscal tears has proven to be a useful technique Background : Various techniques have proven to be effective for treating articular cartilage defect ( ACD ) and osteochondral defect ( OCD ) of the knee joint , but knowledge regarding which method is best still remains uncertain . Purpose : To evaluate and compare the outcomes of mosaic-type osteochondral autologous transplantation ( OAT ) and microfracture ( MF ) procedures for the treatment of articular cartilage defects of the knee joint in young active athletes . This article represents an up date of the clinical results at 10 years . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Between 1998 and 2002 , a total of 60 athletes with a mean age of 24.3 years ( range , 15 - 40 years ) and with a symptomatic ACD or OCD in the knee were r and omized to undergo either OAT or MF . Patients were then evaluated postoperatively using the International Cartilage Repair Society ( ICRS ) score , Tegner activity score , radiographs , and magnetic resonance imaging . The mean follow-up time was 10.4 years ( range , 9 - 11 years ) . Results : Three to 10 years after the OAT and MF procedures , patients had lower ICRS and Tegner scores ( P < .05 ) , but both groups still had significant clinical improvement over presurgery scores according to ICRS scores at 10-year follow-up . Statistically significantly better results were detected in patients in the OAT group compared with those in the MF group at 10 years ( P < .005 ) . At 10-year follow-up , there were 15 failures ( 26 % ) , including 4 failures ( 14 % ) of the OAT and 11 failures ( 38 % ) of MF treatment ( P < .05 ) . Seven patients ( 25 % ) from the OAT group and 14 patients ( 48 % ) from the MF group had radiographic evidence of Kellgren-Lawrence grade I osteoarthritis at 10 years , but these differences were not significant ( P = .083 ) or related to the clinical results . The ICRS and Tegner scores of younger athletes ( < 25 years at the time of primary surgery ) remained significantly higher after 10 years compared with older patients ( P < .05 ) ; 15 of 20 patients ( 75 % ) in the OAT group and 8 of 22 patients ( 37 % ) in the MF group maintained the same physical activity level . Conclusion : The OAT technique for ACD or OCD repair in the athletic population allows for a higher rate of return to and maintenance of sports at the preinjury level compared with MF OBJECTIVE To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging ( MRI ) in patients with symptomatic knee osteoarthritis ( OA ) , and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression . METHODS Two hundred twenty-four men and women ( mean age 66 years ) were studied . Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup . Radiographs of the knee ( with weight-bearing ) were read for joint space narrowing ( scale 0 - 3 ) , with progression defined as any worsening in score . We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint , and defined cartilage loss as an increase in score ( scale 0 - 4 ) at any region . We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI , using a generalized estimating equation proportional odds logistic regression , adjusted for baseline cartilage score , age , body mass index , and sex . The medial and lateral compartments were analyzed separately . RESULTS In the medial compartment , 104 knees ( 46 % ) had cartilage loss detected by MRI . The adjusted odds ratio was 3.7 ( 95 % confidence interval 2.2 - 6.3 ) for radiographic progression being predictive of cartilage loss on MRI . However , there was still a substantial proportion of knees ( 80 of 189 [ 42 % ] ) with cartilage loss visible on MRI when no radiographic progression was apparent . Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region , but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss . Radiographic progression appeared specific ( 91 % ) but not sensitive ( 23 % ) for cartilage loss . Overall findings were similar for the lateral compartment . CONCLUSION While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI , radiography is not a sensitive measure , and if used alone , will miss a substantial proportion of knees with cartilage loss Objective The aim of this study was to compare the effect of a 12-wk exercise therapy program and arthroscopic partial meniscectomy on knee strength and functional performance in middle-aged patients with degenerative meniscus tears . Design A total of 82 patients ( mean age , 49 yrs ; 35 % women ) with a symptomatic , unilateral , magnetic resonance imaging – verified degenerative meniscus tear and no or mild radiographic osteoarthritis were r and omly assigned to a supervised neuromuscular and strength exercise program or arthroscopic partial meniscectomy . Outcomes assessed 3 mos after intervention initiation were isokinetic knee muscle strength , lower extremity performance , and self-reported global rating of change . Results Mean difference in isokinetic knee extension peak torque between the two groups was 16 % ( 95 % confidence interval , 7.1–24.0 ) ( P < 0.0001 ) , favoring the exercise group . Patients in the exercise group improved isokinetic knee extension peak by a mean of 25 Nm ( range , 18–33 Nm ) from baseline to follow-up . Furthermore , patients assigned to exercise therapy showed statistically significant improvements ( P ⩽ 0.002 ) in all other measured variables , with moderate to large effect sizes ( 0.5–1.3 ) . Patients reported a similar and positive effect of both interventions . Conclusion A 12-wk supervised exercise therapy program yielded clinical ly relevant and statistically significant improvement in isokinetic quadriceps strength immediately after completion of the program , as compared with treatment with arthroscopic partial meniscectomy Compare the medium-term effectiveness and tolerance between joint lavage ( JL ) in combination with triamcinolone hexacetonide ( TH ) intra-articular injection ( IAI ) and IAI with TH alone for treatment of primary osteoarthritis ( OA ) of the knee . A r and omized , double-blind , controlled study was carried out on 60 patients with primary OA of the knee , r and omized into two intervention groups : JL/TH group , joint lavage in combination with TH intra-articular injection and TH group , TH intra-articular injection . Patients were followed for 12 weeks by a blind observer using the following outcome measurements : visual analogue scale for pain at rest and in movement , goniometry , WOMAC , Lequesne ’s index , timed 50-ft walk , perception of improvement , Likert scale for improvement assessment , use of nonsteroidal anti-inflammatory drugs and analgesics , and local side effects . There were no statistical differences in the inter-group analysis for any of the variables studied over the 12-week period . Although both groups demonstrated statistical improvement in the intra-group evaluation ( except for Likert scale according to patient and the use of anti-inflammatory drugs ) . In the Kellgren – Lawrence scale ( KL ) 2 and 3 sub- analysis , there was a statistical difference regarding joint flexion among patients classified as KL 2 , favoring the TH group ( p = 0.03 ) . For the KL 3 patients , there were statistical differences favoring the JL/TH group regarding Lequesne ( p = 0.021 ) , WOMAC pain score ( p = 0.01 ) , and Likert scale according to the patient ( p = 0.028 ) and the physician ( p = 0.034 ) . The combination of joint lavage and IAI with TH was not more effective than IAI with TH alone in the treatment of primary OA of the knee . However , KL 3 patients may receive a major benefit from this combination OBJECTIVE To evaluate the efficacy of joint lavage and intraarticular steroid injection , alone and in combination , in the treatment of patients with symptomatic knee osteoarthritis ( OA ) . METHODS Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospect i ve , r and omized , controlled , 2 x 2 factorial- design trial of 6 months ' duration . The 4 treatment groups consisted of 1 ) intraarticular placebo ( 1.5 ml of 0.9 % normal saline ) , 2 ) intraarticular corticosteroids ( 3.75 mg of cortivazol in 1.5 ml ) , 3 ) joint lavage and intraarticular placebo , and 4 ) joint lavage and intraarticular corticosteroid . Outcome measures evaluated at baseline , week 1 , week 4 , week 12 , and week 24 included severity of pain ( 100-mm visual analog scale [ VAS ] ) , global status ( 100-mm VAS ) , and Lequesne 's functional index . RESULTS No interaction between steroid injection and joint lavage was demonstrated . Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 ( P = 0.020 ) . In contrast , corticosteroid injection had no long-term effect ( P = 0.313 ) ; corticosteroid injection was associated with a decrease in pain only at week 1 ( P = 0.003 ) and week 4 ( P = 0.020 ) . After week 4 , Lequesne 's functional index was not significantly improved regardless of the assigned treatment . CONCLUSION Compared with placebo , both treatments significantly relieved pain but did not improve functional impairment . The effects of the 2 treatments were additive . Cortivazol provided short-term relief of pain ( up to week 4 ) . The effects of joint lavage persisted up to week 24 Our aim was to compare the degree of patellar descent and alteration in angle of the inclination of the tibial plateau in lateral closing-wedge and medial opening-wedge high tibial osteotomy ( HTO ) in 51 consecutive patients with osteoarthritis of the medial compartment and varus malalignment . Patellar height was measured by the Insall-Salvati ( IS ) and the Blackburne-Peel ( BP ) ratios . The tibial inclination was determined by the Moore-Harvey ( MH ) method . Multivariate linear regression analysis was used to determine the influence of the type of HTO ( closing vs opening wedge ) on the post-operative patellar height or tibial inclination . The intra- and interobserver variability of these methods was determined before operation and at follow-up at one year . After an opening-wedge HTO the patellar height was significantly more decreased ( mean post-operative difference : IS = 0.15 ; 95 % confidence interval ( CI ) 0.06 to 0.23 ; BP = 0.11 ; 95 % CI 0.05 to 0.18 ) compared with a closing-wedge HTO . The angle of tibial inclination differed significantly ( mean post-operative difference MH = -6.40 degrees ; 95 % CI -8.74 to -4.02 ) between the two HTO techniques , increasing after opening-wedge HTO and decreasing after closing-wedge HTO . There was no clinical ly-relevant difference in the intra- and interobserver variability of measurements of patellar height either before or after HTO The purpose of this prospect i ve study was to determine whether or not abrasion arthroplasty promotes cartilage regeneration in osteoarthritic ( OA ) knees with eburnation . Patients with OA knees were divided into a group of 51 knees treated by osteotomy with abrasion arthroplasty ( Group A ) and another group of 37 knees treated by osteotomy alone ( Group B ) . Regeneration of cartilage was compared between the groups both arthroscopically and histologically . The Outerbridge classification was used for arthroscopic grading with Grade 0 being normal and Grade IV representing eburnation . On arthroscopic examination , around 12 months after surgery , Group A showed a significantly higher incidence of Grade II repair ( a smooth articular surface and small fissures ) and a lower incidence of Grade IV repair than Group B on both the femoral ( P < .001 ) and tibial ( P < .01 ) joint surfaces . Age was the only factor influencing the grade of tibial cartilage in Group A. Histological examination showed that 64 % of the regenerated tissue studied consisted of fibro-cartilage at around 12 months after surgery . There was no difference in the clinical outcome at 2 to 9 years postoperatively between Groups A and The purpose of the present study was to explore the efficacy of arthroscopic loose body removal for knee osteoarthritis ( KOA ) . A total of 23 patients with KOA were enrolled and r and omly received conservative treatment ( conservative group ; n=10 ) or loose body removal surgery ( surgery group ; n=13 ) . The serum levels of disease activity indices , including hypersensitive C-reactive protein ( hs-CRP ) , erythrocyte sedimentation rate ( ESR ) and synovial inflammatory factors [ interleukin (IL)-1 and IL-6 ] were detected prior to surgery , and at 4 days , 2 or 4 weeks after surgery . All patients were followed up for 2 years and the cure rate was estimated . No significant difference was identified in pre-operative plasma levels of hs-CRP and ESR as well as the synovial concentration of IL-1 and IL-6 between the two groups ( all P>0.05 ) . At 2 and 4 weeks after treatment , the levels of these parameters in the surgery group were significantly lower than those in the conservative group ( all P<0.05 ) , although the maximum value of these parameters was higher in the surgery group than in the conservative group at 4 days after surgery . The cure rate for KOA in the surgery group was significantly higher than that in the conservative group . In conclusion , the results demonstrated that arthroscopic loose body removal is a more effective treatment than conservative therapy for KOA The objective of this study was to evaluate the efficacy and safety of diacerein in early , symptomatic knee osteoarthritis in Indian population . Sixty-four patients of knee osteoarthritis fulfilling American College of Rheumatology Criteria were r and omized to receive either diacerein or placebo for 8 weeks , followed by 4 weeks “ treatment-free ” follow-up in this single-blind , parallel group , post-marketing trial . Primary efficacy variable was visual analogue scale ( VAS ) assessment of pain on movement ; secondary efficacy variables included Western Ontario and Mc Master Universities Osteoarthritis Index ( WOMAC ) subscores for stiffness and physical function , rescue medication use and physician 's clinical global impression ( CGI ) . Compared to placebo , diacerein showed highly significant ( p < 0.01 ) reductions in VAS pain scores , significant ( p < 0.05 ) reductions in WOMAC physical function scores , significantly lower requirement for rescue medication , and significantly better CGI grade s. Incidence of adverse events were significantly ( p < 0.01 ) higher in diacerein arm with urine discoloration and soft stool being the most common ones . However , most events were of mild to moderate intensity . In Indian patients with knee osteoarthritis , diacerein effectively reduces pain and improves physical function , and despite frequent adverse events , overall tolerability seemed to be good Two hundred patients with a meniscal lesion were peroperatively allocated to partial or total meniscectomy in a r and om manner . The results were compared at one year and at 6.3 to 9.8 years ( median 7.8 ) . After one year more patients with partial meniscectomy ( 90 % ) than with total meniscectomy ( 80 % ) had no complaints . At the later review these figures were 62 % and 52 % , respectively ( p = 0.18 ) . However , patients with partial meniscectomy had higher functional scores . The deterioration in function between the first review and the second showed no significant difference in the two treatment groups . The incidence of mediolateral instability rose from 8 % to 47 % and was more frequent after total than after partial meniscectomy . Between the two review s the radiological signs of knee degeneration increased with no difference between the two treatment groups SUMMARY Purpose : Joint lavage ( JL ) , involves the passage of cold sterile 0.9 % saline through the knee joint in order to have the fluid reach the inside of the joint capsule . This technique was evaluated as a local treatment for osteoarthritis ( OA ) of the knee alone ( JL ) and in combination with intra-articular infiltration with glucocorticoids ( JLC ) . Patients and methods : An overall 299 knees belonging to 205 patients ( 22 % males , 78 % females ) with a mean age of 67 ± 8 years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were r and omised in the ratio of 1:4 into two therapeutic groups , namely : JL ( n = 62 ) and JLC ( n = 237 ) . All patients received joint lavage on day 0 ; in those of the JLC group , joint lavage was followed by infiltration of 40 mg of triamcinolone acetonide . The efficacy of both treatments was assessed by recording the corresponding values for the following variables : pain strength as measured by a visual analogy scale ( VAS ) , effusion , crepitation , restricted motion , spontaneous pain , pain on pressure , pain on passive motion and pain on active motion ; all of these were recorded at the onset of the study , and after 1 and 3 months . Results : There were no significant differences in the values of the variables at the different follow-up times . Also , pain severity was similar in both treatment groups . Thus , VAS for pain was 7.3 ± 0.3 for the JL group and 7.1 ± 0.2 for the JLC group at the onset , and decreased to 3.0 ± 0.3 in the former and 2.8 ± 0.2 in the latter after 1 month ; the decrease was statistically significant in both cases . After 3 months , the JL and JLC groups had a VAS of 3.5 ± 0.3 and 3.8 ± 0.2 , respectively . Conclusions : The results of this work suggest the absence of significant differences between the two treatments , such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management of osteoarthritis of the knee OBJECTIVE Magnetic resonance imaging ( MRI ) has greater sensitivity to detect osteoarthritis ( OA ) damage than radiographs but it is uncertain which MRI findings in early OA are clinical ly important . We examined MRI abnormalities detected in knees without radiographic OA and their association with incident knee symptoms . METHOD Participants from the Multicenter Osteoarthritis Study ( MOST ) without frequent knee symptoms ( FKS ) at baseline were eligible if they also lacked radiographic features of OA at baseline . At 15 months , knees that developed FKS were defined as cases while control knees were drawn from those that remained without FKS . Baseline MRIs were scored at each subregion for cartilage lesions ( CARTs ) ; osteophytes ( OST ) ; bone marrow lesions ( BML ) and cysts . We compared cases and controls using marginal logistic regression models , adjusting for age , gender , race , body mass index ( BMI ) , previous injury and clinic site . RESULTS 36 case knees and 128 control knees were analyzed . MRI damage was common in both cases and controls . The presence of a severe CART ( P=0.03 ) , BML ( P=0.02 ) or OST ( P=0.02 ) in the whole knee joint was more common in cases while subchondral cysts did not differ significantly between cases and controls ( P>0.1 ) . Case status at 15 months was predicted by baseline damage at only two locations ; a BML in the lateral patella ( P=0.047 ) and at the tibial subspinous subregions ( P=0.01 ) . CONCLUSION In knees without significant symptoms or radiographic features of OA , MRI lesions of OA in only a few specific locations preceded onset of clinical symptoms and suggest that changes in bone play a role in the early development of knee pain . Confirmation of these findings in other prospect i ve studies of knee OA is warranted Abstract Purpose Studies comparing mid- or long-term outcomes of open- and closed-wedge high tibial osteotomy are limited . Here , the midterm survival rate and clinical and radiographic outcomes were compared for these two techniques . The study hypothesis , based on short-term follow-up , was that after midterm follow-up , the two techniques would not differ . Methods A prospect i ve follow-up study was conducted for a previously reported r and omized controlled trial of an original 50 patients ( 25 open-wedge osteotomy and 25 closed-wedge osteotomy ) with medial knee osteoarthritis and a varus leg alignment . We analyzed patients without knee arthroplasty ( mean age 48.7 years , SD 8.0 ) for clinical and radiographic follow-up . Results Five patients in each group had undergone conversion to a total knee arthroplasty or unicompartmental knee arthroplasty , leaving 19 patients for analysis in each group . At 7.9 years of follow-up ( range 7–9 years ) , survival did not differ significantly between groups ( open-wedge group 81.3 % [ 95 % confidence interval ( CI ) 75.2–100 ] , closed-wedge group 82.0 % [ 95 % CI 66.7–100 ] ) . At final follow-up , total Dutch Western Ontario and McMaster Universities Arthritis ( WOMAC ) , Knee Society Score , and visual analog scale ( VAS ) pain did not differ between groups . However , the results were significantly better in the closed-wedge group for VAS satisfaction and WOMAC pain and stiffness compared to the open-wedge group . Radiographic evaluation did not differ between groups for any outcome at final follow-up . Conclusion After a mean follow-up of 7.9 years , patients undergoing a closed-wedge osteotomy had favorable clinical results compared to those who underwent an open-wedge osteotomy . Level of evidence II Thirty-eight patients with symptomatic knee osteoarthritis without mechanical symptoms were r and omised after informed consent to receive either a course of intra-articular Hyalgan injections or an arthroscopic washout . The patients were prospect ively assessed pre-intervention , 6 weeks , 3 months , 6 months and 1 year using a 10 cm visual analogue pain score , the Knee Society function score and the Lequesne index . There was no significant difference between the two groups at 6 weeks , 3 months , 6 months or 1 year . The use of intra-articular Hyalgan injections in patients with knee osteoarthritis without mechanical symptoms gives results comparable with arthroscopic washout . Hyalgan is an alternative to arthroscopy in this patient group . Further study is needed to confirm these findings and improve patient selection Seventy-eight knee joints with varus malalignment were examined preoperatively using three-point measurement . Operation was performed with or without 5 degrees overcorrection of the varus deformity using r and om selection . The overcorrection group showed significantly better results than the normal-correction group Background : The quality of cartilage repair after marrow stimulation is unpredictable . To overcome the shortcomings of the microfracture technique , various augmentation techniques have been developed . However , their efficacies remain unclear . Hypothesis : The quality of cartilage repair and clinical outcomes would be superior in patients undergoing high tibial osteotomy ( HTO ) with microfracture and collagen augmentation compared to those undergoing HTO with microfracture alone without collagen augmentation for the treatment of medial compartment osteoarthritis ( OA ) of the knee . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : Twenty-eight patients undergoing HTO were r and omized into 2 groups : microfracture alone ( group 1 , n = 14 ) or microfracture with collagen augmentation ( group 2 , n = 14 ) . At 1 year postoperatively , second-look arthroscopic surgery and biopsy of repaired cartilage were performed at the time of HTO plate removal . Biopsy specimens were grade d using the International Cartilage Repair Society Visual Assessment Scale II ( ICRS II ) . In addition , imaging outcomes in terms of the magnetic resonance observation of cartilage repair tissue ( MOCART ) score were assessed based on magnetic resonance imaging ( MRI ) . Finally , clinical outcomes in terms of the visual analog scale ( VAS ) for pain score , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , International Knee Documentation Committee ( IKDC ) score , and Tegner activity scale score were evaluated . Results : The mean ICRS II score in group 2 was significantly higher than that in group 1 ( 1053.2 vs 885.4 , respectively ; P = .002 ) . Group 2 showed greater improvement in tissue morphology , cell morphology , surface architecture , middle/deep zone assessment , and overall assessment compared with group 1 ( P < .050 for all comparisons ) . Imaging outcomes based on the MOCART score were superior in group 2 compared to those in group 1 on MRI at 1 year postoperatively ( 64.6 vs 45.4 , respectively ; P = .001 ) . The degree of defect repair was better in group 2 than in group 1 ( P = .040 ) . Clinical outcomes in terms of the VAS for pain score , KOOS , IKDC score , and Tegner activity scale score were improved in both groups without between-group differences ( P > .100 for all comparisons ) . Conclusion : The quality of cartilage repair after microfracture with collagen augmentation was superior to that after microfracture alone in patients undergoing HTO . Clinical results after 1 year did not reflect this difference in tissue repair . Therefore , a longer follow-up of the cohort is needed to answer this question Objective Varus and valgus alignment are associated with progression of knee osteoarthritis , but their role in incident disease is less certain . Radiographic measures of incident knee osteoarthritis may be capturing early progression rather than disease development . The authors tested the hypothesis : in knees with normal cartilage morphology by MRI , varus is associated with incident medial cartilage damage and valgus with incident lateral damage . Methods In MOST , a prospect i ve study of persons at risk of or with knee osteoarthritis , baseline full-limb x-rays and baseline and 30-month MRI were acquired . In knees with normal baseline cartilage morphology in all tibiofemoral subregions , logistic regression was used with generalised estimating equations to examine the association between alignment and incident cartilage damage adjusting for age , gender , body mass index , laxity , meniscal tear and extrusion . Results Of 1881 knees , 293 from 256 persons met the criteria . Varus versus non-varus was associated with incident medial damage ( adjusted OR 3.59 , 95 % CI 1.59 to 8.10 ) , as was varus versus neutral , with evidence of a dose effect ( adjusted OR 1.38/1 ° varus , 95 % CI 1.19 to 1.59 ) . The findings held even excluding knees with medial meniscal damage . Valgus was not associated with incident lateral damage . Varus and valgus were associated with a reduced risk of incident lateral and medial damage , respectively . Conclusion In knees with normal cartilage morphology , varus was associated with incident cartilage damage in the medial compartment , and varus and valgus with a reduced risk of incident damage in the less loaded compartment . These results support that varus increases the risk of the initial development of knee osteoarthritis OBJECTIVE There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments . This r and omised controlled trial aim ed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy . METHOD 150 out of 179 eligible patients , aged 45 to 64 ( mean:54 ± 5 ) , symptom duration more than 3 months and st and ing X-ray with Ahlbäck grade 0 , were r and omised to : ( 1 ) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme ( non-surgery group ) ; or ( 2 ) the same as ( 1 ) plus , within 4 weeks of inclusion , knee arthroscopy for resection of any significant meniscal injuries ( surgery group ) . The primary outcome was change in pain at 12 months , assessed with the Knee Injury and Osteoarthritis Outcome Score ( KOOSPAIN ) . RESULTS In the Intention-To-Treat analysis , pain at 12 months was significantly lower in the surgery than in the non-surgery group . The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group ( between-group difference was 10.6 points of change ; 95 % CI : 3.4 to 17.7 , P = 0.004 ) . The As-Treated analysis results were consistent with the Intention-To-Treat analysis results . CONCLUSION Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme . Patients ' age or symptom history ( i.e. , mechanical symptoms or acute onset of symptoms ) did n't affect the outcome . TRIAL REGISTRATION NCT01288768 OBJECTIVE To compare arthroscopic surgery and closed-needle joint lavage for patients with non-end-stage osteoarthritis ( OA ) of the knee under controlled , experimental conditions . METHODS Thirty-two subjects who met specific clinical , radiologic , medical , and rehabilitation criteria were r and omized to receive arthroscopic surgery ( n = 18 ) or joint lavage ( n = 14 ) . Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 st and ard clinical parameters , self-reported pain and functional status ( by the Arthritis Impact Measurement Scales ) , 50-foot walk time , 2 global scales , and direct and indirect medical costs . RESULTS At 3 months of followup , there were no significant between-group differences in pain , self-reported and observed functional status , and patient and " blinded " physician global assessment s. The arthroscopic procedure cost $ 3,840 more than did closed-needle joint lavage . After 1 year , there were no between-group differences in medication costs , utilization of medical services , or indirect costs related to employment or use of household help . After 1 year , 44 % of subjects who underwent arthroscopy reported improvement and 58 % of subjects who underwent joint lavage improved . Patients with tears of the anterior two-thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement ( by " blinded " physician assessment ) after arthroscopic surgery ( 0.63 ) than did patients with other intraarticular pathology ( 0.20 ) . CONCLUSION The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non-end-stage OA of the knee who fail to respond to conservative therapy , but it may be beneficial for certain subgroups Background Damaged articular cartilage has limited capacity for self-repair . Autologous chondrocyte implantation using a characterized cell therapy product results in significantly better early structural repair as compared with microfracture in patients with symptomatic joint surface defects of the femoral condyles of the knee . Purpose To evaluate clinical outcome at 36 months after characterized chondrocyte implantation ( CCI ) versus microfracture ( MF ) . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Patients aged 18 to 50 years with single International Cartilage Repair Society ( ICRS ) grade III/IV symptomatic cartilage defects of the femoral condyles were r and omized to CCI ( n = 57 ) or MF ( n = 61 ) . Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score ( KOOS ) . Serial magnetic resonance imaging ( MRI ) scans were scored using the Magnetic resonance Observation of Cartilage Repair Tissue ( MOCART ) system and 9 additional items . Gene expression profile scores associated with ectopic cartilage formation were determined by RT-PCR . Results Baseline mean overall KOOS ( ±SE ) was comparable between the CCI and MF groups ( 56.30 ± 1.91 vs 59.46 ± 1.98 , respectively ) . Mean improvement ( ±SE ) from baseline to 36 months in overall KOOS was greater in the CCI group than the MF group ( 21.25 ± 3.60 vs 15.83 ± 3.48 , respectively ) , while in a mixed linear model analysis with time as a categorical variable , significant differences favoring CCI were shown in overall KOOS ( P = .048 ) and the subdomains of Pain ( P = .044 ) and QoL ( P = .036 ) . More CCI- than MF-treated patients were treatment responders ( 83 % vs 62 % , respectively ) . In patients with symptom onset of < 2 years , the mean improvement ( ±SE ) from baseline to 36 months in overall KOOS was greater with CCI than MF ( 24.98 ± 4.34 vs 16.50 ± 3.99 , respectively ) and even greater in patients with symptom onset of <3 years ( 26.08 ± 4.10 vs 17.09 ± 3.77 , respectively ) . Characterized chondrocyte implantation patients with high ( > 2 ) versus low ( < 2 ) gene profile scores showed greater improvement from baseline in mean overall KOOS ( ±SE ) at 36 months ( 28.91 ± 5.69 vs 18.18 ± 5.08 , respectively ) . Subchondral bone reaction significantly worsened over time with MF compared with CCI ( P < .05 ) . Conclusion Characterized chondrocyte implantation for the treatment of articular cartilage defects of the femoral condyles of the knee results in significantly better clinical outcome at 36 months in a r and omized trial compared with MF . Time to treatment and chondrocyte quality were shown to affect outcome Possibly the greatest threat to the success of a r and omized clinical trial is the inability to recruit an adequate number of subjects . Concern that the r and omized clinical trial will adversely affect the physician-patient relationship is the most common reason for physicians ' reluctance to enroll patients in such trials . We report a modification of a prer and omized design , first described by Zelen , which was implemented in a r and omized clinical trial of arthroscopy for patients who had osteoarthrosis of the knee . The method was associated with a sixfold increase in the rate of accrual of patients as compared with the use of a classic r and omization trial . We propose the design as a potential solution to the problem of recruitment of subjects , particularly for clinical studies INTRODUCTION Valgus tibial osteotomy ( VTO ) is a well-known procedure for the treatment of medial compartment femoro-tibial osteoarthritis . Good and very good results have been reported with calcium phosphate wedges , which avoid the inconveniences of autologous grafts use . The hypothesis of this study is that with equivalent results in the treatment of osteoarthritis of the knee , the use of calcium phosphate wedges ( BMC aPh ) to fill the bone defect created by osteotomy would result in fewer specific complications and less pain associated with autologous grafts ( AUTO ) harvesting . PATIENTS AND METHODS This prospect i ve , controlled , r and omised study included one arm that received a macroporous , biphasic calcium phosphate wedge ( BMC aPh group ) and one arm that received an autologous tricortical graft ( AUTO group ) for filling . The same plate with locked screws was used for fixation in all cases . All patients underwent at least two years of clinical and radiographic post-operative follow-up . RESULTS Forty patients were included . Loss of correction occurred in six of the twenty-two patients in the BMC aPh group ( 27 % ) , result ing in three early surgical revisions , compared to one loss of correction in the AUTO group . Lateral cortical hinge tears were a risk factor for loss of correction for the entire cohort and in the BMC aPh group . ( relative risk 13.3 [ 1.9 - 92 ] . Moreover , union took significantly longer and pain lasted significantly longer in the BMC aPh group , although results were comparable at 6 months . DISCUSSION A significant number of undesirable events ( loss of correction ) occurred in this study , limiting the number of included patients . Nevertheless , the results show that although there was no difference in the two groups for overall complications , number of revisions all causes combined , or clinical results , filling with BMC aPh was less tolerated and increased the risk of loss of correction when local mechanical conditions of the knee were unfavourable ( lateral cortical hinge tears ) . Moreover , although it is not possible to draw a conclusion because of methodology bias in this study , early weight-bearing resumption on the knee also seemed to favour these complications . LEVEL OF EVIDENCE Level II . Prospect i ve r and omized study The clinical outcome of patients treated either by high tibial osteotomy or unicompartmental arthroplasty for medial unicompartmental osteoarthritis of the knee was compared in a prospect i ve r and omised study . In total , 32 patients received a high tibial osteotomy ( HTO ) and 28 patients a unicompartmental arthroplasty ( UKA ) . More intra- and postoperative complications were observed after HTO . Patients were assessed at an average of 2.5 ( 1.6 - 5 ) , 4.5 ( 3.6 - 7 ) , and 7.5 years ( 6.6 - 10 ) after the operation . Using the Knee Society Score , 71 % ( 15 ) of patients after osteotomy and 65 % ( 13 ) after replacement had a knee score of excellent or good 7 - 10 years postoperatively . The Kaplan-Meier survival analysis 7 - 10 years postoperatively showed a survivorship of 77 % for UKA and 60 % for HTO . Although the unicompartmental prosthesis used in this series has not shown promising results , we conclude that with the advanced design of unicompartmental prosthesis today , UKA offers better long-term success BACKGROUND Varus deformity increases the risk of progression of medial compartment knee osteoarthritis . The aim of this study was to investigate the clinical and radiographic mid-term results of closing-wedge and opening-wedge high tibial osteotomy when used to treat this condition . METHODS From January 2001 to April 2004 , ninety-two patients were r and omized to receive either a closing-wedge or an opening-wedge high tibial osteotomy . The clinical outcome and radiographic results were examined preoperatively ; at one year ; and , for the present study , at six years postoperatively . The outcomes that we review ed included maintenance of the achieved correction , progression of osteoarthritis ( based on the Kellgren and Lawrence classification ) , severity of pain ( as assessed on a visual analog scale [ VAS ] ) , knee function ( as measured with the Hospital for Special Surgery [ HSS ] score and Knee injury and Osteoarthritis Outcome Score [ KOOS ] ) , walking distance , complications , and survival with conversion to a total knee arthroplasty as the end point . The results were analyzed on the basis of the intention-to-treat principle . RESULTS Six years postoperatively , the mean hip-knee-ankle ( HKA ) angle ( and st and ard deviation ) was 3.2 ° ± 4.1 ° of valgus after a closing-wedge high tibial osteotomy and 1.3 ° ± 5.0 ° of valgus after an opening-wedge high tibial osteotomy ( p = 0.343 ) . In both groups , the six-year postoperative HKA angles did not differ from the respective one-year postoperative angles . No difference in the severity of pain or in knee function was found between the two groups . Four complications ( 9 % ) occurred in the closing-wedge group and seventeen ( 38 % ) , in the opening-wedge group . Ten ( 22 % ) of the patients in the closing-wedge group and three ( 8 % ) in the opening-wedge group needed conversion to a total knee arthroplasty within the six-year period ( p = 0.05 ) . The difference in the percentage of cases with conversion to total knee arthroplasty was 14 % ( 95 % confidence interval [ CI ] = 21.7 to 0.2 ) . CONCLUSIONS In the group of patients without conversion to a total knee arthroplasty , there was no difference between the high tibial closing-wedge and opening-wedge osteotomies in terms of clinical outcomes or radiographic alignment at six years postoperatively . Opening-wedge osteotomy was associated with more complications , but closing-wedge osteotomy was associated with more early conversions to total knee arthroplasty . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence OBJECTIVES Virtually all early cases of knee osteoarthritis have degenerative medial meniscus lesions accompanying the chondral defects on MRI . It is difficult to determine if the symptoms are caused by the unstable meniscus or by osteoarthritis , hence unclear guidance towards treatment . We , therefore , aim ed to determine the clinical improvement following arthroscopic meniscectomy compared to intraarticular administration of corticosteroids for degenerative ruptures of the medial meniscus in the presence of early stage medial compartment knee osteoarthritis . PATIENTS AND METHODS We included 120 consecutive cases of nontraumatic symptomatic knees which had degenerative lesions of the medial compartment ( cartilage and meniscus ) on MRI 's . They were r and omized to receive either intraarticular steroid injection or arthroscopic debridement . We also analyzed the correlation between BMI , age , gender , MRI , intraoperative aspect of the meniscus and cartilage and clinical improvement using the Oxford Knee Score up to one year . At one month there was significant improvement of the scores for all the examined cases . Also at one month , the arthroscopic group performed better in terms of symptom improvement . This was maintained for 79 % of the knees in the arthroscopic group and 61 % in the intraarticular steroid injection respectively , out of those available for follow up at one year . RESULTS At one month , symptoms reappeared for 12 patients in the steroid group and 7 in the arthroscopy respectively . Gender and age did not correlate with treatment , whereas extrusion of the meniscus , bone marrow edema , duration of the clinical symptoms , obesity and a low preoperative score were negative prognostic factors . CONCLUSIONS Degenerative medial meniscal tears , in the presence of osteoarthritis , can only marginally benefit from arthroscopic debridement over intraarticular steroid injections in short term follow up . When considering individual cases , factors become more predictive when analyzed in group Summary A double-blind trial with cartilage and bone-marrow extract ( Rumalon A ) and placebo ( Rumalon B ) was carried out on 106 patients with degenerative bilateral gonarthrosis . Favorable results were obtained in 64 % of the patients treated with Rumalon A and in only 29 % of the placebo group . This difference is statistically significant ( p < 0.05 ) . The slight influence of placebo can be related to the psychosomatic effect of injections and /or coincident spontaneous improvement of the gonarthrosis . Cartilage and bone marrow extract increases the therapeutic possibilities in degenerative joint disease . It is easy to administer and practically without side effects Abstract In this prospect i ve study high tibial osteotomy for medial gonarthrosis was performed in 95 patients ( 105 knee joints ) . The patients underwent simultaneously diagnostic and operative arthroscopic surgery of the knee joint . A follow-up arthroscopic examination could be performed in 75 patients ( 85 knee joints ) at the time of implant removal . In group 1 ( 20 knee joints ) , the osteotomy was performed after diagnostic arthroscopy without arthroscopic operation of the knee joint . The fixation of the osteotomy was accomplished by staples , postoperative plaster fixation and physiotherapy . In group 2 ( 20 knee joints ) , osteotomy was performed without additional operative arthroscopy after diagnostic arthroscopy , internal fixation by AOT-plate , no external fixation postoperatively and physiotherapy . In group 3 ( 22 knee joints ) , osteotomy was performed with additional operative arthroscopy ( Pridie drilling ) , internal fixation by AOT-plate no external fixation postoperatively no external fixation , physiotherapy and continuous passive motion . In group 4 ( 23 knee joints ) , osteotomy was performed with additional operative arthroscopy ( abrasio-arthroplasty ) , internal fixation by AOT-plate , no external fixation postoperatively , physiotherapy and continuous passive motion . All patients underwent arthroscopic examination of the knee with cartilage biopsies taken from three different regions of the femoral condyle during the same operative session as the osteotomy . At follow-up arthroscopy cartilage biopsies were taken from the same regions . There was no great difference in clinical outcome after 1 year between all groups . Arthroscopy as well as routine and electron microscopy showed better cartilage regeneration in groups 3 and 4 . Groups 1 and 2 showed only regeneration isles , sometimes not well fixed to the underlying bone , while in groups 3 and 4 cartilage regeneration was thicker and more stable , sometimes covering all of the pre-existing erosions . Therefore , we recommend osteotomy of the tibia for osteoarthritis together with operative arthroscopy in the same operative session Degeneration of the meniscus and the articular cartilage in unicompartmental osteoarthritis of the knee results in progressive deformity of the leg axis . It is the aim of this study to evaluate if a leg axis correction can be achieved by implanting a customised metallic interpositional device for the knee ( ConforMIS iForma ™ ) . Before and after implanting a ConforMIS iForma ™ knee implant , a radiological analysis of the leg axis deviation in the frontal plane was performed prospect ively in 27 patients by evaluating anteroposterior single-leg stance radiographs . We achieved a sufficient leg axis correction with an average correction of 3.8 ° and an averaged small under-adjustment of 0.9 ° by inserting the ConforMIS iForma ™ interpositional knee implant . Apart from the primary treatment objective of articular surface restitution the ConforMIS iForma ™ knee implant can be reliably used to correct axis deformity occurring with unicompartmental osteoarthritis of the knee . RésuméLa déformation progressive du membre inférieur entraîne lorsqu’existe une arthrose mono-compartimentale un dégénérescence du ménisque et du cartilage articulaire homolatéral . Le but de cette étude est d’évaluer la correction d’axe par un implant métallique d’interposition au niveau du genou(ConforMIS iForma ™ ) . avant et après implantation de l’implant ConforMIS iForma ™ une analyse radiologique prospect i ve de la déviation des membres dans le plan frontal a été réalisée , chez 27 patients avec radiographies de face et de profil . il est possible grâce à ce matériel d’avoir une correction moyenne de 3,8 ° avec une hypo correction de 0,9 ° . compte-tenu de l’objectif que nous nous étions fixés , l’utilisation de cet implant ( ConforMIS iForma ™ ) au niveau du genou , permet d’avoir une correction fiable de l’axe lorsque l’on traite des athroses mono-compartimentales OBJECTIVE To compare the efficacy of arthroscopic lavage plus corticosteroids ( ALC ) , arthroscopic lavage plus placebo ( ALP ) , and joint aspiration plus corticosteroids ( JAC ) in patients with arthritis of the knee , and to identify clinical or histological factors that predict outcome . DESIGN Prospect i ve , r and omised . METHOD Patients with arthritis of the knee ( not due to gout , osteoarthritis or septic arthritis ) were r and omised to 1 of 3 treatment arms : ALC , ALP or JAC . The primary endpoint was time to recurrence ; recurrence was defined as recurrent or persistent symptomatic knee swelling requiring local treatment , and /or non-improvement in knee joint score . Synovial tissue specimens were collected for histological analysis . RESULTS Of the 78 patients enrolled , 3 did not receive the intended therapy and 3 were lost to follow-up . The median time to recurrence was 9.6 months in the ALC group , 3.0 months in the JAC group and 1.0 month in the ALP group . Compared with ALC , the relative risk of recurrence of arthritis ( RR ) was 2.2 for JAC ( 95 % CI : 1.2 - 4.2 ; p = 0.02 ) and 4.7 for ALP ( 95 % CI : 2.3 - 9.4 ; p < 0.0001 ) . In the ALC group , extensive synovial fibrosis was associated with a higher risk of recurrence ( RR 5 - 7 ; 95 % CI : 1.6 - 20.5 ; p < 0.01 ) . CONCLUSION Arthroscopic lavage plus corticosteroids was more effective than arthroscopic lavage plus placebo or joint aspiration plus corticosteroids . The absence of synovial fibrosis predicted a beneficial response Valgus high tibial osteotomy for osteoarthritis of the medial compartment of the knee can be performed using medial opening- and lateral closing-wedge techniques . The latter have been thought to offer greater initial stability . We measured and compared the stability of opening- and closing-wedge osteotomies fixed by TomoFix plates using radiostereometry in a series of 42 patients in a prospect i ve , r and omised clinical trial . There were no differences between the opening- and closing-wedge groups in the time to regain knee function and full weight-bearing . Pain and knee function were significantly improved in both groups without any differences between them . All the osteotomies united within one year . Radiostereometry showed no clinical ly relevant movement of bone or differences between either group . Medial opening-wedge high tibial osteotomy secured by a TomoFix plate offers equal stability to a lateral closing-wedge technique . Both give excellent initial stability and provide significantly improved knee function and reduction in pain , although the opening-wedge technique was more likely to produce the intended correction BACKGROUND Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis , but it is unclear how the procedure achieves this result . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee . METHODS A total of 180 patients with osteoarthritis of the knee were r and omly assigned to receive arthroscopic débridement , arthroscopic lavage , or placebo surgery . Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope . Patients and assessors of outcome were blinded to the treatment-group assignment . Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores -- three on scales for pain and two on scales for function-- and one objective test of walking and stair climbing . A total of 165 patients completed the trial . RESULTS At no point did either of the intervention groups report less pain or better function than the placebo group . For example , mean ( + /-SD ) scores on the Knee-Specific Pain Scale ( range , 0 to 100 , with higher scores indicating more severe pain ) were similar in the placebo , lavage , and débridement groups : 48.9+/-21.9 , 54.8+/-19.8 , and 51.7+/-22.4 , respectively , at one year ( P=0.14 for the comparison between placebo and lavage ; P=0.51 for the comparison between placebo and débridement ) and 51.6+/-23.7 , 53.7+/-23.7 , and 51.4+/-23.2 , respectively , at two years ( P=0.64 and P=0.96 , respectively ) . Furthermore , the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinical ly meaningful difference . CONCLUSIONS In this controlled trial involving patients with osteoarthritis of the knee , the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure In a prospect i ve r and omised trial 76 knees with isolated degenerative changes in the medial femoral condyle of grade s 3 or 4 were treated by either arthroscopic debridement ( 40 ) or washout ( 36 ) . All knees were followed up for at least one year and 58 for five years . The mean follow-up time was 4.5 years in the debridement group and 4.3 years in the washout group . At one year 32 of the debridement group and five of the washout group were painfree and at five years 19 of a total of 32 survivors in the debridement group and three of the 26 in the washout group were also free from pain . The mean improvement in a modified Lysholm score was 28 for the debridement group at one year and 21 at five years . In the washout group it was only 5 at one year and 4 at five years . For knees with lesions of the medial femoral condyle of grade s 3 or 4 , arthroscopic debridement appears to be the treatment of choice with over half the patients free from pain after five years Arthroscopic knee joint lavage is used when conservative treatment of knee osteoarthritis is unsatisfactory and a joint prosthesis is not yet indicated . The potentially negative effect of irrigation fluids on cartilage metabolism and structure has led to the development of a temporary synovial fluid substitute containing hyaluronic acid . The short and long-term effects of this synovial fluid substitute were investigated in a total of 80 patients with persistent knee pain . Forty patients underwent arthroscopic knee joint lavage , in some cases combined with careful cartilage debridement ( group A ) while a further 40 patients underwent the same procedure which , after final joint lavage , was immediately followed by a single instillation of 10 ml of the synovial fluid substitute ( 0.5 % sodium hyaluronate ) into the joint ( A + HA group ) . After the procedure , pain on walking and restricted ability to walk 100 m were markedly reduced to a comparable extent in both groups . Three months later , the effect of the treatment assessed using various parameters ( CGI , restricted ability to walk 100 m , pain on walking , night pain ) had decreased in group A , while it remained stable or even improved slightly in the A + HA group . The Mann – Whitney statistics revealed a descriptive superiority for the A + HA group at this time point . One year after treatment the superiority of the A + HA group was confirmed using the same assessment parameters . No side effects or adverse events were observed for either treatment procedure . This study shows that arthroscopic knee joint lavage leads to a lasting improvement in pain and functional impairment . The post-arthroscopic instillation of a HA-based synovial fluid substitute into the joint is a suitable way of achieving long-term stabilisation of the treatment outcome . This was supported by findings of a survey of 66 patients at 2 years after treatment in this study . Level I prospect i ve , r and omised controlled double-blind study OBJECTIVE First , to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen ( as defined by the American College of Rheumatology ( ACR ) 1995 guidelines ) as measured by vali date d disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis ( OA ) of the knee . Second , to utilize the measures of effectiveness and costs in an economic evaluation ( see accompanying manuscript ) . DESIGN A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospect i ve , r and omized , open-label , 1-year , multi-centred trial , conducted in Canada . Patients were r and omized to ' Appropriate care with hylan G-F 20 ' ( AC+H ) or ' Appropriate care without hylan G-F 20 ' ( AC ) . Data were collected at clinic visits ( baseline , 12 months ) and by telephone ( 1 , 2 , 4 , 6 , 8 , 10 , and 12 months ) . RESULTS The AC+H group was superior to the AC group for all primary ( % reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain scale : 38 % vs 13%,P = 0.0001 ) and secondary effectiveness outcome measures . These differences were all statistically significant and exceeded the 20 % difference between groups set a priori by the investigators as the minimum clinical ly important difference . Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain , stiffness and physical function ( all P < 0.0001 ) , the SF-36 aggregate physical component ( P < 0.0001 ) and the Health Utilities Index Mark 3 ( HUI3 ) overall health utility score ( P < 0.0001 ) . Safety ( adverse events and patient global assessment s of side effects ) differences favoured the AC+H group . CONCLUSION The data presented here indicate that the provision to patients with knee OA of viscosupplementation with hylan G-F 20 within an appropriate care treatment regimen provides benefits in the knee , overall health and health related quality of life at reduced levels of co-therapy and systemic adverse reactions OBJECTIVE In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools , integrating expert readers ' experience with all available scoring tools and the published data comparing the different scoring systems , we iteratively developed the magnetic resonance imaging ( MRI ) Osteoarthritis Knee Score ( MOAKS ) . The purpose of this report is to describe the instrument and its reliability . METHODS The MOAKS instrument refines the scoring of bone marrow lesions ( BMLs ) ( providing regional delineation and scoring across regions ) , cartilage ( sub-regional assessment ) , and refines the elements of meniscal morphology ( adding meniscal hypertrophy , partial maceration and progressive partial maceration ) scoring . After a training and calibration session two expert readers read MRIs of 20 knees separately . In addition , one reader re-read the same 20 MRIs 4 weeks later presented in r and om order to assess intra-rater reliability . The analyses presented here are for both intra- and inter-rater reliability ( calculated using the linear weighted kappa and overall percent agreement ) . RESULTS With the exception of inter-rater reliability for tibial cartilage area ( kappa=0.36 ) and tibial osteophytes ( kappa=0.49 ) ; and intra-rater reliability for tibial BML number of lesions ( kappa=0.54 ) , Hoffa-synovitis ( kappa=0.42 ) all measures of reliability using kappa statistics were very good ( 0.61 - 0.8 ) or reached near-perfect agreement ( 0.81 - 1.0 ) . Only intra-rater reliability for Hoffa-synovitis , and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement < 75 % . CONCLUSION MOAKS scoring shows very good to excellent reliability for the large majority of features assessed . Further iterative development and research will include assessment of its validation and responsiveness The reasons why many patients seemingly benefit from arthroscopic treatment of osteoarthritis of the knee remain obscure . The purpose of this pilot study was to determine if a placebo effect might play a role in arthroscopic treatment of this condition . After giving full informed consent , including full knowledge of the pos sibility and nature of a placebo surgery , five subjects were r and omized to a placebo arthroscopy group , three subjects were r and omized to an arthroscopic lavage group , and two subjects were r and omized to a st and ard arthroscopic debridement group . The physi cians performing the postoperative assessment and the patients remained blinded as to treatment . Patients who received the placebo surgery reported decreased frequency , intensity , and duration of knee pain . They also thought that the procedure was worthwhile and would recommend it to family and friends . Thus , there may be a significant placebo effect for arthroscopic treatment of osteoarthritis of the knee . The small num bers in this preliminary study preclude a valid statistical analysis , and no conclusions can be drawn regarding the superiority of one treatment over another . A larger study is needed to evaluate fully the efficacy of an arthroscopic procedure for this condition and to decide if it is reasonable to expend health care re sources OBJECTIVE To compare the efficacy of arthroscopic lavage plus administration of corticosteroids ( ALC ) , arthroscopic lavage plus administration of placebo ( ALP ) , and joint aspiration plus administration of corticosteroids ( JAC ) in knee arthritis , and to evaluate whether clinical or histologic characteristics determine outcome . METHODS Patients with knee arthritis ( not due to gout , osteoarthritis , or septic arthritis ) were r and omized over 3 treatment arms : ALC , ALP , and JAC . The primary end point was event-free survival , with events defined as 1 ) recurrence or persistence of symptomatic knee swelling necessitating local re-treatment , or 2 ) nonimprovement of the knee joint score . Synovial tissue specimens were collected and analyzed histologically to identify predictive factors of responsiveness . RESULTS A total of 78 patients were enrolled ; 3 patients did not receive their allocated therapy and 3 were lost to followup . The median time until recurrence was 9.6 months after ALC , 3.0 months after JAC , and 1.0 month after ALP , corresponding to a relative risk ( RR ) of arthritis recurrence of 2.2 for JAC ( 95 % confidence interval [ 95 % CI ] 1.2 - 4.2 , P = 0.02 ) and 4.7 for ALP ( 95 % CI 2.3 - 9.4 , P < 0.0001 ) compared with ALC . A high versus low synovial extent of fibrosis conferred an RR for recurrence of 5.7 ( 95 % CI 1.6 - 20.5 , P < 0.01 ) after ALC . CONCLUSION Arthroscopic lavage plus administration of corticosteroids was more effective than arthroscopic lavage plus administration of placebo or joint aspiration plus injection of corticosteroids . The absence of fibrosis was a histologic predictor of a beneficial response OBJECTIVES We evaluated the efficacy of viscosupplementation with low- or high-molecular-weight hyaluronic acid ( HA ) preparations following arthroscopic debridement ( AD ) in patients with osteoarthritis of the knee . METHODS The study included 45 patients ( 19 men , 26 women ; mean age 53 years ; range 41 to 66 years ) with Kellgren-Lawrence grade 2 - 3 osteoarthritis of the knee . Following AD , the patients were r and omized to three groups to receive three intra-articular injections of 2 ml hylan G-F 20 ( Synvisc , n=16 ) , five intra-articular injections of 2 ml sodium hyaluronate ( Hyalgan , n=14 ) , and no injections ( controls , n=15 ) . Injections were administered at one-week intervals . All the patients were evaluated with pain , stiffness , and functional capacity scores of the WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index before and 6 and 12 months after AD . RESULTS Two patients and three patients complained of transient pain in Synvisc and Hyalgan groups , respectively . WOMAC scores showed significant decreases in all the groups at 6 and 12 months . There were no significant differences between the three groups with respect to improvement in WOMAC scores at 6 months . However , compared to the control group , differences between pre- and posttreatment scores at 12 months were significantly greater in the Synvisc ( p=0.004 ) and Hyalgan ( p=0.003 ) groups , with no significant difference between the two HA groups ( p>0.05 ) . CONCLUSION Our findings show that AD is beneficial in osteoarthritis of the knee in patients with appropriate indications , viscosupplementation increases the efficacy of treatment , and that low- and high-molecular-weight HA preparations have similar efficacy The aim of this prospect i ve follow-up study was to determine if gait measurements and /or clinical measurements could detect differences in treatment outcome between two surgical interventions in patients with knee osteoarthritis ( OA ) . The patients were followed for 5 years after surgery . Forty patients , 55 - 70 years of age , with unilateral knee OA were included . The patients were treated either with a high tibial osteotomy ( HTO ) ( n=18 ) or a unicompartmental knee arthroplasty ( UKA ) ( n=22 ) . Clinical outcome measures were the British Orthopaedic Association ( BOA ) score , pain during walking , passive range of knee motion ( PROM ) and patients ' subjective opinion . The gait variables were free walking speed , step frequency , step length and single and double-stance phase for each leg . The patients were examined before surgery and 3 months , 1 year and 5 years after surgery . The time-distance variables of gait could detect differences in treatment outcome , 3 months after surgery , while the clinical outcome measures , as given here , could not detect any differences between the two groups of patients . Measurements of free walking speed could be recommended for clinical evaluation , after surgical interventions , in patients with knee OA BACKGROUND New methods have been used , with promising results , to treat full-thickness cartilage defects . The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a r and omized trial . We are not aware of any previous r and omized studies comparing these methods . METHODS Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture ( forty in each group ) . We used the International Cartilage Repair Society , Lysholm , Short Form-36 ( SF-36 ) , and Tegner forms to collect data . An independent observer performed a follow-up examination at twelve and twenty-four months . Two years postoperatively , arthroscopy with biopsy for histological evaluation was carried out . The histological evaluation was done by a pathologist and a clinical scientist , both of whom were blinded to each patient 's treatment . RESULTS In general , there were small differences between the two treatment groups . At two years , both groups had significant clinical improvement . According to the SF-36 physical component score at two years postoperatively , the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group ( p = 0.004 ) . Younger and more active patients did better in both groups . There were two failures in the autologous chondrocyte implantation group and one in the microfracture group . No serious complications were reported . Biopsy specimens were obtained from 84 % of the patients , and histological evaluation of repair tissues showed no significant differences between the two groups . We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale . CONCLUSIONS Both methods had acceptable short-term clinical results . There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point . LEVEL OF EVIDENCE Therapeutic study , Level I-1a ( r and omized controlled trial [ significant difference ] ) . See Instructions to Authors for a complete description of levels of evidence BACKGROUND Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain . METHODS We conducted a multicenter , r and omized , controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging . We r and omly assigned 351 patients to surgery and postoperative physical therapy or to a st and ardized physical-therapy regimen ( with the option to cross over to surgery at the discretion of the patient and surgeon ) . The patients were evaluated at 6 and 12 months . The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) physical-function score ( ranging from 0 to 100 , with higher scores indicating more severe symptoms ) 6 months after r and omization . RESULTS In the intention-to-treat analysis , the mean improvement in the WOMAC score after 6 months was 20.9 points ( 95 % confidence interval [ CI ] , 17.9 to 23.9 ) in the surgical group and 18.5 ( 95 % CI , 15.6 to 21.5 ) in the physical-therapy group ( mean difference , 2.4 points ; 95 % CI , -1.8 to 6.5 ) . At 6 months , 51 active participants in the study who were assigned to physical therapy alone ( 30 % ) had undergone surgery , and 9 patients assigned to surgery ( 6 % ) had not undergone surgery . The results at 12 months were similar to those at 6 months . The frequency of adverse events did not differ significantly between the groups . CONCLUSIONS In the intention-to-treat analysis , we did not find significant differences between the study groups in functional improvement 6 months after r and omization ; however , 30 % of the patients who were assigned to physical therapy alone underwent surgery within 6 months . ( Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; METEOR Clinical Trials.gov number , NCT00597012 . ) BACKGROUND The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown . METHODS We conducted a single-center , r and omized , controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee . Patients were r and omly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone . The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) score ( range , 0 to 2400 ; higher scores indicate more severe symptoms ) at 2 years of follow-up . Secondary outcomes included the Short Form-36 ( SF-36 ) Physical Component Summary score ( range , 0 to 100 ; higher scores indicate better quality of life ) . RESULTS Of the 92 patients assigned to surgery , 6 did not undergo surgery . Of the 86 patients assigned to control treatment , all received only physical and medical therapy . After 2 years , the mean ( + /-SD ) WOMAC score for the surgery group was 874+/-624 , as compared with 897+/-583 for the control group ( absolute difference [ surgery-group score minus control-group score ] , -23+/-605 ; 95 % confidence interval [ CI ] , -208 to 161 ; P=0.22 after adjustment for baseline score and grade of severity ) . The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6 , respectively ( absolute difference , -0.2+/-11.1 ; 95 % CI , -3.6 to 3.2 ; P=0.93 ) . Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery . CONCLUSIONS Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy . ( Clinical Trials.gov number , NCT00158431 . PURPOSE The purpose of this study was to evaluate the efficacy of periarticular multimodal drug injection after medial opening-wedge high tibial osteotomy regarding the postoperative pain level . METHODS From January 2011 to January 2012 , 70 patients underwent medial opening-wedge high tibial osteotomy . Thirty-five patients were r and omly assigned to receive no injection ( group I ) , and 35 patients were assigned to receive periarticular multimodal drug injection ( group II ) . These 2 groups were compared regarding the postoperative pain level , frequency of additional nonsteroidal anti-inflammatory drug injections , total amount of patient-controlled analgesia , and number of times that patients pushed the patient-controlled analgesia button at each time interval . Statistical results were based on multivariate analysis of variance and repeated- measures analyses . RESULTS Multivariate analysis of variance of mean visual analog scale ( VAS ) scores over the 2-week postoperative period showed statistical significance ( P < .001 ) . Repeated- measures analysis yielded a statistically significant difference ( P = .001 ) for the time-by-treatment interaction , showing a clear periarticular multimodal drug injection benefit over time based on VAS scores . In addition , the mean number of times that patients pushed the patient-controlled analgesia button differed significantly between groups over time ( P = .01 ) . The VAS scores , frequency of additional nonsteroidal anti-inflammatory drug injections , mean number of times that patients pushed the patient-controlled analgesia button , and mean total amount of fentanyl consumption differed significantly within each group over time ( P < .001 for all variables ) . However , the frequency of additional nonsteroidal anti-inflammatory drug injections and mean total amount of fentanyl consumption did not differ significantly between groups over time ( P = .822 , P = .529 , and P = .282 ) . Opioid- and injection-related complications were not found . CONCLUSIONS This prospect i ve r and omized study shows that intraoperative periarticular multimodal drug injections in patients undergoing medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee could result in significant reductions in VAS scores at 2 weeks postoperatively . LEVEL OF EVIDENCE Level I , high- quality r and omized controlled trial with statistically significant differences Background As the natural healing capacity of damaged articular cartilage is poor , joint surface injuries are a prime target for regenerative medicine . Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo . Purpose To determine whether , in symptomatic cartilage defects of the femoral condyle , structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial . Patients aged 18 to 50 years were r and omized to characterized chondrocyte implantation ( n = 57 ) or microfracture ( n = 61 ) . Structural repair was blindly assessed in biopsy specimens taken at 1 year using ( 1 ) computerized histomorphometry and ( 2 ) evaluation of overall histological components of structural repair . Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score . Adverse events were recorded throughout the study . Results Characterized chondrocyte implantation result ed in better structural repair , as assessed by histomorphometry ( P = .003 ) and overall histologic evaluation ( P = .012 ) . Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation . Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage . Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score ( 56.30 ± 13.61 and 59.53 ± 14.95 for microfracture and characterized chondrocyte implantation , respectively ) , which increased in both groups to 70.56 ± 12.39 and 72.63 ± 15.55 at 6 months , 73.26 ± 14.66 and 73.10 ± 16.01 at 12 months , and 74.73 ± 17.01 and 75.04 ± 14.50 at 18 months , respectively . Both techniques were generally well tolerated ; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture . Conclusion One year after treatment , characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture . Short-term clinical outcome was similar for both treatments . The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation . Long-term follow-up is needed to confirm these findings |
11,242 | 32,205,551 | Conclusions : In adults undergoing cardiac surgery with cardiopulmonary bypass , the class of volatile anesthetics was superior to propofol with regard to long-term mortality , as well as to many secondary outcomes indicating myocardial protection .
Although early postoperative mortality did not differ significantly between the anesthetic groups , 1-yr mortality was significantly lower in the patients who received volatile anesthetics .
Additionally patients in the volatile anesthetic group had significantly lower occurrence of perioperative myocardial infa rct ion and troponin release and had higher postoperative cardiac index . | Background : The aim of this systematic review and meta- analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality ( primary outcomes ) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass . | Background The present study investigated the effects of propofol , desflurane , and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients . High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50 % with impaired length-dependent regulation of myocardial function . Methods Coronary surgery patients ( n = 45 ) were r and omly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane . Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter . Perioperatively , a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle . Response to increased cardiac load , obtained by leg elevation , was assessed before and after cardiopulmonary bypass ( CPB ) . Effects on contraction were evaluated by analysis of changes in dP/dtmax . Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation . Postoperative levels of cardiac troponin I were followed for 36 h. Results After CPB , cardiac index and dP/dtmax were significantly lower in patients under propofol anesthesia . Post-CPB , leg elevation result ed in a significantly greater decrease in dP/dtmax in the propofol group , whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB . After CPB , load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group . Troponin I levels were significantly higher in the propofol group . Conclusions Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively BACKGROUND Whether remote ischemic preconditioning ( transient ischemia and reperfusion of the arm ) can improve clinical outcomes in patients undergoing coronary-artery bypass graft ( CABG ) surgery is not known . We investigated this question in a r and omized trial . METHODS We conducted a multicenter , sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG ( with or without valve surgery ) with blood cardioplegia . After anesthesia induction and before surgical incision , patients were r and omly assigned to remote ischemic preconditioning ( four 5-minute inflations and deflations of a st and ard blood-pressure cuff on the upper arm ) or sham conditioning ( control group ) . Anesthetic management and perioperative care were not st and ardized . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , coronary revascularization , or stroke , assessed 12 months after r and omization . RESULTS We enrolled a total of 1612 patients ( 811 in the control group and 801 in the ischemic-preconditioning group ) at 30 cardiac surgery centers in the United Kingdom . There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group ( 212 patients [ 26.5 % ] and 225 patients [ 27.7 % ] , respectively ; hazard ratio with ischemic preconditioning , 0.95 ; 95 % confidence interval , 0.79 to 1.15 ; P=0.58 ) . Furthermore , there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury ( assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours ) , inotrope score ( calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery ) , acute kidney injury , duration of stay in the intensive care unit and hospital , distance on the 6-minute walk test , and quality of life . CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery . ( Funded by the Efficacy and Mechanism Evaluation Program [ a Medical Research Council and National Institute of Health Research partnership ] and the British Heart Foundation ; ERICCA Clinical Trials.gov number , NCT01247545 . ) BACKGROUND Remote ischemic preconditioning ( RIPC ) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery , but uncertainty about clinical outcomes remains . METHODS We conducted a prospect i ve , double-blind , multicenter , r and omized , controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol . The trial compared upper-limb RIPC with a sham intervention . The primary end point was a composite of death , myocardial infa rct ion , stroke , or acute renal failure up to the time of hospital discharge . Secondary end points included the occurrence of any individual component of the primary end point by day 90 . RESULTS A total of 1403 patients underwent r and omization . The full analysis set comprised 1385 patients ( 692 in the RIPC group and 693 in the sham-RIPC group ) . There was no significant between-group difference in the rate of the composite primary end point ( 99 patients [ 14.3 % ] in the RIPC group and 101 [ 14.6 % ] in the sham-RIPC group , P=0.89 ) or of any of the individual components : death ( 9 patients [ 1.3 % ] and 4 [ 0.6 % ] , respectively ; P=0.21 ) , myocardial infa rct ion ( 47 [ 6.8 % ] and 63 [ 9.1 % ] , P=0.12 ) , stroke ( 14 [ 2.0 % ] and 15 [ 2.2 % ] , P=0.79 ) , and acute renal failure ( 42 [ 6.1 % ] and 35 [ 5.1 % ] , P=0.45 ) . The results were similar in the per- protocol analysis . No treatment effect was found in any subgroup analysis . No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release , the duration of mechanical ventilation , the length of stay in the intensive care unit or the hospital , new onset of atrial fibrillation , and the incidence of postoperative delirium . No RIPC-related adverse events were observed . CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery . ( Funded by the German Research Foundation ; RIPHeart Clinical Trials.gov number , NCT01067703 . ) Background : Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion . In clinical studies , the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period . The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration . Methods : Elective coronary surgery patients were r and omly assigned to four different anesthetic protocol s ( n = 50 each ) . In a first group , patients received a propofol based intravenous regimen ( propofol group ) . In a second group , propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass ( SEVO pre group ) . In a third group , propofol was replaced by sevoflurane after completion of the coronary anastomoses ( SEVO post group ) . In a fourth group , propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation ( SEVO all group ) . Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively . Results : Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group . Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group . In the SEVO pre and SEVO post groups , stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group . Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group . Conclusion : In patients undergoing coronary artery surgery with cardiopulmonary bypass , the cardioprotective effects of sevoflurane were clinical ly most apparent when it was administered throughout the operation OBJECTIVE Minimally invasive mitral valve repair may be associated with prolonged cardioplegic arrest times and ischemic reperfusion injury . Intravenous ( propofol ) and volatile ( sevoflurane ) anesthesia are used routinely during cardiac surgery and are thought to provide cardioprotection ; however , the individual contribution of each regimen to cardioprotection is unknown . Therefore , the authors sought to compare the cardioprotective effects of propofol and sevoflurane anesthesia in patients undergoing minimally invasive mitral valve repair . DESIGN A single-center single-blind r and omized controlled trial . SETTING A specialized regional cardiac surgery center in Italy . PARTICIPANTS The study enrolled 62 adults undergoing elective isolated minimally invasive mitral valve repair for degenerative disease . Exclusion criteria included secondary mitral regurgitation , previously treated coronary artery disease , diabetes mellitus , chronic renal failure requiring dialysis , atrial fibrillation , and documented allergy to either propofol or sevoflurane . INTERVENTIONS All patients received video-assisted minimally invasive right minithoracotomy . Patients were r and omized to receive propofol or sevoflurane anesthesia in a 1:1 ratio . MEASUREMENTS AND MAIN RESULTS Cardiac troponin I release was measured over the first 72 hours postoperatively . Operative , cross-clamp , and total bypass times were similar between groups . Cardiac troponin I release was reduced nonsignificantly in the propofol group ( p = 0.62 ) , and peak troponin I release was correlated with cross-clamp time in both groups . There were no differences in terms of intraoperative lactate release and blood pH between groups . CONCLUSION Propofol and sevoflurane anesthesia were associated with similar degrees of myocardial injury , indicating comparable cardioprotection . Myocardial injury was related directly to the duration of cardioplegic arrest Background Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals . The present study investigated whether these effects were clinical ly relevant and would protect left ventricular ( LV ) function during coronary surgery . Methods Twenty coronary surgery patients were r and omly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane . Except for this , anesthetic and surgical management was the same in all patients . A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium . LV response to increased cardiac load , obtained by leg elevation , was assessed before and after cardiopulmonary bypass ( CPB ) . Effects on contraction were evaluated by analysis of changes in dP/dtmax . Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation ( R = slope of the relation between time constant & tgr ; of isovolumic relaxation and end-systolic pressure ) . Postoperative concentrations of cardiac troponin I were followed during 36 h. Results Before CPB , leg elevation slightly increased dP/dtmax in the sevoflurane group ( 5 ± 3 % ) , whereas it remained unchanged in the propofol group ( 1 ± 6 % ) . After CPB , leg elevation result ed in a decrease in dP/dtmax in the propofol group ( −5 ± 4 % ) , whereas the response in the sevoflurane group was comparable to the response before CPB ( 5 ± 4 % ) . Load dependence of LV pressure fall ( R ) was similar in both groups before CPB . After CPB , R was increased in the propofol group but not in the sevoflurane group . Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group . Conclusions Sevoflurane preserved LV function after CPB with less evidence of myocardial damage in the first 36 h postoperatively . These data suggest a cardioprotective effect of sevoflurane during coronary artery surgery OBJECTIVE The purpose of this study was to compare the effects of a total intravenous and a volatile anesthetic regimen on biochemical markers of hepatic and renal dysfunction after coronary artery surgery . DESIGN Prospect i ve , double-blind , r and omized clinical study . SETTING University hospital , single institutional . PARTICIPANTS Three hundred twenty patients undergoing elective coronary artery surgery were divided into 2 different anesthetic protocol s : propofol group ( n = 160 ) and sevoflurane group ( n = 160 ) . INTERVENTIONS Hemodynamic data were registered before the start of surgery , before the start of CPB , 15 minutes after the end of CPB , at arrival in the intensive care unit , and 6 and 12 hours after arrival in the intensive care unit . Serum glutamic oxaloacetic transaminase ( SGOT ) , serum glutamate pyruvate transaminase ( SGPT ) , serum lactate dehydrogenase ( LDH ) , and serum creatinine concentrations were measured before surgery , at arrival in the intensive care unit , and after 6 , 12 , 24 , and 48 hours . MEASUREMENTS AND MAIN RESULTS Postoperative levels of serum SGOT , SGPT , and LDH increased transiently in both anesthetic groups , but the increase was significantly lower in the sevoflurane group compared with the propofol group . Creatinine levels remained largely unchanged in both groups . CONCLUSION Postoperative biochemical markers of hepatic dysfunction were lower with a sevoflurane-based anesthetic regimen in patients undergoing coronary artery surgery with cardiopulmonary bypass Background and objectives : To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass , we performed a multicentre r and omized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans . Methods : We r and omly assigned 75 patients to propofol ( intravenous anaesthetic ) and 75 patients to desflurane ( volatile anaesthetic ) in addition to an opiate‐based anaesthesia for coronary artery bypass grafting . Peak postoperative troponin I release was measured as a marker of myocardial necrosis . Results : There was a significant ( P < 0.001 ) difference in the postoperative median ( 25th‐75th percentiles ) peak of troponin I in patients receiving propofol 5,5 ( 2,3‐9,5 ) ng dL−1 when compared to patients receiving desflurane 2,5 ( 1,1‐5,3 ) ng dL−1 . The median ( interquartile ) troponin I area under the curve analysis confirmed the results : 68 ( 30.5‐104.8 ) vs. 36.3 ( 17.9‐86.6 ) h ng dL−1 ( P = 0.002 ) . Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support ( 24/75 , 32.0 % vs. 31/75 , 41.3 % , P = 0.04 ) , and tends toward a reduction in number of Q‐wave myocardial infa rct ion , time on mechanical ventilation , intensive care unit and overall hospital stay . Conclusions : Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery BACKGROUND In experimental and clinical studies , volatile anaesthesia has proven to possess cardioprotective properties . However , no r and omized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available . We therefore compared isoflurane-sufentanil vs propofol-sufentanil anaesthesia in patients undergoing coronary artery bypass grafting . METHODS One hundred patients were r and omly assigned to receive isoflurane-sufentanil ( I ) ( n = 51 ) or propofol-sufentanil ( P ) ( n = 49 ) anaesthesia , aim ed at the same hypnotic depth . Postoperative concentrations of cardiac troponin I ( cTnI ) were followed for 72 h. Secondary outcome variables were length of stay ( LOS ) in the intensive care unit ( ICU ) and in hospital , and 30 day and 1 yr mortality and morbidity , defined as acute myocardial infa rct ion , arrhythmias , and cardiac dysfunction . Groups were compared by an on-treatment analysis , using linear mixed models for repeated measures . RESULTS Eighty-four patients completed the protocol ( I : 41 vs P : 43 ) . Postoperative cTnI concentrations increased to a maximum of I : 2.72 ng ml(-1 ) ( 1.78 - 5.85 ) and P : 2.64 ng ml(-1 ) ( 1.67 - 4.83 ) , but did not differ between groups ( P=0.11 ) . LOS in the ICU and in hospital was similar [ ICU I : 18 ( 17.0 - 21.5 ) vs P : 19 ( 17.0 - 22.0 ) h ; hospital I : 9 ( 6.5 - 8.0 ) vs P : 8 ( 6.0 - 9.0 ) days ] . Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups . One year after surgery , two patients had died of non-cardiac causes . No between-group differences in cardiac morbidity were found . CONCLUSIONS In this study , the use of isoflurane-sufentanil in comparison with propofol-sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels Background : Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge . We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients , as has been reported for animal ischemia models . Methods : In 17 university hospitals in France , Germany , Italy , and The Netherl and s , low-risk elective , on-pump coronary artery bypass graft surgery patients were r and omized to receive xenon , sevoflurane , or propofol-based total intravenous anesthesia for anesthesia maintenance . The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery . The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml . Secondary outcomes were the safety and feasibility of xenon anesthesia . Results : The first patient included at each center received xenon anesthesia for practical reasons . For all other patients , anesthesia maintenance was r and omized ( intention-to-treat : n = 492 ; per- protocol /without major protocol deviation : n = 446 ) . Median 24-h postoperative cardiac troponin I concentrations ( ng/ml [ interquartile range ] ) were 1.14 [ 0.76 to 2.10 ] with xenon , 1.30 [ 0.78 to 2.67 ] with sevoflurane , and 1.48 [ 0.94 to 2.78 ] with total intravenous anesthesia [ per- protocol ] ) . The mean difference in cardiac troponin I release between xenon and sevoflurane was −0.09 ng/ml ( 95 % CI , −0.30 to 0.11 ; per- protocol : P = 0.02 ) . Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia ( intention-to-treat : P = 0.05 ; per- protocol : P = 0.02 ) . Perioperative variables and postoperative outcomes were comparable across all groups , with no safety concerns . Conclusions : In postoperative cardiac troponin I release , xenon was noninferior to sevoflurane in low-risk , on-pump coronary artery bypass graft surgery patients . Only with xenon was cardiac troponin I release less than with total intravenous anesthesia . Xenon anesthesia appeared safe and feasible BACKGROUND This study was undertaken to compare the in vivo effects of isoflurane , sevoflurane , and propofol anesthesia on ischemia- and reperfusion-mediated free-radical injury and oxidative stress during coronary artery bypass graft surgery . We also compared the effects of these anesthetic agents on levels of end products of lipid peroxidation and nitric oxide ( NO ) in human right atrial tissue and blood . METHODS Sixty patients scheduled to undergo elective coronary surgery with cardiopulmonary bypass ( CPB ) were enrolled . Patients were r and omly allocated to receive 1 of 3 different anesthetic protocol s : propofol ( group A ) , isoflurane ( group B ) , or sevoflurane ( group C ) . We recorded global hemodynamic data ( mean arterial pressure , mean pulmonary artery pressure , central venous pressure , pulmonary capillary wedge pressure , cardiac output , cardiac index , and systemic vascular resistance index ) just before the start of surgery , before the start of CPB , 15 minutes after the end of CPB , at the end of the operation , 6 hours after installation in the intensive care unit , and 12 and 24 hours later . Sample s of the right atrial appendage were harvested before and after exposure of the heart to blood cardioplegia and short-term reperfusion under conditions of CPB . Biochemical and oxidative stress parameters were analyzed in both blood and tissue . RESULTS Hemodynamic parameters were kept stable throughout in all groups . Troponin I increased transiently with all used anesthetic regimens , but this increase was significantly lower in groups B and C. After clamp removal , lipid peroxidation in patients who received propofol ( group A ) was less than in patients who received isoflurane ( group B ) or sevoflurane ( group C ) ( P= .001 , P= .005 , respectively ) . Although the 3 groups showed no statistically significant differences in tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase , propofol significantly lowered NO production in atrial tissue after clamp removal and induced less NO production than sevoflurane ( P < .05 ) . CONCLUSION Inhalation anesthetics such as isoflurane and sevoflurane preserved cardiac function in coronary surgery patients after CPB with less evidence for myocardial damage than propofol . Furthermore , propofol induced lower blood levels of lipid peroxidation than isoflurane and sevoflurane . Propofol also increased glutathione peroxidase activity but induced less NO production compared to sevoflurane . These findings also support the cardioprotective properties that are demonstrated by hemodynamic parameters A r and omised study of 414 patients undergoing coronary artery surgery with cardiopulmonary bypass was conducted to compare the effects of a volatile anaesthetic regimen with either deesflurane or sevoflurane , and a total intravenous anaesthesia ( TIVA ) regimen on postoperative troponin T release . The primary outcome variable was postoperative troponin T release , secondary outcome variables were hospital length of stay and 1‐year mortality . Maximal postoperative troponin T values did not differ between groups ( TIVA : 0.30 [ 0.00–4.79 ] ng.ml−1 ( median [ range ] ) , sevoflurane : 0.33 [ 0.02–3.68 ] ng.ml−1 , and desflurane : 0.39 [ 0.08–3.74 ] ng.ml−1 ) . The independent predictors of hospital length of stay were the EuroSCORE ( p < 0.001 ) , female gender ( p = 0.042 ) and the group assignment ( p < 0.001 ) . The one‐year mortality was 12.3 % in the TIVA group , 3.3 % in the sevoflurane group , and 6.7 % in the desflurane group . The EuroSCORE ( p = 0.003 ) was the only significant independent predictor of 1‐year mortality Background Cardiac surgery is associated with some degree of myocardial injury . Preconditioning first described in 1986 was pharmacologic and non- pharmacologic . Among the long list of anesthetic drugs , isoflurane as an inhaling agent along with midazolam and propofol as injectable substances have been documented to confer some preconditioning effects on myocardium . Objectives In this study cardiac Troponin T ( cTnT ) , as a reliable marker , was used for evaluating myocardial injury . Methods This prospect i ve double blind study was comprised of 60 patients scheduled for CABG and were r and omly assigned into three groups who received infusion of propofol or midazolam or isoflorane . Surgical procedures and anesthetics were similar for 3 groups . cTnT measured preoperatively and at 12 , 24 and 36hr after arrival in ICU . Results There were no statistically significant differences in mean cTnT levels between three groups in the preoperative period and 12 - 24 hours after arrival in ICU . However , mean cTnT in 3 groups at 36 hours after arrival in ICU were different ( P < 0.013 ) and cTnT level was significantly higher in midazolam group ( P<0.001 ) and lowest in isoflurane group ( P=0.002 ) . Conclusion There were significant differences on cTnT levels between anesthetic groups of isofluran , midazolam and propofol at 36 hr after surgery . Preconditioning effect of isoflurane was higher than the other two groups BACKGROUND The effect of anaesthesia on postoperative outcome is unclear . Cardioprotective properties of volatile anaesthetics have been demonstrated experimentally and in haemodynamically stable patients undergoing coronary artery bypass grafting . Their effects in patients undergoing high-risk cardiac surgery have not been reported . METHODS We performed a multicentre , r and omized , parallel group , controlled study among patients undergoing high-risk cardiac surgery ( combined valvular and coronary surgery ) in 2008 - 2011 . One hundred subjects assigned to the treatment group received sevoflurane for anaesthesia maintenance , while 100 subjects assigned to the control group received propofol-based total i.v . anaesthesia . The primary outcome was a composite of death , prolonged intensive care unit ( ICU ) stay , or both . Thirty day and 1 yr follow-up , focused on mortality , was performed . RESULTS All 200 subjects completed the follow-up and were included in efficacy analyses , conducted according to the intention-to-treat principle . Death , prolonged ICU stay , or both occurred in 36 out of 100 subjects ( 36 % ) in the propofol group and in 41 out of 100 subjects ( 41 % ) in the sevoflurane group ; relative risk 1.14 , 95 % confidence interval 0.8 - 1.62 ; P=0.5 . No difference was identified in postoperative cardiac troponin release [ 1.1 ( 0.7 - 2 ) compared with 1.2 ( 0.6 - 2.4 ) ng ml(-1 ) , P=0.6 ] , 1 yr all-cause mortality [ 11/100 ( 11 % ) compared with 11/100 ( 11 % ) , P=0.9 ] , re-hospitalizations [ 20/89 ( 22.5 % ) compared with 11/89 ( 12.4 % ) , P=0.075 ] , and adverse cardiac events [ 10/89 ( 11.2 % ) compared with 9/89 ( 10.1 % ) , P=0.8 ] . CONCLUSIONS There was no observed beneficial effect of sevoflurane on the composite endpoint of prolonged ICU stay , mortality , or both in patients undergoing high-risk cardiac surgery . CLINICAL TRIAL REGISTRATION Clinical Trials.gov : identifier NCT00821262 . Eudra CT ( 2008 - 001752 - 43 ) Background This study aim ed to compare myocardial protective effects of anaesthesia with intravenous infusion of propofol versus inhalation of sevoflurane in patients undergoing heart valve replacement surgery with cardiopulmonary bypass . Methods Seventy-six patients undergoing valve replacement with cardiopulmonary bypass were r and omly assigned to propofol or sevoflurane anesthesia during the surgery , respectively . For assessing myocardial injury , cardiac troponin I ( cTnI ) and creatine kinase isozyme ( CK-MB ) were determined before induction ( T0 ) , 0.5 h ( T1 ) and 3 h ( T2 ) after aortic unclamping , and 24 h ( T3 ) and 48 h ( T4 ) after surgery . The concentrations of interleukin (IL)-6 and IL-10 as the systemic inflammatory and anti-inflammatory markers were also measured at above time points . Results In the sevoflurane group , the plasma concentrations of cTnI and CK-MB from Tl to T4 and the levels of IL-6 and IL-10 from T1 to T2 were lower than those in the propofol group . Moreover , a higher ratio of automatic heart beat recovery and a shorter length of intensive care unit or hospital stay were found in the sevoflurane group comparing with the propofol group . ConclusionS evoflurane anaesthesia produced more prominent myocardial protection and attenuated inflammatory response than propofol anaesthesia in patients with valve replacement surgery under cardiopulmonary bypass , result ing in shorter ICU and in-hospital stay . Retrospective clinical trial registration Identified as ChiCTR-IOR-16009979 at Background Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia . It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide , a biochemical marker for myocardial dysfunction . In addition , several variables associated with the protective effects of preconditioning were evaluated . Methods Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were r and omly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo ( oxygen – air mixture only ) or sevoflurane 4 vol% ( 2 minimum alveolar concentration ) . No other volatile anesthetics were administered at any time during the study . Treatment was strictly blinded to anesthesiologists , perfusionists , and surgeons . Biochemical markers of myocardial dysfunction and injury ( brain natriuretic peptide , creatine kinase – MB activity , and cardiac troponin T ) , and renal dysfunction ( cystatin C ) were determined . Results of Holter electrocardiography were recorded perioperatively . Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial sample s. Results Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide , a sensitive biochemical marker of myocardial contractile dysfunction . Pronounced protein kinase C & dgr ; and & egr ; translocation was observed in sevoflurane-preconditioned myocardium . In addition , postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients . No differences between groups were found for perioperative ST-segment changes , arrhythmias , or creatine kinase – MB and cardiac troponin T release . Conclusions Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest . This study demonstrated for the first time translocation of protein kinase C isoforms & dgr ; and & egr ; in human myocardium in response to sevoflurane We investigated if increasing propofol 's dosage to augment its antioxidant capacity during cardiopulmonary bypass ( CPB ) could confer cardiac protection . Fifty-four coronary artery bypass graft surgery patients were r and omly assigned to small-dose propofol ( Group P ; n = 18 ) , large-dose propofol ( Group HiP ; n = 18 ) , or isoflurane Group ( Group I ; n = 18 ) . After the induction , anesthesia was maintained with an inspired concentration of isoflurane 1%–3.5 % ( Group I ) or a continuous infusion of propofol 60 & mgr;g · kg−1 · min−1 ( Group P ) throughout the surgery . In Group HiP , this dose of propofol was increased to 120 & mgr;g · kg−1 · min−1 for 10 min before the onset of CPB until 15 min after aortic unclamping and then decreased to 60 & mgr;g · kg−1 · min−1 until the end of surgery . The duration of aortic cross-clamping was 83 ± 24 , 88 ± 22 , and 81 ± 20 min in Group P , Group HiP , and Group I , respectively ( P > 0.1 ) . Plasma malondialdehyde , a marker of oxidative stress , was significantly lower at 8 h after CPB , and Troponin I was lower at 24 h after CPB in Group HiP compared with Group P and Group I ( P < 0.05 ) . There was a significant reduction in inotropic requirements for separation from CPB in Group HiP compared with Group I. Postoperative systemic vascular resistance was significantly reduced in Group HiP as compared with Group I. Mean cardiac index was significantly higher at 24 h after CPB in Group HiP compared with Group P and Group I ( P < 0.05 ) ( Group I , 2.2 ± 0.1 ; Group P , 2.3 ± 0.2 ; and Group HiP , 2.8 ± 0.3 L · min−1 · m−2 , respectively ) . The duration of intensive care unit stay was significantly shorter in Group Hi-P compared with Group I. We conclude that administration of a large dose of propofol during CPB attenuates postoperative myocardial cellular damage as compared with isoflurane or small-dose propofol anesthesia The aim of the study was to evaluate the effects of sevoflurane and propofol on the activity of mitochondrial function related to ischemia-reperfusion injury , myocardial damage biomarkers release and clinical parameters in the postoperative period . Seventy-two patients scheduled for elective coronary artery bypass graft surgery with cardiopulmonary bypass were r and omized into two groups : 36 patients received sevoflurane during anesthesia ( Group S ) and 36 patients received propofol ( Group P ) . To investigate the functional activity of mitochondria , we used skinned fibers prepared from biopsies of right atrial tissue before cardioplegia and after the aorta cross-clamp removal ( within 10 - 15 minutes after reperfusion ) . Patients ’ clinical data ( length of stay in ICU , hemodynamic parameters , duration of mechanical ventilation ( MV ) and the amount of lactate and troponin I in the blood serum ) were evaluated postoperatively . The results showed that , before cardioplegia and after reperfusion , there was no significant difference in the mitochondrial routine and State 3 respiration rates between the groups . The effect of cytochrome c was higher in Group P. Troponin I concentration at the 12th hour after the surgery was 2.2 ± 0.8 ng/mL in Group S and 3.5 ± 1.1 ng/mL in Group P ( p<0.001 ) . There were no significant differences in the duration of mechanical ventilation , hemodynamic parameters and length of stay in the ICU between the groups . We conclude that sevoflurane slightly protects the mitochondrial outer membrane from ischemia-reperfusion injury and the loss of cytochrome c , yet has the similar effect on clinical parameters in the postoperative period when compared to propofol Myocardial ischemic damage is reduced by volatile anaesthetics in patients undergoing low‐risk coronary artery bypass graft surgery ; few and discordant results exist in other setting s. We therefore performed a r and omised controlled trial ( sevoflurane vs. propofol ) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery Objective : To evaluate the differences in extubation times in a group of cardiac surgical patients who were anesthetized and se date d with either IV propofol or inhaled volatile anesthetic agents . Design : This was a prospect i ve r and omized controlled trial performed between September 2009 and August 2011 . Setting : Cardiovascular ICU within a tertiary referral university-affiliated teaching hospital . Patients : One hundred forty-one patients undergoing coronary artery bypass graft surgery with normal or mildly reduced left ventricular systolic function . Intervention : Participants were r and omly assigned to receive anesthesia and postoperative sedation using IV propofol ( n = 74 ) or inhaled volatile ( isoflurane or sevoflurane ) anesthetic agent ( n = 67 ) . Measurements and Main Results : Patients se date d using inhaled volatile agent displayed faster readiness to extubation time at 135 minutes ( 95–200 min ) compared with those receiving IV propofol at 215 minutes ( 150–280 min ) ( p < 0.001 ) . Extubation times were faster within the volatile group at 182 minutes ( 140–255 min ) in comparison with propofol group at 291 minutes ( 210–420 min ) ( p < 0.001 ) . The volatile group showed a higher prevalence of vasodilatation with hypotension and higher cardiac outputs necessitating greater use of vasoconstrictors . There was no difference in postoperative pain scores , opioid consumption , sedation score , ICU or hospital length of stay , or patient mortality . Conclusions : Inhaled volatile anesthesia and sedation facilitates faster extubation times in comparison with IV propofol for patient undergoing coronary artery bypass graft surgery Background Renal impairment often follows cardiac surgery . The authors investigated whether sevoflurane produces greater increases in plasma creatinine concentration than isoflurane or propofol after elective coronary artery surgery . Methods As part of maintenance anesthesia , including during cardiopulmonary bypass , patients were r and omly allocated to receive one of three agents : isoflurane ( n = 118 ) , sevoflurane ( n = 118 ) , or propofol ( n = 118 ) . Fresh gas flows were 3 l/min . The preoperative plasma creatinine concentration was subtracted from the highest creatinine concentration in the first 3 postoperative days . A median maximum increase greater than 44 & mgr;m ( 0.5 mg/dl ) was regarded as clinical ly important . Data were analyzed on an intention-to-treat basis . Subgroup analyses were performed on per- protocol patients and those with preoperative renal impairment ( creatinine concentration > 130 & mgr;m [ 1.47 mg/dl ] or urea > 7.7 mm [ blood urea nitrogen , 21.6 mg/dl ] ) . Results The differences between the groups were small , clinical ly unimportant , and not statistically significant for the primary analysis and subgroups . The proportions of patients with creatinine increases greater than 44 & mgr;m were 15 % in the isoflurane group , 17 % in the sevoflurane group , and 11 % in the propofol group ( P = 0.45 ) . The median increases were 8 & mgr;m in the isoflurane group , 4 & mgr;m in the sevoflurane group , and 6 & mgr;m in the propofol group . The differences between the three median maximum increases were 1–4 & mgr;m ( P > 0.45 ) . In the subgroup with preoperative renal impairment , the median increases were 10 & mgr;m in the isoflurane group , 15 & mgr;m in the sevoflurane group , and 5 & mgr;m in the propofol group ( P = 0.72 ) . Conclusions Sevoflurane did not produce greater increases in creatinine than isoflurane or propofol after elective coronary artery surgery OBJECTIVE Several studies have suggested that the cardioprotective effects of halogenated anesthetics in cardiac surgery result in reduced cardiac biomarker release compared with total intravenous anesthesia ( TIVA ) . These findings came from relatively small r and omized clinical trials and meta-analyses . The authors of this study hypothesized that the beneficial effects of volatile anesthetics translate into a reduced length of hospital stay after coronary artery bypass grafting surgery ( CABG ) with cardiopulmonary bypass . DESIGN A r and omized controlled trial . SETTING Two university hospitals . PARTICIPANTS Adult patients undergoing elective CABG surgery with cardiopulmonary bypass . INTERVENTIONS Patients were assigned r and omly to 2 following groups : propofol-based TIVA group ( n = 431 ) and sevoflurane group ( n = 437 ) . MEASUREMENTS AND MAIN RESULTS The primary endpoint was hospital length of stay , and the secondary endpoint included postoperative troponin T and N-terminal pro-brain natriuretic peptide release and mortality . In the sevoflurane group , a reduced length of hospital stay was observed compared with the propofol-based TIVA group ( 10 [ 9 - 11 ] days v 14 [ 10 - 16 ] , p<0.001 ) as were reductions in cardiac troponin T release ( 0.18 ng/mL v 0.57 ng/mL at 24 hours , p<0.001 ) , in N-terminal pro-brain natriuretic peptide release ( 633 pg/mL v 878 pg/mL at 24 hours , p<0.001 ; 482 pg/mL v 1,036 pg/mL at 48 hours , p<0.001 ) , and in mortality at 1-year follow up ( 17.8 % v 24.8 % , p = 0.03 ) . CONCLUSIONS Anesthesia with sevoflurane reduced cardiac biomarker release and length of hospital stay after CABG with cardiopulmonary bypass surgery compared with propofol-based TIVA with a possible reduction in 1-year mortality Objective ( s ) : The aim of this study was to compare the effects of using inhalational anesthesia with desflurane with that of a total intravenous ( iv ) anesthetic technique using midazolam-fentanyl-propofol on the release of cardiac biomarkers after aortic valve replacement ( AVR ) for aortic stenosis ( AS ) . The specific objectives included ( a ) determination of the levels of ischemia-modified albumin ( IMA ) and cardiac troponin I ( cTnI ) as markers of myocardial injury , ( b ) effect on mortality , morbidity , duration of mechanical ventilation , length of Intensive Care Unit ( ICU ) and hospital stay , incidence of arrhythmias , pacing , cardioversion , urine output , and serum creatinine . Methodology and Design : Prospect i ve r and omized clinical study . Setting : Operation room of a cardiac surgery center of a tertiary teaching hospital . Participants : Seventy-six patients in New York Heart Association classification II to III presenting electively for AVR for severe symptomatic AS . Interventions : Patients included in the study were r and omized into two groups and subjected to either a desflurane-fentanyl based technique or total IV anesthesia ( TIVA ) . Blood sample s were drawn at preordained intervals to determine the levels of IMA , cTnI , and serum creatinine . Measurements and Main Results : The IMA and cTnI levels were not found to be significantly different between both the study groups . Patients in the desflurane group were found to had significantly lower ICU and hospital stays and duration of postoperative mechanical ventilation as compared to those in the TIVA group . There was no difference found in mean heart rate , urine output , serum creatinine , incidence of arrhythmias , need for cardioversion , and 30-day mortality between both groups . The patients in the TIVA group had higher mean arterial pressures on weaning off cardiopulmonary bypass as well as postoperatively in the ICU and recorded lower inotrope usage . Conclusion : The result of our study remains ambiguous regarding the overall protective effect of desflurane in patients undergoing AVR although some benefit in terms of shorter duration of postoperative mechanical ventilation , ICU and hospital stays , as well as cTnI , were seen . However , no difference in overall outcome could be clearly established between patients who received desflurane and those that were managed solely with IV anesthetic technique using propofol Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI ( ischaemia/reperfusion injury ) in patients undergoing CABG ( coronary artery bypass graft ) surgery . It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients . The present study investigated the efficacy of IsoPC ( isoflurane preconditioning ) , propofol treatment ( postconditioning ) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB ( cardiopulmonary bypass ) . Patients ( n = 120 ) selected for CABG surgery were r and omly assigned to one of four groups ( n = 30 each ) . After induction , anaesthesia was maintained either with fentanyl and midazolam ( control ; group C ) ; with propofol at 100 μg x kg(-1 ) of body weight x min(-1 ) before and during CPB followed by propofol at 60 μg x kg(-1 ) of body weight x min(-1 ) for 15 min after aortic declamping ( group P ) ; with isoflurane 1 - 1.5 % end tidal throughout the surgery ( group I ) or with isoflurane 1 - 1.5 % end tidal before CPB and switching to propofol at 100 μg x kg(-1 ) of body weight x min(-1 ) during CPB followed by propofol at 60 μg x kg(-1 ) of body weight x min(-1 ) for 15 min after aortic declamping ( group IP , i.e. IsoPC plus propofol postconditioning ) . A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI ( cardiac troponin I ) and CK-MB ( creatine kinase MB ) and f-FABP ( heart-type fatty acid-binding protein ) ( all P < 0.05 compared with control , group P or group I ) and facilitated postoperative myocardial functional recovery . During reperfusion , myocardial tissue eNOS ( endothelial NO synthase ) protein expression in group IP was significantly higher , whereas nitrotyrosine protein expression was lower than those in the control group . In conclusion , a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients Context Volatile anaesthetics may have direct cardioprotective properties due to effects similar to ischaemic preconditioning and postconditioning . Clinical results in cardiac surgery patients are controversial and may be related to the timing of administration of anaesthetics intraoperatively . Objective We hypothesised that the cardioprotective effect of sevoflurane in coronary bypass graft surgical patients would be greater if administration during anaesthesia continued in the ICU for at least 4 h postoperatively until weaning from mechanical ventilation . Design Double-blind , double-dummy , prospect i ve , r and omised and controlled clinical trial . Setting In a single centre between June 2006 and June 2007 . Patients Seventy-five adult patients were assigned r and omly to receive anaesthesia and postoperative sedation either with propofol ( control , n = 37 ) or sevoflurane ( n = 36 ) . Interventions Myocardial biomarkers were measured before surgery , at the time of admission to the intensive care unit and at 6 , 24 , 48 and 72 h. The need for inotropic support , and lengths of stay in the intensive care unit and hospital were also recorded . Main outcome measures Elevation of myocardial biomarkers was the primary endpoint . The secondary endpoints were haemodynamic events and lengths of stay in the intensive care unit and hospital . Results Necrosis biomarkers increased significantly in the postoperative period in both groups with no significant differences at any time . Inotropic support was needed in 72.7 and 54.3 % of patients in the propofol and sevoflurane groups , respectively ( P = 0.086 ) . There were no significant differences in haemodynamic variables , incidence of arrhythmias , myocardial ischaemia or and lengths of stay in the ICU and hospital between the two groups . Conclusion In patients undergoing coronary bypass graft surgery , continuous administration of sevoflurane as a sedative in the ICU for at least 4 h postoperatively did not yield significant improvements in the extent and time course of myocardial damage biomarkers compared to propofol Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally , but clinical evidence is lacking . Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass . One hundred and twelve patients who underwent valvular heart surgery were r and omized to receive either propofol or sevoflurane anesthesia , both with sufentanil . Using Acute Kidney Injury Network criteria , significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group ( 6 compared with 21 patients ) . The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group ( 5 compared with none ) . The postoperative cystatin C was significantly lower in the propofol group at 24 and 48 h. Serum interleukin-6 at 6 h after aorta cross-clamp removal , C-reactive protein at postoperative day 1 , and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group . Thus , propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane . This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators Background : Propofol ( 2,6-diisopropylphenol ) is an anesthetic drug with antioxidant and antiinflammatory properties , documented both in vitro and in experimental models of ischemia – reperfusion injury and septic shock . These properties have been related to the similarity of its chemical structure to that of endogenous tocopherols , which are phenol-containing radical scavengers . This study evaluated the effects of propofol on & agr;- and & ggr;-tocopherol ( & agr;- and & ggr;-T ) levels and on selected markers of oxidant – antioxidant and inflammatory status in patients undergoing cardiac surgery . Methods : Patients were r and omly assigned for anesthesia with either propofol ( propofol group , n = 22 ) or sevoflurane ( control group , n = 21 ) . Plasma levels of & agr;- and & ggr;-T , individual antioxidant capacity , malondialdehyde , and interleukin 10 were measured before , during , and after anesthesia . In addition , levels of the proinflammatory prostagl and in E2 as a marker of cyclooxygenase-2 activity and those of interleukin 10 were measured in whole blood cultured with bacterial lipopolysaccharide . Results : & ggr;-T levels increased significantly during surgery in propofol group ( P < 0.0001 vs. control group ) . By contrast , & agr;-T similarly decreased in both groups . Malondialdehyde and interleukin 10 increased markedly and individual antioxidant capacity decreased , without differences between groups . Prostagl and in E2 levels measured 24 h after anesthesia induction were significantly lower in the propofol than in the control group . In vitro studies highlighted the different capacity of & ggr;- and & agr;-T to impair prostagl and in E2 synthesis by human monocytes challenged with bacterial lipopolysaccharide . Conclusions : The antiinflammatory properties of propofol that may be linked to its effect on & ggr;-T levels could be relevant in controlling the inflammatory response that accompanies tissue injury during reperfusion BACKGROUND AND OBJECTIVE Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving pro-inflammatory cytokines such as tumour necrosis factor-alpha ( TNF-alpha ) , interleukin 6 ( IL-6 ) and interleukin 8 ( IL-8 ) . We investigated whether different anaesthetic techniques alter the pro-inflammatory cytokine response to cardiac surgery . METHODS Thirty patients scheduled for elective coronary artery bypass grafting ( CABG ) surgery were r and omized into three groups of 10 patients . They received either volatile inhalation induction and maintenance ( Group 1 ) or total intravenous anaesthesia with propofol and a minimal dose sufentanil ( Group 2 ) or a moderate dose midazolam-sufentanil ( Group 3 ) . The effect of the different anaesthetic techniques on plasma levels of TNF-alpha , IL-6 and IL-8 were examined during and after anaesthesia . RESULTS Concentrations of TNF-alpha , and IL-8 were comparable in the three groups throughout all measurements . Before the start of cardiopulmonary bypass , IL-6 was significantly higher in Group 1 than in Group 2 ( P = 0.009 ) or Group 3 ( P = 0.030 ) , but there were no differences between groups after cardiopulmonary bypass or postoperatively . In the three groups there was a positive correlation between aortic clamping time and serum concentrations of IL-6 ( r = 0.54 ) and IL-8 ( r = 0.62 ) . Length of stay in intensive care was correlated with high levels of TNF-alpha ( r = 0.78 ) . CONCLUSIONS Albeit there is difference between the volatile induction and maintenance of the anaesthesia method and the total intravenous anaesthesia technique on the pro-inflammatory cytokine response to surgical stimulation before starting of cardiopulmonary bypass , neither technique can modify the pro-inflammatory cytokine response to ischaemia-reperfusion or extracorporeal circulation To avoid intraoperative awareness and postoperative respiratory depression from high-dose opioid anesthesia , propofol ( P ) , or isoflurane ( I ) has been combined with moderate-dose opioid with varying results . However , the effects of both P and I on myocardial contractility and left ventricular afterload have not been completely quantified . The end-systolic pressure-diameter relationship ( ESPDR ) of the left ventricle ( LV ) is a reliable method to quantitatively assess LV contractility because it is relatively independent of changes in preload and incorporates afterload changes . The purpose of this study was to quantify the cardiodynamic effects of propofol-fentanyl ( PF ) anesthesia in comparison with isoflurane-fentanyl ( IF ) anesthesia in patients undergoing coronary artery bypass grafting ( CABG ) . Thirty patients with normal or moderately impaired LV function ( ejection fraction > or = 40 % with LV end-diastolic pressure < or = 18 mmHg , no preoperative akinesia or dyskinesia ) undergoing elective CABG were studied . After premedication with flunitrazepam , 2 mg orally , all patients were induced with thiopental , 1 mg/kg , fentanyl , 20 micrograms/kg , and vecuronium , 0.1 mg/kg , and were ventilated with oxygen/air ( F(1)O2 0.6 ) . Anesthesia was maintained throughout the procedure with a zero-order intravenous ( IV ) continuous infusion of P , 3 mg/kg/h ( PF group ) , or with isoflurane inhalation of 0.6 % ( IF group ) , supplemented by intermittent boluses ( 5 micrograms/kg ) of fentanyl ( up to a total maintenance dose of 30 micrograms/kg ) . After intubation , a cross-section of the LV was visualized by two-dimensional transesophageal echocardiography and an m-mode echocardiogram was obtained at the maximum anterior-posterior diameter . The radial artery pressure tracing and the ECG were simultaneously recorded with the M mode . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Volatile anesthetics protect the myocardium during coronary surgery . This study hypothesized that the use of a volatile agent in the anesthetic regimen would be associated with a shorter intensive care unit ( ICU ) and hospital length of stay ( LOS ) , compared with a total intravenous anesthetic regimen . Methods : Elective coronary surgery patients were r and omly assigned to receive propofol ( n = 80 ) , midazolam ( n = 80 ) , sevoflurane ( n = 80 ) , or desflurane ( n = 80 ) as part of a remifentanil-based anesthetic regimen . Multiple logistic regression analysis was used to identify the independent variables associated with a prolonged ICU LOS . Results : Patient characteristics were similar in all groups . ICU and hospital LOS were lower in the sevoflurane and desflurane groups ( P < 0.01 ) . The number of patients who needed a prolonged ICU stay ( > 48 h ) was also significantly lower ( propofol : n = 31 ; midazolam : n = 34 ; sevoflurane : n = 10 ; desflurane : n = 15 ; P < 0.01 ) . Occurrence of atrial fibrillation , a postoperative troponin I concentration greater than 4 ng/ml , and the need for prolonged inotropic support ( > 12 h ) were identified as the significant risk factors for prolonged ICU LOS . Postoperative troponin I concentrations and need for prolonged inotropic support were lower in the sevoflurane and desflurane group ( P < 0.01 ) . Postoperative cardiac function was also better preserved with the volatile anesthetics . The incidence of other postoperative complications was similar in all groups . Conclusions : The use of sevoflurane and desflurane result ed in a shorter ICU and hospital LOS . This seemed to be related to a better preservation of early postoperative myocardial function OBJECTIVES To determine if anesthesia with sevoflurane or target-controlled propofol reduced the time to tracheal extubation after coronary artery bypass graft surgery compared with isoflurane anesthesia . DESIGN A 3-arm ( isoflurane , sevoflurane , or propofol ) , r and omized , controlled trial with patients and intensive care staff blinded to the drug allocation . SETTING A single , tertiary referral hospital affiliated with the University of Melbourne . PARTICIPANTS Three hundred sixty elective coronary artery surgery patients . INTERVENTIONS Patients received either isoflurane ( control group , 0.5%-2 % end-tidal concentration ) , sevoflurane ( 1%-4 % end-tidal concentration ) , or target-controlled infusion of propofol ( 1 - 8 microg/mL plasma target concentration ) as part of a balanced , st and ardized anesthetic technique including 15 microg/kg of fentanyl . MEASUREMENTS AND MAIN RESULTS The primary outcome was time to tracheal extubation . The median time to tracheal extubation for the propofol group was 10.25 hours ( interquartile range [ IQR ] 8.08 - 12.75 ) , the sevoflurane group 9.17 hours ( IQR 6.25 - 11.25 ) , and the isoflurane group 7.67 hours ( IQR 6.25 - 9.42 ) . Intraoperatively , the propofol group required less vasopressor ( p = 0.002 ) and more vasodilator therapy ( nitroglycerin p = 0.01 , nitroprusside p = 0.002 ) . There was no difference among the groups in time to intensive care unit discharge . CONCLUSIONS The median time to tracheal extubation was significantly longer for the target-controlled propofol group . A significantly greater number in this group required the use of a vasodilator to control intraoperative hypertension OBJECTIVE To evaluate drug costs , time of mechanical ventilation , complications , and hospital length of stay comparing propofol-based with fentanyl-isoflurane-based anesthesia . DESIGN A prospect i ve , r and omized study . SETTING A university-affiliated , tertiary care community hospital . PARTICIPANTS Seventy patients undergoing primary coronary artery bypass surgery . INTERVENTIONS Patients were r and omized to either a low-dose fentanyl-isoflurane or a lower-dose fentanyl-isoflurane anesthetic supplemented with a continuous infusion of propofol . MEASUREMENTS AND MAIN RESULTS Fentanyl-isoflurane anesthesia was significantly less expensive ( $ 50.03+/-$27.26 v $ 121.69+/-$31.40 ) for anesthesia drugs and ( $ 58.08+/-$27.39 v $ 129.91+/-$31.52 ) for total drug costs . There was also a trend for patients in the fentanyl-isoflurane group to be extubated slightly sooner ( 388+/-202 v 449+/-252 min ) and go home sooner ( 5.1+/-1.8 v 6.0+/-3.0 days ) . CONCLUSION Fentanyl-isoflurane provides an inexpensive anesthetic that permits as prompt an extubation as propofol , thus conserving re sources for other patients BACKGROUND Whether remote ischaemic preconditioning , an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia , is beneficial for patients undergoing coronary artery bypass graft surgery is unknown . We did a single-blinded r and omised controlled study to establish whether remote ischaemic preconditioning reduces myocardial injury in these patients . METHODS 57 adult patients undergoing elective coronary artery bypass graft surgery were r and omly assigned to either a remote ischaemic preconditioning group ( n=27 ) or to a control group ( n=30 ) after induction of anaesthesia . Remote ischaemic preconditioning consisted of three 5-min cycles of right upper limb ischaemia , induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg , with an intervening 5 min of reperfusion during which the cuff was deflated . Serum troponin-T concentration was measured before surgery and at 6 , 12 , 24 , 48 , and 72 h after surgery . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00397163 . FINDINGS Remote ischaemic preconditioning significantly reduced overall serum troponin-T release at 6 , 12 , 24 , and 48 h after surgery . The total area under the curve was reduced by 43 % , from 36.12 microg/L ( SD 26.08 ) in the control group to 20.58 microg/L ( 9.58 ) in the remote ischaemic preconditioning group ( mean difference 15.55 [ SD 5.32 ] ; 95 % CI 4.88 - 26.21 ; p=0.005 ) . INTERPRETATION We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary centre could benefit from remote ischaemic preconditioning , using transient upper limb ischaemia Background / Aims : Study eluci date s and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis . Methods : Twenty-two patients were prospect ively r and omized in two groups regarding the anesthetic regime : sevoflurane and propofol . Hemodynamic parameters , biomarkers of cardiac injury and brain natriuretic peptide ( BNP ) were measured preoperatively and postoperatively . In tissue sample s , taken from the interventricular septum , key mitochondrial molecules were determined by Western blot , real time PCR , as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis . Results : The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group . Nevertheless , cytochrome c protein content was higher in propofol than sevoflurane receiving patients . Propofol group also showed higher protein level of connexin 43 ( Cx43 ) than sevoflurane group . Besides , immunogold analysis showed its mitochondrial localization . The mRNA level of mtDNA and uncoupling protein ( UCP2 ) were higher in propofol than sevoflurane patients , as well . On the other h and , there were no significant differences between groups in hemodynamic assessment , intensive care unit length of stay , troponin I and BNP level . Conclusions : Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms . It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase , while the effects of propofol occur through regulation of cytochrome c , Cx43 , mtDNA transcription and UCP2 In coronary surgery patients the use of a volatile anesthetic regimen with sevoflurane was associated with a better recovery of myocardial function and less postoperative release of troponin I. In the present study we investigated whether these cardioprotective properties were also apparent in the cardiac surgical setting of aortic valve replacement ( AVR ) surgery for the correction of aortic stenosis . Thirty AVR surgery patients were r and omly assigned to receive either target-controlled infusion of propofol or inhaled anesthesia with sevoflurane . Cardiac function was assessed perioperatively using a pulmonary artery catheter . Perioperatively , a high-fidelity pressure catheter was positioned in the left ventricle . Postoperative concentrations of cardiac troponin I were followed for 48 h. After cardiopulmonary bypass ( CPB ) , stroke volume and dP/dtmax were significantly higher in the patients with sevoflurane . Post-CPB , the effects of an increase in cardiac load on dP/dtmax were similar to pre-CPB in the sevoflurane group ( 1.0 % ± 5.4 % post-CPB versus 1.3 % ± 8.6 % pre-CPB ) but more depressed in the propofol group ( −8.2 % ± 4.4 % post-CPB versus 0.1 % ± 4.9 % pre-CPB ) . The rate of relaxation was significantly slower post-CPB in the propofol group . Postoperative levels of troponin I were significantly lower in the sevoflurane group . Our data indicate that the use of a volatile anesthetic regimen in AVR surgery was associated with better preservation of myocardial function and a reduced postoperative release of troponin High expression of cluster of differentiation (CD)39 and CD73 has cardio-protective effects . We hypothesised that the expression of CD39 and CD73 would differ between propofol- and volatile anaesthetic-based anaesthesia in patients undergoing open heart surgery ( OHS ) . The objective of this prospect i ve r and omized trial was to compare the changes in CD39 and CD73 levels in CD4 + T cells between propofol- and sevoflurane-based anaesthesia during OHS . The study r and omly allocated 156 patients undergoing OHS to a propofol or sevoflurane group . Blood was obtained preoperatively and up to 48 hours after weaning from cardiopulmonary bypass ( CPB ) . The expression levels of CD39 and CD73 in circulating CD4 + T cells , serum cytokines and other laboratory parameters were analysed . The primary outcome was the expression of CD39 and CD73 on CD4 + T cells . Demographic data and perioperative haemodynamic changes did not show significant differences between the two groups . The expression of CD39 and CD73 in the sevoflurane group was significantly lower than in the propofol group ( P < 0.001 ) . Other laboratory findings including cardiac enzymes and cytokine levels , did not show significant intergroup differences . Propofol attenuated the decrease in CD39 and CD73 in circulating CD4 + T cells compared to sevoflurane-based anaesthesia during OHS BACKGROUND Volatile ( inhaled ) anesthetic agents have cardioprotective effects , which might improve clinical outcomes in patients undergoing coronary‐artery bypass grafting ( CABG ) . METHODS We conducted a pragmatic , multicenter , single‐blind , controlled trial at 36 centers in 13 countries . Patients scheduled to undergo elective CABG were r and omly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic ( desflurane , isoflurane , or sevoflurane ) or to total intravenous anesthesia . The primary outcome was death from any cause at 1 year . RESULTS A total of 5400 patients were r and omly assigned : 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group . On‐pump CABG was performed in 64 % of patients , with a mean duration of cardiopulmonary bypass of 79 minutes . The two groups were similar with respect to demographic and clinical characteristics at baseline , the duration of cardiopulmonary bypass , and the number of grafts . At the time of the second interim analysis , the data and safety monitoring board advised that the trial should be stopped for futility . No significant difference between the groups with respect to deaths from any cause was seen at 1 year ( 2.8 % in the volatile anesthetics group and 3.0 % in the total intravenous anesthesia group ; relative risk , 0.94 ; 95 % confidence interval [ CI ] , 0.69 to 1.29 ; P=0.71 ) , with data available for 5353 patients ( 99.1 % ) , or at 30 days ( 1.4 % and 1.3 % , respectively ; relative risk , 1.11 ; 95 % CI , 0.70 to 1.76 ) , with data available for 5398 patients ( 99.9 % ) . There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events , including myocardial infa rct ion . CONCLUSIONS Among patients undergoing elective CABG , anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia . ( Funded by the Italian Ministry of Health ; MYRIAD Clinical Trials.gov number , NCT02105610 . We investigated the influence of either propofol or desflurane on the incidence of postoperative cognitive dysfunction in a r and omised trial of 180 patients undergoing coronary artery bypass surgery . The primary outcome was incidence of postoperative cognitive dysfunction at 3 months , defined as ≥ 1 SD deterioration in two or more of 12 neurocognitive tests . Secondary outcomes included early postoperative cognitive dysfunction ( between days three and seven ) , delirium on day one , morbidity and length of hospital stay . Early postoperative cognitive dysfunction was significantly higher with propofol compared with desflurane ( 56/84 ( 67.5 % ) vs 41/83 ( 49.4 % ) , respectively , p = 0.018 ) , but this effect was not seen at 3 months ( 10/87 ( 11.2 % ) vs 9/90 ( 10.0 % ) , respectively . There was no difference in delirium ( 7/89 ( 7.9 % ) vs 12/91 ( 13.2 % ) , respectively , length of hospital stay ( median ( IQR [ range ] ) 7 ( 6‐9 [ 4‐15 ] ) vs 6 ( 5‐7 [ 5‐16 ) days , respectively or other morbidities . Desflurane was associated with reduced early cognitive dysfunction |
11,243 | 32,308,706 | The meta- analysis revealed that Tai Chi could significantly improve global cognitive function ; memory and learning ; mental speed and attention ; ideas , abstract ion , figural creations , and mental flexibility ; and visuospatial perception .
The present review adds to the evidence showing that Tai Chi is potentially beneficial in improving cognitive functions among elderly people with MCI . | null | null |
11,244 | 11,687,054 | A dose response was seen for the main outcomes .
REVIEW ER 'S CONCLUSIONS Rizatriptan 5 mg and 10 mg are effective in treating acute migraine , with a dose-related increase in efficacy | BACKGROUND There are a number of different drug treatments for acute migraine , including currently four triptans , with several more likely to become available in the future .
There is a need for evidence -based information to help determine the balance of benefit and harm for acute migraine treatment .
OBJECTIVES To quantitatively assess the efficacy of a single dose of rizatriptan ( Maxalt ) for treating a single migraine attack using the outcomes of headache response and pain-free response at half-an-hour , one hour , two hours , and sustained relief over 24 hours .
To express efficacy in terms of numbers-needed-to-treat ( NNTs ) . | Rizatriptan is a potent , oral , 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan . It was postulated that this would result in more rapid onset of effect . This r and omized , double-blind , triple-dummy , parallel-groups study compared rizatriptan 5 mg , rizatriptan 10 mg , sumatriptan 100 mg , and placebo in 1268 out patients treating a single migraine attack . Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours , with significance at 1 hour ( 37 % versus 28 % , P = 0.010 ) . All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours ( P < or = 0.001 ) . The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that , after adjustment for age imbalance , rizatriptan 10 mg had earlier onset than sumatriptan 100 mg ( P = 0.032 ; hazard ratio 1.21 ) . Rizatriptan 10 mg was also superior to sumatriptan on pain-free response ( P = 0.032 ) , reduction in functional disability ( P = 0.015 ) , and relief of nausea at 2 hours ( P = 0.010 ) . Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg ( 33 % , P = 0.014 ) compared with sumatriptan 100 mg ( 41 % ) . We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg OBJECTIVE To evaluate the impact of sumatriptan succinate injection compared with placebo on productivity loss during a migraine attack in the workplace . DESIGN R and omized , double-blind , placebo-controlled , parallel-group clinical trial . SETTING Fifteen clinical centers in the United States . PATIENTS One hundred thirty-five patients 18 years and older diagnosed as having migraine according to International Headache Society criteria . INTERVENTIONS Patients self-administered sumatriptan injection ( 6 mg ) or matching placebo to treat a moderate or severe migraine occurring within the first 4 hours of a minimum 8-hour work shift . MAIN OUTCOME MEASURES Mean productivity loss 2 hours after dosing and across the work shift ; percentages of patients returning to normal work performance within 2 hours after dosing and across the work shift ; percentages of patients experiencing headache relief ( reduction of moderate or severe predose pain to mild or no pain ) 1 and 2 hours after dosing . RESULTS Mean productivity loss was significantly ( P < or = .002 ) lower in the sumatriptan group compared with the placebo group both during the 2-hour postdose period ( sumatriptan , 39 minutes ; placebo , 54 minutes ) and across the work shift ( sumatriptan , 86 minutes ; placebo , 168 minutes ) . Significantly ( P<.001 ) greater percentages of patients in the sumatriptan group compared with the placebo group returned to normal work performance by 2 hours after dosing ( sumatriptan , 52 % ; placebo , 9 % ) and across the work shift ( sumatriptan , 66 % ; placebo , 18 % ) . Significantly ( P < or = .001 ) greater percentages of patients in the sumatriptan group compared with the placebo group experienced headache relief 1 hour after dosing ( sumatriptan , 69 % ; placebo , 18 % ) and 2 hours after dosing ( sumatriptan , 79 % ; placebo , 32 % ) . CONCLUSION Sumatriptan reduced migraine-associated productivity loss during a minimum 8-hour work shift by approximately 50 % compared with placebo and alleviated headache in more than three fourths of patients Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract Rizatriptan wafer is a 5HT1B/1D agonist for use in the acute treatment of migraine . It is a freeze-fried formulation , approved for oral administration , which dissolves on the tongue and is swallowed with saliva . In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a r and omized , double-blind , placebo-controlled , out-patient study involving 39 migraineurs . Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo . At 1 h , 50 % of the patients receiving rizatriptan wafer and 50 % of the patients receiving placebo experienced significant relief . Implication s and potential reasons for a high placebo response are discussed We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials MK-462 is a potent , selective 5HT1D receptor agonist which may be useful in treating acute migraine . We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg ( n = 8) and 40 mg ( n = 36 ) vs placebo ( n = 21 ) , administered to 65 male and post-menopausal female migraine patients aged 22–51 with moderate or severe migraine headache . Headache severity and functional disability were measured at 0.5 , 1 , 1.5 , and 2 h post-dose . The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point . The 40 mg dose was well tolerated and was significantly ( p < 0.05 ) superior to placebo at the 1.5 and 2 h time points ( with 27/36 or 75 % obtaining relief at 2 h compared to 7/21 or 33 % for placebo ) . Adverse events occurred in 50 % of patients on 20 mg MK-462 , 72 % of those on 40 mg MK-462 , and in 52 % of placebo-treated subjects . The most common adverse events associated with MK-462 were drowsiness ( 20 mg 12 % ; 40 mg 44 % ; placebo 24 % ) , dry mouth ( 10 mg 36 % ; placebo 19 % ) , and lightheadedness/dizziness ( 40 mg 17 % ; placebo 10 % ) . Based on these preliminary results , MK-462 appears worthy of continued study for the treatment of acute migraine The efficacy and tolerability of rizatriptan ( MAXALT ™ ) and zolmitriptan ( ZOMIG ™ ) were compared in a r and omized , double – blind , double – dummy , stratified ( on prior use of rizatriptan and /or zolmitriptan ) , placebo – controlled , single attack study in 766 patients . Rizatriptan tended to provide freedom from pain sooner than zolmitriptan ( hazard ratio 1.26 , P = 0.075 ) , acting within 60 min following dosing . More patients were pain free at 2 h on rizatriptan than on zolmitriptan ( 43.2 % vs. 35.6 % , P = 0.041 ) , while headache relief at 2 h was similar ( 70.5 % vs. 66.8 % ) . At 2 h , fewer patients on rizatriptan had symptoms of photophobia ( 35.6 % vs. 43.5 % , P = 0.029 ) and nausea ( 25.2 % vs. 32.5 % , P = 0.046 ) , and more patients on rizatriptan had normal function ( 45.4 % vs. 37.0 % , P = 0.025 ) than zolmitriptan . Headache recurred in 28 % of patients taking rizatriptan , 29 % taking zolmitriptan and 26 % taking placebo . Both active treatments were effective compared to placebo and were well tolerated . The most common side – effects with rizatriptan were asthenia/fatigue , somnolence and dizziness , while the most common side – effects with zolmitriptan were asthenia/fatigue and dizziness Rizatriptan ( MAXALTTM , a registered trademark of Merck & Co. Inc. ) is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine . This r and omized , open-label , crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan ( IMIGRANTM , a registered trademark of GlaxoWellcome PLC ) 50-mg tablets in the treatment of a single migraine attack with each therapy . Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet ( 64.3 vs. 35.7 % , p ≤ 0.001 ) . Faster relief of headache pain was the most important reason for the preference , cited by 46.9 % of patients preferring rizatriptan and 43.4 % of patients who preferred sumatriptan . Headache relief at 2 h was 75.9 % with rizatriptan and 66.6 % with sumatriptan ( p ≤ 0.001 ) , with rizatriptan being superior to sumatriptan within 30 min of dosing . Fifty-five percent of patients were pain free 2 h after rizatriptan , compared with 42.1 % treated with sumatriptan ( p ≤ 0.001 ) , rizatriptan being superior within 1 h of treatment . Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication , compared to 32.3 % of patients on sumatriptan . Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea , phonophobia or photophobia , and patients with normal function 2 h after treatment intake ( p < 0.05 ) . More patients were ( completely , very or somewhat ) satisfied 2 h after treatment with rizatriptan ( 73.3 % ) than 2 h after treatment with sumatriptan ( 59.0 % ) ( p ≤ 0.001 ) . Additionally , 2 h after the dose , more patients found rizatriptan to be very convenient , convenient or somewhat convenient ( 87.2 % ) than they did sumatriptan ( 76.3 % ) ( p ≤ 0.001 ) . Both active treatments were well tolerated . The most common side effects with rizatriptan and sumatriptan were nausea ( 6.6 and 6.9 % of patients , respectively ) , dizziness ( 6.1 and 5.8 % ) and somnolence ( 7.4 and 6.7 % ) A vali date d migraine-specific question naire ( 24-h Migraine Quality of Life Question naire1 : 24-h MQoLQ ) was used to assess the impact of migraine and migraine therapy on health related quality of life during an acute migraine attack . Male and female migraineurs aged 18 - 55 years were r and omized to placebo ( n = 41 ) , rizatriptan 2.5 mg ( n = 47 ) , 5 mg ( n = 74 ) , or 10 mg ( n = 85 ) in a triple-blind , placebo-controlled clinical trial . Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability . After accounting , for multiple comparisons to placebo , rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ ( social functioning , migraine symptoms , and feelings/concerns ) . The O'Brien 's Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups ( p = 0.005 ) and for the overall close trend ( p 0.001 ) OBJECTIVE Compare adult migraineurs ' health related quality of life to adults in the general U.S. population reporting no chronic conditions , and to sample s of patients with other chronic conditions . METHODS Subjects ( n = 845 ) were surveyed 2 - 6 months after participation in a placebo-controlled clinical trial and asked to complete a question naire including the SF-36 Health Survey , a migraine severity measurement scale and demographics . Results were adjusted for severity of illness and comorbidities . Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions . RESULTS Response rate was 67 % . After adjustment for comorbid conditions , SF-36 scale scores were significantly ( P 0.001 ) lower in migraineurs , relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions . Some health dimensions were more affected by migraine than other chronic conditions , while other dimensions were less affected by migraine . Measures of bodily pain , role disability due to physical health and social functioning discriminated best between migraineurs , the U.S. sample , and patients with other chronic conditions . Patients reporting moderate , severe and very severe migraines scored significantly ( P < or = 0.001 ) lower on five of the eight SF-36 scales than the U.S. sample . CONCLUSIONS Migraine has a unique , significant quality of life burden OBJECTIVE To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet ( ODT ) 10-mg to sumatriptan 50-mg tablet . BACKGROUND Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation . Rizatriptan ODT is an orally disintegrating formulation of rizatriptan , a selective 5-HT1B/1D receptor agonist . This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine . METHODS This was a multicenter , r and omized , open-label , two-period crossover study conducted in the United States with 524 enrolled patients . Patients treated a single moderate or severe headache in each treatment period . Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet , then treated a second migraine with the alternate therapy . Patients completed diary assessment s at baseline , and 30 , 45 , 60 , 90 , and 120 minutes postdose and rated headache severity on a 4-point scale ( 0 = none , 1 = mild , 2 = moderate , and 3 = severe ) . At the final study visit following treatment of their second migraine , patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other . Safety measurements were recorded through st and ard adverse experience reporting . RESULTS Three hundred eighty-six patients treated two migraine attacks . For those patients who expressed a preference for either rizatriptan ODT or sumatriptan ( n = 374 ) , the percentage of patients who preferred rizatriptan ODT 10-mg ( 57 % , n = 213 ) was significantly greater than those who preferred sumatriptan 50-mg tablet ( 43 % , n = 161 ) ( P<.01 ) . For those patients who treated two migraine attacks and had drug severity measures for both attacks ( n = 384 ) , a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points ( 38 % versus 29 % and 58 % versus 49 % , respectively ) ( P<.01 ) . In addition , a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points ( 23 % versus 17 % [ P<.05 ] and 60 % versus 52 % [ P<.01 ] , respectively ) . Both rizatriptan ODT and sumatriptan were well tolerated . CONCLUSIONS A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine . Efficacy and safety data are consistent with the preference findings Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration . The efficacy and tolerability of oral rizatriptan ( 5 mg and 10 mg ) were examined in this multicenter , double-blind , outpatient study of 1473 migraineurs which featured r and omized , placebo-controlled treatment of migraine recurrences . On experiencing moderate or severe migraine headaches , patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing . Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg . At 2 hours postdose , the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg ( 62 % ) or 10 mg ( 71 % ) compared with placebo ( 35 % ) . Complete relief was also significantly higher after rizatriptan 5 mg ( 33 % ) and 10 mg ( 42 % ) compared with placebo ( 10 % ) . In patients experiencing headache recurrence after initial benefit , further relief was obtained in 71 % with rizatriptan 5 mg ( placebo 54 % ) and in 82 % with rizatriptan 10 mg ( placebo 44 % ) . Complete relief of recurrent headache was obtained in 36 % with rizatriptan 5 mg , 49 % with rizatriptan 10 mg , and 15 % with placebo ( P < 0.05 ) . The most common drug-related adverse experiences were dizziness , somnolence , asthenia/fatigue , and nausea ( the incidences of which were low and dose related ) . There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours . We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence , with the 10-mg dose preferred as it is more effective with a faster onset of action BACKGROUND Migraine headaches result in significant patient suffering and high costs to managed care organizations and employers . Studies that evaluate patient outcomes and the financial consequences of migraine treatment are important from a clinical and an economic perspective . METHODS This prospect i ve , observational study assessed the outcomes of migraineurs in a mixed model staff/ independent practice association managed care organization for patients previously diagnosed as having migraine who received their first prescription for sumatriptan . Data collected included medical as well as pharmacy cl aims and patient surveys to measure changes in satisfaction , health-related quality of life , workplace productivity , and nonworkplace activity after sumatriptan therapy was initiated . RESULTS A total of 178 patients completed the study . Results showed significant decreases in the mean number of migraine-related physician office visits , emergency department visits , and medical procedures in the 6 months after sumatriptan therapy compared with the 6 months before sumatriptan was used ( P<.05 ) . Four of the health-related quality -of-life dimensions and the physical component summary score measured by the SF-36 ( which is a valid , reliable general health status instrument ) showed significant improvements at 6 months compared with patients ' scores before use of sumatriptan ( P<.05 ) . Health-related quality of life measured by the disease-specific instrument MSQ ( Migraine-Specific Quality of Life Question naire-Version 1.0 , 1992 Glaxo Wellcome Inc , Research Triangle Park , NC ) showed significant improvement at 3 and at 6 months compared with baseline scores ( P<.05 ) . There were also improvements in patient satisfaction and significant reductions in time lost from workplace productivity and nonworkplace activity . CONCLUSION In the 6 months after sumatriptan therapy was initiated , health care re source use and time lost from workplace productivity and nonworkplace activity were reduced , while health-related quality of life and patient satisfaction scores improved for the managed care migraineurs enrolled in this study We present the first prevalence study of specific headache entities using the operational diagnostic criteria of the International Headache Society . One thous and 25 - 64 year old men and women , who lived in the western part of Copenhagen County were r and omly drawn from the Danish National Central Person Registry . All subjects were invited to a general health examination focusing on headache and including : a self-administered question naire concerning sociodemographic variables , a structured headache interview and a general physical and neurological examination . The participation rate was 76 % . Information about 79 % of the non- participants showed a slightly differing headache prevalence which was not quantitatively important . The following results in participants are therefore representative of the total sample . The lifetime prevalences of headache ( including anybody with any form of headache ) , migraine , and tension-type headache were 93 , 8 and 69 % in men ; and 99 , 25 and 88 % in women . The point prevalence of headache was 11 % in men and 22 % in women . Prevalence of migraine in the previous year was 6 % in men and 15 % in women and the corresponding prevalences of tension-type headache were 63 and 86 % . Differences according to sex were significant with a male : female ratio of 1:3 in migraine , and 4:5 in tension-type headache . The prevalence of tension-type headache decreased with increasing age , whereas migraine showed no correlation to age within the studied age interval . Headache disorders are extremely prevalent and represent a major health problem , which merits increased attention Objective : To examine the safety and efficacy of rizatriptan 10 mg PO in the treatment of multiple migraine attacks . Background : Rizatriptan is a potent and rapidly absorbed 5-HT1B/1D receptor agonist . Efficacy and general safety have been examined in controlled trials treating single migraine attacks . In the current placebo-controlled study , we report constancy of safety and efficacy of rizatriptan for patients treating four discrete migraine attacks . Methods : Patients with moderate or severe migraine ( n = 473 ) were r and omized to one of five sequence groups , in which each patient was to treat four migraine attacks . Patients in four groups received rizatriptan 10 mg for three of four attacks and placebo for the remaining attack . Patients in the fifth group received rizatriptan 10 mg for four attacks . Headache severity , functional disability , and migraine symptoms were measured immediately before dosing and at 0.5 , 1 , 1.5 , 2 , 3 , and 4 hours postdose . Results : After the first attack , response rates were 77 % for rizatriptan and 37 % for placebo ( p < 0.001 ) . Similar efficacy of rizatriptan , ranging from a 75 to 80 % response , was observed in each of the subsequent attacks with no evidence of tolerance to therapeutic effects . Most patients ( 93 % ) responded to rizatriptan 10 mg during the first or second attack . Adverse experiences were generally mild and transient , the most common being dizziness and somnolence . Incidence of adverse experiences per attack decreased after the first attack . Conclusions : Rizatriptan 10 mg PO is efficacious and generally well tolerated in acute migraine . Its efficacy is maintained throughout the treatment of multiple , discrete migraine attacks Rizatriptan ( MAXALTTM , Merck & Co. , Inc. ) is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine . This r and omized , double-masked , double-dummy , placebo-controlled study compared rizatriptan 10 mg to naratriptan ( NARAMIGTM , AMERGETM , both Glaxo Wellcome plc ) 2.5 mg in 522 patients treating a single migraine attack . Rizatriptan was more effective than naratriptan . Rizatriptan provided earlier headache relief than naratriptan ( hazard ratio 1.62 , p < 0.001 ) , acting as early as 30 min . More patients were pain free at 2 h on rizatriptan than on naratriptan ( 44.8 vs. 20.7 % , p < 0.001 ) . Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h ( 39.3 vs. 22.6 % , p < 0.001 ) . Both active treatments were effective compared to placebo . Both active treatments were well tolerated . The most common side effects with rizatriptan were dizziness , asthenia/fatigue , nausea and somnolence , while the most common side effects with naratriptan were dizziness and asthenia/fatigue & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine . This double-blind , placebo-controlled , crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg , and rizatriptan 10 mg versus sumatriptan 50 mg . A total of 1329 patients were allocated to one of five groups for treatment of two attacks : rizatriptan 5 mg/sumatriptan 25 mg ; sumatriptan 25 mg/rizatriptan 5 mg ; rizatriptan 10 mg/sumatriptan 50 mg ; sumatriptan 50 mg/rizatriptan 10 mg ; placebo/placebo . For each attack , patients rated headache severity , presence of associated symptoms , and functional disability prior to dosing and at intervals through 4 hours thereafter . Patients also rated their satisfaction with medication . Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan , respectively . The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication . All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing . All active treatments were well-tolerated and showed comparable safety profiles BACKGROUND Rizatriptan ( MK-462 ) is a new 5-hydroxytryptamine1D ( serotonin1D ; 5-HT1D ) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate . OBJECTIVE To assess the efficacy and tolerability of 10- , 20- , and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine . DESIGN R and omized , double-blind , parallel-group , placebo-controlled , outpatient trial . SETTING Ten US and 4 Dutch investigator centers . PATIENTS Patients who had migraine with or without aura ( N = 449 ) . MAIN OUTCOME MEASURE The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration ( ie , headache relief ) . RESULTS The proportion of patients with headache relief was 18 % for placebo ; 46 % for sumatriptan ; and 52 % for 10-mg , 56 % for 20-mg , and 67 % for 40-mg rizatriptan . All differences with placebo were statistically significant ( P < .001 ) , and 40-mg rizatriptan was superior to sumatriptan ( P = .01 ) . The proportion of patients who became free of pain at 2 hours was 3 % for the placebo-treated group ; 22 % for the sumatriptan-treated group ; and 26 % , 35 % , and 47 % for the group of patients who took the 10- , 20- , and 40-mg doses of rizatriptan , respectively ( all differences with placebo , P < .005 ; 40-mg rizatripan vs sumatriptan , P = .001 ) . The recurrence of headache within 24 hours was found to be equal across all treatment groups-approximately 40 % . Adverse events ( most commonly short-lasting mild or moderate dizziness and drowsiness ) occurred more frequently after a 40-mg dose of rizatriptan was given than after the other treatments . CONCLUSIONS The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo , and comparable with that of 100-mg sumatriptan succinate ; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate , although it was associated with a high frequency of adverse events Objective : To determine the within-patient consistency of response for rizatriptan , a 5-HT1B/1D receptor agonist for the acute treatment of migraine . Methods : Post hoc analysis was performed on data from a r and omized , double-blind , placebo-controlled clinical trial . Four hundred seventy-three patients with migraine diagnosed according to the criteria of the International Headache Society were r and omly assigned to one of five sequence groups in which each patient was scheduled to treat four separate moderate or severe migraine attacks . Patients in four groups received 10 mg of rizatriptan for three of four attacks and placebo for the remaining attack ; patients in the fifth group received 10 mg of rizatriptan for all four attacks . Headache severity , functional disability , and associated migraine symptoms were measured immediately before dosing and at regular intervals up to 4 hours after the dose . The analysis was based on efficacy at 2 hours after dosing , the last time point before escape medications were allowed . The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated . The analysis was descriptive , and no formal statistical testing was performed . Results : Of the evaluable patients who treated three migraine attacks with 10 mg of rizatriptan ( with an additional interspersed placebo-treated attack in most patients ) , 216 of 252 ( 86 % ) had pain relief ( reduction of pain to mild or none ) , 122 of 252 ( 48 % ) were pain free , 211 of 250 ( 84 % ) had no nausea , 163 of 251 ( 65 % ) had no photophobia , 182 of 252 ( 72 % ) had no phonophobia , 136 of 249 ( 55 % ) had no functional disability , and 233 of 252 ( 92 % ) had no need for escape medications at 2 hours after dosing in at least two of three attacks . Conclusion : The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures Rizatriptan ( MK-462 ) is a potent 5HTID receptor agonist . This multicenter , double-blind , placebo-controlled , outpatient study investigated the clinical elficacy , safety , and tolerability of rizatriptan ( 2.5 , 5 , and 10 mg ) as a function of dose for acute migraine . Fatients with moderate or severe migraine ( n=417 ) were treated with placebo ( n=67 ) , rizatriptan 2.5 mg ( n=75 ) , 5 mg ( n=130 ) , or rizatriptan 10 mg ( n=145 ) . Headache severity , functional disability , and migraine symptoms were measured immediately before dosing ( 0 ) and at 0.5 , 1 , 1.5 , 2 , 3 , and 4 h post-dose . Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe ( i.e placebo initiallyrizatriptan 10 mg as optional second dose ; rizatriptan 2.5 mg , 5 mg , or 10 mg initiallyplacebo as optional second dose ) . An upward dose-response relationship was observed among placebo rizatriptan 2.5 mg , 5 mg , and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief , i.e. , a change in headache severity to “ no pain or mild pain ” at 2 h post-dose . The relationship was evident even at the first recorded timepoint , 30 min , and was statistically significant at 1.5 h and beyond . At the primary timepoint of 2 h after the initial dose , the proportion of patients reporting pain relief was 47.6 % for rizatriptan 10 mg ; 45.4 % for rizatriptan 5 mg ; 21.3 % for rizatriptan 2.5 mg ; and 17.9 % for pacebo . Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2n post-dose . Rizatriptan 10 mg was consistently more effective than 5 mg , although the differences were not statistically significant . The most frequent clinical adverse events were dizziness , somnolence , and asthenia/fatigue . No patients were discontinued for any adverse experiences and there were no serious adverse experiences |
11,245 | 26,701,350 | Similarly , significant effects of history of periodontal disease were obtained for peri-implantitis for both implant and patient levels .
Furthermore , mean PIMT interval was demonstrated to influence the incidence of peri-implantitis at implant but not patient level .
PIMT interval showed significance at both levels .
Within the limitations of the present systematic review , it can be concluded that implant therapy must not be limited to the placement and restoration of dental implants but to the implementation of PIMT to potentially prevent biologic complications and hence to heighten the long-term success rate . | At the present time , peri-implantitis has become a global burden that occurs with a frequency from 1 % to 47 % at implant level .
Therefore , we aim ed herein at assessing the impact of peri-implant maintenance therapy ( PIMT ) on the prevention of peri-implant diseases . | OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review BACKGROUND The aim of this prospect i ve study is to evaluate the prevalence of mucositis , peri-implantitis , implant success , and survival in partially edentulous patients treated for generalized aggressive periodontitis ( GAgP ) and in periodontally healthy individuals . METHODS Thirty-five patients treated for GAgP and 18 periodontally healthy patients orally rehabilitated with osseointegrated implants participated in the study . They were first examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . Additional examinations were performed during a 3-month recall schedule over a 5- to 16-year period ( mean , 8.25 years ) . At every session , clinical parameters were recorded . At 1 , 3 , 5 , 10 , and 15 years after insertion of the superstructure , a microbiological and radiographic examination was performed . RESULTS The results show implant survival rates of 100 % in periodontally healthy individuals versus 96 % in GAgP patients . The implant success rate was 33 % in GAgP patients and 50 % in periodontally healthy individuals . In GAgP patients , mucositis was present in 56 % and peri-implantitis in 26 % of the implants . In periodontally healthy individuals , 40 % of the implants showed mucositis and 10 % peri-implantitis . GAgP patients had a five times greater risk of implant failure , a three times greater risk of mucositis , and a 14 times greater risk of peri-implantitis . CONCLUSION These results suggest that patients with treated GAgP are more susceptible to mucositis and peri-implantitis , with lower implant survival and success rates OBJECTIVE To monitor clinical , microbiological and host-derived alterations occurring around teeth and titanium implants during the development of experimental gingivitis/mucositis and their respective healing sequence in humans . MATERIAL AND METHODS Fifteen subjects with healthy or treated periodontal conditions and restored with dental implants underwent an experimental 3-week period of undisturbed plaque accumulation in the m and ible . Subsequently , a 3-week period with optimal plaque control was instituted . At Days 0 , 7 , 14 , 21 , 28 , 35 and 42 , the presence/absence of plaque deposits around teeth and implants was assessed , ( plaque index [ PlI ] ) and the gingival/mucosal conditions were evaluated ( gingival index[GI ] ) . Subgingival/submucosal plaque sample s and gingival/mucosal crevicular fluid ( CF ) sample s were collected from two pre-determined sites around each experimental unit . CF sample s were analyzed for matrix-metalloproteinase-8 ( MMP-8 ) and interleukin-1beta ( IL-1β ) . Microbial sample s were analyzed using DNA-DNA hybridization for 40 species . RESULTS During 3 weeks of plaque accumulation , the median PlI and GI increased significantly at implants and teeth . Implant sites yielded a greater increase in the median GI compared with tooth sites . Over the 6-week experimental period , the CF levels of MMP-8 were statistically significantly higher at implants compared with teeth ( P<0.05 ) . The CF IL-1β levels did not differ statistically significantly between teeth and implants ( P>0.05 ) . No differences in the total DNA counts between implant and tooth sites were found at any time points . No differences in the detection frequency were found for putative periodontal pathogens between implant and tooth sites . CONCLUSION Peri-implant soft tissues developed a stronger inflammatory response to experimental plaque accumulation when compared with that of their gingival counterparts . Experimental gingivitis and peri-implant mucositis were reversible at the biomarker level . Clinical ly , however , 3 weeks of resumed plaque control did not yield pre-experimental levels of gingival and peri-implant mucosal health indicating that longer healing periods are needed Dental implants have become an often used alternative to replace missing teeth , result ing in an increasing percentage of the adult population with implant supported prosthesis . Although favourable long-term results of implant therapy have been reported , infections occur . Until recently few reports included data on peri-implant infections , possibly underestimating this complication of implant treatment . It is possible that some infections around implants develop slowly and that with time peri-implantitis will be a common complication to implant therapy as an increasing number of patients have had their implants for a long time ( > 10 years ) . Data on treatment of peri-implant lesions are scarce leaving the clinician with limited guidance regarding choice of treatment . The aim of this thesis was to study the frequency of implant loss and presence of peri-implant lesions in a group of patients supplied with Brånemark implants 9 - 14 years ago , and to relate these events to patient and site specific characteristics . Moreover three surgical treatment modalities for peri-implantitis were evaluated . The thesis is based on six studies ; Studies I-III included 218 patients and 1057 implants followed for 9 - 14 years evaluating prevalence of , and factors related to implant loss ( Paper I ) and prevalence of peri-implant infections and related factors ( Paper I-III ) . Study IV is a review describing different treatment modalities of peri-implant infections . Study V is a prospect i ve cohort study involving 36 patients and 65 implants , evaluating the use of a bone substitute with or without the use of a resorbable membrane . Study VI is a case series with 12 patients and 16 implants , evaluating a bone substitute in combination with a resorbable membrane and submerged healing . This thesis demonstrated that : After 9 - 14 years the survival rates of dental implants are high ( 95.7 % ) . Implant loss seems to cluster within patients and are related to periodontitis evidence d as bone loss on radiographs at remaining teeth before implant placement . ( Paper I ) Peri-implantitis is a common clinical entity after 9 - 14 years . ( Paper II ) Using the implant as the statistical unit the level of keratinized mucosa and pus were explanatory for a bone level at > or =3 threads ( 1.8 mm ) . When the patient was used as a statistical unit a history of periodontitis and smoking were explanatory for peri-implantitis . ( Paper III ) Animal research has demonstrated that re-osseointegration can occur . The majority of human studies were found to be case reports . Using submerged healing and bone transplants , bone fill can occur in peri-implant defects . ( Paper IV ) Surgical treatment of peri-implantitis using a bone substitute with or without a resorbable membrane result ed in similar pocket depth reduction , attachment gain and defect fill . ( Paper V ) Bone substitute in combination with a resorbable membrane and a submerged healing result ed in defect fill > or = 2 threads ( 1.2 mm ) in 81 % of the implants . ( Paper VI ) In conclusion : 9 - 14 years after implant installation peri-implant lesions are a common clinical entity . Smokers and patients with a history of periodontal disease are at higher risk to develop peri-implantitis . Clinical improvements and defect fill can be obtained with various surgical techniques using a bone substitute AIM To determine the incidence of peri-implantitis in individuals with mucositis in a 5-year follow-up study . MATERIAL AND METHODS A sample of 212 partially edentulous individuals , rehabilitated with dental implants , underwent periodontal and peri-implant clinical examinations in 2005 ( baseline ) . Five years later , 80 individuals who had been diagnosed with mucositis in the baseline examination were re-examined . These individuals were divided into two groups : one group with preventive maintenance during the study period ( GTP ; n = 39 ) , and another group without preventive maintenance ( GNTP ; n = 41 ) . The following parameters were clinical ly evaluated : plaque index , bleeding on periodontal and peri-implant probing , periodontal and peri-implant probing depth , suppuration and peri-implant bone loss . The influence of biological and behavioural risk variables associated with the occurrence of peri-implantitis was analysed using univariate and multivariate logistic regression analyses . RESULTS The incidence of peri-implantitis in the global sample was 31.2 % ( GNTP = 43.9 % and GTP = 18.0 % ) . CONCLUSION The absence of preventive maintenance in individuals with pre-existing peri-implant mucositis was associated with a high incidence of peri-implantitis . Clinical parameters , such as bleeding on peri-implant probing , periodontal probing depth and the presence of periodontitis were associated with a higher risk of developing peri-implantitis AIM The aim of the present study was to analyze tissue reactions to plaque formation following ligature removal at commercially available implants exposed to experimental peri-implantitis . MATERIAL AND METHODS Six Labrador dogs about 1 year old were used . All m and ibular premolars and the three anterior premolars in both sides of the maxilla were extracted . After 3 months four implants representing four different implant systems with different surface characteristics -- implant group A ( turned ) , B ( TiOblast ) , C ( s and blasted acid-etched ; SLA ) and D (TiUnite)--were placed in a r and omized order in the right side of the m and ible . Three months after implant installation experimental peri-implantitis was initiated by placement of ligatures in a submarginal position and plaque accumulation . At week 12 , when about 40 - 50 % of the supporting bone was lost , the ligatures were removed . During the subsequent 24-week period plaque accumulation continued . Radiographic and clinical examinations were performed during the ' active breakdown ' period ( plaque accumulation and ligatures ) and the plaque accumulation period after ligature removal . The experiment was terminated at week 36 . RESULTS The bone loss that took place during the ' active breakdown ' period varied between 3.5 and 4.6 mm . The additional bone loss that occurred during the plaque accumulation period after ligature removal was 1.84 ( A ) , 1.72 ( B ) , 1.55 ( C ) and 2.78 mm ( D ) . CONCLUSION Spontaneous progression of experimentally induced peri-implantitis occurred at implants with different geometry and surface characteristics . Progression was most pronounced at implants of type D ( TiUnite surface ) A clinical trial was performed to study the result of periodontal treatment following different modes of periodontal surgery in patients not recalled for maintenance care . The material consisted of 25 patients distributed into 5 groups . Following an initial examination , all patients underwent presurgical treatment including case presentation and instruction in oral hygiene measures . This instruction was given once . The various patient groups were then subjected to one of the following surgical procedures : 1 ) the apically repositioned flap operation including elimination of bony defects 2 ) the apically repositioned flap operation including curettage of bony defects but without removal of bone 3 ) the " Widman flap " technique including elimination of bony defects 4 ) the " Widman flap " technique including curettage of bony defects but without removal of bone 5 ) gingivectomy including curettage of bony defects but without removal of bone . Six , 12 and 24 months after completion of the treatment , the patients were recalled for assessment of their oral hygiene st and ard and periodontal conditions . The results showed that case presentation and oral hygiene instruction given once , only temporarily improved the patient 's oral hygiene habits . Renewed accumulation of plaque in the operated areas result ed in recurrence of periodontal disease including a significant further loss of attachment . All five different techniques for surgical pocket elimination were equally ineffective in preventing recurrence of destructive periodontitis AIM The aim of this 10-year study ( observation time 8 - 12 years , mean : 10 years ) was to compare the survival rates , success rates and incidences of biological complications using three different implant design s of the ITI Dental Implant System . MATERIAL AND METHODS In 89 dental patients treated comprehensively , a total of 112 hollow screw ( HS ) , 49 hollow cylinder ( HC ) and 18 angulated hollow cylinder ( AHC ) implants were installed depending on the available bone volume and according to prosthetic needs . One and 10 years after surgical placement , clinical and radiographic parameters were assessed . The incidences of peri-implantitis according to various thresholds were registered over 10 years of maintenance . RESULTS Success criteria at 10 years were set at : pocket probing depth ( PPD ) < or = 5 mm , bleeding on probing (BoP)- , bone loss < 0.2 mm annually . The survival rate for HS was 95.4 % , for HC 85.7 % and for AHC 91.7 % . Ninety percent of all the HS , 71 % of the HC and 88 % of the AHC did not present with an incidence of peri-implantitis over the 10 years , HC having significantly higher incidence of peri-implantitis than HS ( P < 0.004 ) . With the success criteria set above , a success rate for HS of 74 % , for HC of 63 % and for AHC of 61 % was identified at 10 years . However , including a definition of PPD < or = 6 mm , BoP - and bone loss < 0.2 mm annually for success , the rates for HS were 78 % , for HC 65 % and for AHC 67 % , respectively . Basing success criteria purely on clinical parameters ( without radiographic analysis ) , such as : PPD < or = 5 mm and BoP- , the success rates increased to 90 % , 76 % and 89 % , respectively . With PPD < or = 6 mm and BoP - as success criteria chosen , the respective rates were 94 % , 82 % and 94 % for HS , HC and AHC implants , respectively . CONCLUSIONS A significantly higher survival rate as well as a significantly lower incidence of peri-implantitis was identified for hollow screw design ITI Dental Implants after 10 years of service when compared to hollow cylinder design ITI Dental Implants ( 95.4 % vs. 85.7 % ; 10 % vs. 29 % ) . Depending on the setting of the threshold criteria for success , success rates are highly variable and hence , reporting of success rates with elaboration on the criteria set appears crucial for comparison of different studies BACKGROUND The biofilm that forms and remains on tooth surfaces is the main etiological factor in caries and periodontal disease . Prevention of caries and periodontal disease must be based on means that counteract this bacterial plaque . OBJECTIVE To monitor the incidence of tooth loss , caries and attachment loss during a 30-year period in a group of adults who maintained a carefully managed plaque control program . In addition , a comparison was made regarding the oral health status of individuals who , in 1972 and 2002 , were 51 - 65 years old . MATERIAL AND METHODS In 1971 and 1972 , more than 550 subjects were recruited . Three hundred and seventy-five subjects formed a test group and 180 a control group . After 6 years of monitoring , the control group was discontinued but the participants in the test group was maintained in the preventive program and was finally re-examined after 30 years . The following variables were studied at Baseline and after 3 , 6 , 15 and 30 years : plaque , caries , probing pocket depth , probing attachment level and CPITN . Each patient was given a detailed case presentation and education in self-diagnosis . Once every 2 months during the first 2 years , once every 3 - 12 months during years 3 - 30 , the participants received , on an individual need basis , additional education in self-diagnosis and self-care focused on proper plaque control measures , including the use of toothbrushes and interdental cleaning devices ( brush , dental tape , toothpick ) . The prophylactic sessions that were h and led by a dental hygienist also included ( i ) plaque disclosure and ( ii ) professional mechanical tooth cleaning including the use of a fluoride-containing dentifrice/paste . RESULTS Few teeth were lost during the 30 years of maintenance ; 0.4 - 1.8 in different age cohorts . The main reason for tooth loss was root fracture ; only 21 teeth were lost because of progressive periodontitis or caries . The mean number of new caries lesions was 1.2 , 1.7 and 2.1 in the three groups . About 80 % of the lesions were classified as recurrent caries . Most sites , buccal sites being the exception , exhibited no sign of attachment loss . Further , on approximal surfaces there was some gain of attachment between 1972 and 2002 in all age groups . CONCLUSION The present study reported on the 30-year outcome of preventive dental treatment in a group of carefully monitored subjects who on a regular basis were encouraged , but also enjoyed and recognized the benefit of , maintaining a high st and ard of oral hygiene . The incidence of caries and periodontal disease as well as tooth mortality in this subject sample was very small . Since all preventive and treatment efforts during the 30 years were delivered in one private dental office , caution must be exercised when comparisons are made with longitudinal studies that present oral disease data from r and omly selected subject sample A clinical trial was undertaken to study the healing capacity of the periodontal tissues following different modes of periodontal surgery in patients whose oral hygiene was professionally maintained at an optimal level . Fifty patients , distributed into five groups , participated in the study . Following an initial examination and presurgical treatment , the various patient groups were subjected to one of the following surgical procedures : 1 ) the apically repositioned flap operation including elimination of bony defects , 2 ) the apically repositioned flap operation including curettage of the bony defects but without removal of bone , 3 ) the " Widman flap " technique including elimination of bony defects , 4 ) the " Widman flap " technique including curettage of the bony defects but without removal of bone , 5 ) gingivectomy including curettage of the bony defects but without removal of bone . After surgery , all patients received oral hygiene instruction and professional cleaning of the teeth once every 2 weeks during a 2-year period . The results showed that periodontal disease can be cured and further destruction of the periodontal tissues avoided irrespective of the surgical technique utilized for pocket elimination . Different surgical techniques , however , promoted varying degrees of regeneration of the supporting tissues . The most favourable healing was obtained when resection of bone was avoided and when complete coverage of the alveolar bone was ensured 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 |
11,246 | 14,640,376 | Finally , pooled analysis did not find a significant association between testosterone and pregnancy rate .
In conclusion , the best available evidence , though limited , suggests that the most clinical ly useful predictors of gonadotrophin ovulation induction outcome in normogonadotrophic women are obesity and insulin resistance | A systematic review was conducted to determine whether initial screening characteristics of women with normogonadotrophic anovulatory infertility predict clinical ly significant outcomes of ovulation induction with gonadotrophins , and to obtain pooled estimates of their predictive value through meta- analysis . | OBJECTIVE To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins . DESIGN Retrospective data analysis of two prospect i ve , r and omized , multicenter studies . SETTING Clinical development unit of biotechnology company . PATIENT(S ) Four hundred sixty-five World Health Organization II anovulatory patients undergoing ovulation induction . MAIN OUTCOME MEASURE(S ) Ovarian response to stimulation , ovulation ( mid-luteal serum progesterone > 30 nmol/L ) , cancellation rate , pregnancy rate , and incidence of the ovarian hyperstimulation syndrome ( OHSS ) according to baseline ovarian volume ( day 2 - 5 ) before stimulation . RESULT ( S ) Mean ovarian volume was 11.55 + /- 6.0 cm(3 ) ( range , 0.8 - 49.3 cm(3 ) ) . Small ovarian volume was associated with lower rates of cycle cancellation owing to risk for OHSS ( 3 vs. 29 patients [ 2.8 % vs. 9 % ] ) . Patients with small ovarian volume ( < 7.25 cm(3 ) ) required fewer ampules of FSH ( 1373 IU vs. 1629 IU ) and shorter duration of stimulation ( 16 vs. 18.1 days ) and had higher ovulation rate than did patients with mid-range and larger ovarian volume ( 84.3 % vs. 69.1 % and 68.8 % , respectively ) . The clinical pregnancy rate per cycle of hCG administration was similar in the three groups ( 25.8 % , 28.1 % , and 27.5 % ) . CONCLUSIONS World Health Organization II anovulatory women with medium-sized or large ovaries who are undergoing low-dose gonadotropin stimulation for ovulation induction may have higher risk for OHSS than do women with small ovaries . Women with small ovaries who meet criteria for administration of hCG respond better to ovulation induction and have a similar likelihood of conceiving compared with women with larger ovaries We previously tested a combined regimen based on the administration of gonadotropin in the early follicular phase followed by pulsatile gonadotropin-releasing hormone ( GnRH ) until complete follicular maturation in patients suffering from polycystic ovarian disease . Despite good clinical results , a high rate of premature luteinization was observed with this approach . We therefore evaluated in this study whether starting pulsatile GnRH therapy before gonadotropin administration might reduce premature luteinization . Eight women underwent induction of ovulation with both combined therapy and pure exogenous follicle-stimulating hormone alone using a crossover scheme . No premature luteinization and a single follicular growth were recorded with the modified combined regimen . Clinical results ( 8/8 versus 3/7 ovulatory cycles ; 3/8 versus 1/7 pregnancies ) favor the combined approach over gonadotropin alone A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospect i ve r and omized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women . The objectives was to assess potential differences in duration of treatment , ovarian stimulation ( serum FSH levels ) , and response [ serum estradiol ( E2 ) levels and number and size of follicles ] . Monitoring ( blood sampling and transvaginal sonography ) took place on the day of initiation of treatment , the first day of ovarian response as assessed by ultrasound ( i.e. the first day a follicle > or = 10 mm could be recognized ) , the day of hCG administration to induce ovulation , and 3 days thereafter . The median duration of treatment in the low dose step-up group was 18 ( range , 7 - 41 ) days compared to 9 ( range , 4 - 16 ) days in the step-down group ( P = 0.003 ) , and the total numbers of ampules administered were 20 ( range , 7 - 69 ) and 14 ( range , 7 - 33 ) , respectively ( P = NS ) . Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant ( median increase , 2%/day ) in patients receiving the low dose step-up protocol , but showed a decrease ( median , 5%/day ) in step-down cycles ( P < 0.001 ) . Monofollicular growth , defined as not more than one follicle 16 mm or larger on the day of hCG administration , was observed in 56 % of low dose step-up and 88 % of step-down cycles ( P = 0.04 ) . The percentage of patients with normal range periovulatory E2 serum levels ( 500 - 1500 pmol/L ) was 33 % in the low dose step-up group vs. 71 % in the step-down group ( P = 0.03 ) . We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological , late follicular phase FSH serum profile than a low dose step-up protocol . This results in a shorter duration of treatment , a greater number of monofollicular cycles , and more cycles with periovulatory E2 levels within the normal range in the step-down protocol BACKGROUND This study revisited the ultrasonographic diagnostic criteria of polycystic ovary syndrome ( PCOS ) and studied the relationship between the major hormonal and metabolic features of PCOS and the follicle number per ovary ( FNPO ) . METHODS This prospect i ve study included 214 women with PCOS compared with 112 women with normal ovaries . Main clinical , biological and ultrasonographic markers of PCOS were assessed during the early follicular phase . RESULTS The mean FNPO of follicles 2 - 5 mm in size was significantly higher in polycystic ovaries than in controls , while it was similar within the 6 - 9 mm range . Setting the threshold at 12 for the 2 - 9 mm FNPO offered the best compromise between specificity ( 99 % ) and sensitivity ( 75 % ) . Within the 2 - 5 mm follicular range , we found significant positive relationships between the FNPO and and rogens . The FNPO within the 6 - 9 mm range was significantly and negatively related to body mass index and fasting insulin serum level . CONCLUSIONS We propose to modify the definition of polycystic ovaries by adding the presence of > or = 12 follicles measuring 2 - 9 mm in diameter ( mean of both ovaries ) . Also , our findings strengthen the hypothesis that the intra-ovarian hyper and rogenism promotes excessive early follicular growth and that further progression can not proceed normally because of hyperinsulinism and /or other metabolic influence linked to obesity In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome ( PCOS ) , a prospect i ve study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction . Baseline evaluation of serum concentrations of luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , testosterone , fasting insulin , insulin-like growth factor-1 ( IGF-1 ) , IGF binding protein-1 ( IGFBP-1 ) and sex hormone-binding globulin ( SHBG ) were performed before administering gonadotrophin-releasing hormone agonist ( GnRHa ) . Two weeks later , human menopausal gonadotrophin ( HMG ) was given in a st and ard individualized protocol according to ovarian response , until human chorionic gonadotrophin ( HCG ) was given . Serum concentrations of insulin , IGF-1 , and IGFBP-1 were unaffected by GnRHa . The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated . The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women . No correlation was observed between HMG requirements and IGF-1 or other hormones . Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG . Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI . We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which , when high , induce , hypothetically , a hyper and rogenic intrafollicular milieu In 20 patients with clinical ly , sonographically and endocrinologically proven polycystic ovary syndrome , ovulation induction with low doses of follicle stimulating hormone ( FSH ) was attempted by administration for 27 menstrual cycles . One ampule FSH was administered from day 3 onwards . If the ovarian response was inadequate after days 10 - 12 , the daily FSH dose was increased by half an ampule until ovulation induction . Of the cycles , 55.5 % were monofollicular , whereas 4 cycles had to be cancelled due to a multifollicular response or failure of ovarian stimulation . On average , 14.4 ampules was used , and human chorionic gonadotropin was given on day 16 . Seven pregnancies were established , with all of them ongoing at this writing . One twin pregnancy and one triplet pregnancy occurred . Even in polycystic ovary syndrome patients , low-dose administration of FSH allows safe stimulation , with a low incidence of ovarian hyperstimulation , a high pregnancy rate and an acceptably low risk of multiple pregnancies OBJECTIVE To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant , normogonadotropic , chronic anovulation . DESIGN Prospect i ve , r and omized trial . SETTING University-based infertility clinic . PATIENT(S ) Fifty-one women . INTERVENTION(S ) Subjects were r and omized to receive either urinary FSH ( 35 patients , 64 cycles ) or recombinant FSH ( 16 patients , 32 cycles ) . A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken . MAIN OUTCOME MEASURE(S ) Cumulative ovulation and pregnancy rates after three cycles , total gonadotropin dose , duration of stimulation , and single follicle development rate . RESULT ( S ) Cumulative ovulation rates were 89.3 % and 93.1 % for the urinary FSH and recombinant FSH groups , respectively . The threshold and total doses of FSH and the duration of stimulation were similar between the two groups . Significantly more single follicle development was noted in the recombinant FSH group . The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2 % and 27.6 % . There were three sets of twins in the urinary FSH group . No case of ovarian hyperstimulation syndrome was encountered . CONCLUSION ( S ) Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol Abstract Purpose : Our goal was to investigate the safety , effectiveness , and feasibility for the practicing physician of stepwise and low-dose administration of FSH in WHO group II anovulatory infertile women . Methods : Infertile female patients ( n=234 ) suffering from WHO group II anovulation , and who failed to became pregnant with clomiphene citrate , were included in a multicenter , prospect i ve , clinical study of treatment with a protocol of chronic low-dose and small incremental rises with urinary purified or highly purified FSH . Follicular development was monitored with ultrasonographic scans . Results : The 234 patients received a total of 534 cycles of treatment , for a mean number of 2.3 treated cycles per patient . hCG was withheld in 65 ( 12.2 % ) cyles because of no response and in 28 ( 5.2 % ) cycles because of hyperresponse . Of the remaining 441 cycles , 419 ( 95 % ) were ovulatory , and in 198 ( 47.3 % ) of these cycles a single dominant follicle developed . There were 93 pregnancies ( 39.7 % per patient ) , for a cycle fecundity rate of 17.4 % . Cumulative conception rate after two treated cycles was 33.5 % . There were 14 ( 15 % ) pairs of twins and 10 ( 10.8 % ) spontaneous miscarriages . The prevalence of complications was low with no cases of severe OHSS . Basal LH/FSH ratio was significantly higher in the pregnant group of patients than in nonpregnant women . Conclusions : Stepwise and chronic low-dose administration of FSH is a safe and effective method for treatment of WHO group II anovulatory infertility , mainly in those patients having high LH/FSH ratios Treatment with low-dose follicle-stimulating hormone ( FSH ) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome ( PCOS ) , but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin . We undertook a r and omized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin ( hMG ) using a low-dose regimen in 30 women with PCOS . Each subject received a maximum of three cycles of either FSH or hMG . Ovulation occurred in 75 % of subjects and in 77 % of cycles induced with FSH and in 94 % of women , 85 % of cycles of those treated with hMG . A single dominant follicle developed in 70 % ( FSH ) and 65 % ( hMG ) of cycles , respectively . Five singleton pregnancies occurred in each group . This study shows that low-dose FSH and hMG are equally successful in inducing ovulation , suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation OBJECTIVE To predict the FSH response ( threshold ) dose in normogonadotropic , anovulatory infertile women undergoing gonadotropin induction of ovulation . DESIGN Prospect i ve longitudinal clinical study . SETTING Specialist academic fertility unit . PATIENT(S ) Normogonadotropic , oligoamenorrheic , infertile women who were resistant to clomiphene citrate or in whom clomiphene citrate therapy had failed . INTERVENTION(S ) Daily exogenous FSH administration in a low-dose , step-up regimen . MAIN OUTCOME MEASURE(S ) The FSH dose on the day of ovarian response ( follicle growth > 10 mm in diameter ) . RESULT ( S ) Multivariate analysis was used to devise the following equation to predict the individual FSH response dose ( 75 to > 187 IU/d ) before initiation of therapy : [ 4 body mass index ( in kg/m(2 ) ) ] + [ 32 clomiphene citrate resistance ( yes = 1 or no = 0 ) ] + [ 7 initial free insulin-like growth factor-I ( in ng/mL ) ] + [ 6 initial serum FSH level ( in IU/L ) ] - 51 . The SE of the predicted dose is 35 IU . CONCLUSION ( S ) The individual FSH response dose for gonadotropin induction of ovulation in anovulatory infertile women can be predicted on the basis of initial screening characteristics . The prediction model developed in this study may increase the safety and efficiency of low-dose gonadotropin protocol s ( step-up and step-down ) by correctly determining the appropriate starting dose for a given patient The choice of treatment for clomiphene-resistant anovulation associated with polycystic ovary syndrome ( PCOS ) is presently arbitrary and selection criteria are not available . A total of 144 women with anovulatory infertility associated with PCOS who failed to conceive on clomiphene were treated with either pure follicle stimulating hormone ( FSH ) ( n = 29 ) , or human menopausal gonadotrophin ( HMG ) ( n = 60 ) , or gonadotrophin-releasing hormone analogue ( GnRHa ) and HMG ( n = 55 ) . Analysis of 306 treatment cycles and 53 pregnancies revealed a cumulative conception rate at 4 months of 23 % with FSH , 47 % with HMG and 69 % with GnRHa + HMG . The miscarriage rate was highest in the HMG group ( 44 % ) and consequently the cumulative live birth rate was superior when GnRHa was used in combination with HMG . There were no significant differences in the basal clinical and endocrinological features of those who conceived compared with those who did not , either in the whole group , or in the individual treatment groups . Thus , the choice of treatment for clomiphene-resistant women with PCOS can not be guided by the basal clinical or endocrinological features of this heterogeneous syndrome with the present state or knowledge OBJECTIVE To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve pilot study . SETTING Outpatient . PATIENT(S ) Twenty-two previously oligoamenorrheic , nondiabetic women with PCOS ; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin . INTERVENTION(S ) Metformin , 1.5 - 2.55 g/day , throughout pregnancy . MAIN OUTCOME MEASURE(S ) Rates of first-trimester spontaneous abortion and teratogenicity . RESULT ( S ) Before metformin , 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions ( 73 % ) . While receiving metformin , these 10 women had 6 normal live births ( 60 % ) , 1 spontaneous abortion ( 10 % ) , and 3 normal ongoing pregnancies ( 30 % ) ( all > or = 13 weeks ; median gestation , 23 weeks ) . Among women receiving metformin , including those with live births and normal pregnancy for at least the first trimester , 1 of 10 ( 10 % ) had first-trimester spontaneous abortion compared with 73 % in 22 previous pregnancies without metformin ( P<.002 ) . To date , the 19 women receiving metformin have had no adverse maternal side effects , and no birth defects have occurred ; 9 ( 47 % ) had normal term live births , 2 ( 11 % ) had normal and appropriate for gestational age births ( one at 33 and one at 35 weeks ) , 6 ( 32 % ) have ongoing normal pregnancies lasting longer than the first trimester , and 2 ( 10.5 % ) had first-trimester spontaneous abortions . Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies ( median gestation , 23 weeks ) . Among women who received metformin before conception , reductions in insulin and plasminogen activator inhibitor activity were correlated ( r=0.65 , P=.04 ) . CONCLUSION ( S ) Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic OBJECTIVE To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate ( CC ) . DESIGN Prospect i ve longitudinal single-center study . SETTING Specialist academic fertility unit . PATIENT(S ) Two hundred fifty-nine couples with a history of infertility , oligoamenorrhea , and normal follicle-stimulating hormone ( FSH ) concentrations who have not been previously treated with any ovulation-induction medication . INTERVENTION(S ) 50 , 100 , or 150 mg of oral CC per day , for 5 subsequent days per cycle . MAIN OUTCOME MEASURE(S ) Conception leading to live birth after CC administration . RESULT ( S ) After receiving CC , 98 ( 38 % ) women conceived , leading to live birth . The cumulative live birth rate within 12 months was 42 % for the total study population and 56 % for the ovulatory women who had received CC . Factors predicting the chances for live birth included free and rogen index ( testosterone/sex hormone-binding globulin ratio ) , body mass index , cycle history ( oligomenorrhea versus amenorrhea ) , and the woman 's age . CONCLUSION ( S ) It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram . Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility . Alternative first line of treatment options could be considered for some women who have limited chances for success The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial . The present prospect i ve longitudinal follow-up study was design ed to identify whether certain criteria assessed during st and ardized initial screening could predict the response to ovulation induction with clomiphene citrate ( CC ) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility . Serum FSH levels were within the normal range ( 1 - 10 IU/L ) , and all patients underwent spontaneous or progestin-induced withdrawal bleeding . Initial CC doses were 50 mg daily for 5 days starting on cycle day 3 . In the case of an absent response , doses were increased to 100 and 150 mg daily in subsequent cycles . First ovulation with CC was used as the end point . After a complete follow-up ( in the case of a nonresponse , at least 3 treatment cycles with daily CC doses up to 150 mg ) , 156 patients ( 78 % ) ovulated . The free and rogen index ( FAI = testosterone/sex hormone-binding globulin ratio ) , body mass index ( BMI ) , cycle history ( oligomenorrhea vs. amenorrhea ) , serum and rogen ( testosterone and /or and rostenedione ) levels , and mean ovarian volume assessed by transvaginal sonography were all significantly different ( P < 0.01 ) in responders from those in nonresponders . FAI was chosen to be the best predictor in univariate analysis . The area under the receiver operating characteristics curve in a multivariate prediction model including FAI , BMI , cycle history , and mean ovarian volume was 0.82 . Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics , such as FAI , BMI , cycle history ( oligomenorrhea or amenorrhea ) , and mean ovarian volume . These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone ( LH ) which has been implicated in the aetiology of early pregnancy loss . Although 82 % of women with recurrent early loss have polycystic ovaries on ultrasound imaging , r and om serum LH concentrations are normal . In the present study , we have obtained further information from serial sample s concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women . Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated ; 81 % of them and one of ten control subjects had polycystic ovaries . Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone ( FSH ) levels were similar in both groups . Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge ; one control subject had a premature LH surge . Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group , the difference in LH being greatest in the early luteal phase . Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss ; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion . These data demonstrate abnormalities in LH secretion in 81 % of women with recurrent fetal loss . Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly , or indirectly by causing an elevation in testosterone and oestrogen levels This follow-up study evaluated whether initial screening characteristics predict treatment outcome of gonadotrophin induction of ovulation . One hundred and fifty-four women with normogonadotrophic anovulatory infertility for whom clomiphene citrate induction of ovulation was unsuccessful were included in the present study . Daily FSH injections were initiated on day 3 - 5 after spontaneous or progestagen-induced withdrawal bleeding . In most patients , a dose finding low-dose step-up regimen was applied during the first treatment cycle in order to identify the individual FSH response dose . In all subsequent cycles , a step-down protocol was applied . Initial serum concentrations of LH , testosterone and and rostenedione were significant predictors for the probability of multi-follicular development . FSH treatment result ed in a total of 67 ( 44 % ) ongoing pregnancies . Comparing those women who did , versus those who did not , achieve an ongoing pregnancy in a multivariate Cox regression analysis , initial serum insulin-like growth factor-I ( IGF-I ) , testosterone and women 's age entered into the final model ( AUC = 0.67 ) . The individual treatment outcome following gonadotrophin induction of ovulation may be predicted by initial screening characteristics The present prospect i ve follow-up study was design ed to identify whether clinical , endocrine , or ultrasound characteristics assessed by st and ardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate ( CC ) medication . Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease . Daily CC doses of 50 mg ( increasing up to 150 mg in case of absent ovarian response ) from cycle days 3 - 7 were used . First conception ( defined as a positive urinary pregnancy test ) was the end point for this study . A cumulative conception rate of 73 % was reached within 9 CC-induced ovulatory cycles . Patients who did conceive presented more frequently with lower age ( P < 0.0001 ) and amenorrhea ( P < 0.05 ) upon initial screening . In a univariate analysis , patients with elevated initial serum LH concentrations ( > 7.0 IU/L ) had a higher probability of conceiving ( P < 0.01 ) . In a multivariate analysis , age and cycle history ( oligomenorrhea vs. amenorrhea ) were identified as the only significant parameters for prediction of conception . These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea . Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients ( body weight and hyper and rogenemia , as shown previously ) are distinctly different from predictors of conception in ovulatory CC patients ( age and the severity of cycle abnormality ) . This disparity suggests that the FSH threshold ( magnitude of FSH required for stimulation of ongoing follicle growth and ovulation ) and oocyte quality ( chances for conception in ovulatory cycles ) may be differentially regulated Therapeutic approaches to chronic anovulation from polycystic ovaries in clomiphene-resistant infertile patients are under debate . This study discusses evidence that supports the possible predictive value of serum basal level of and rostenedione in the choice of the better therapy between laparoscopic ovarian electrocautery and ovulation induction . Lower and rostenedione levels seem to be correlated with a better ovarian response after ovulation induction with gonadotropins , while high and rostenedione levels are associated with a higher incidence of conception after laparoscopic ovarian electrocautery . Obesity does not seem to represent a hindrance to laparoscopic treatment Eighty‐eight clomiphene citrate‐resistant infertile patients with oligomeno‐rrhoea or amenorrhoea attributable to polycystic ovarian disease were divided at r and om into three groups . Twenty‐nine patients were treated with ovarian electrocautery , 30 with human menopausal gonadotropins ( hMG ) and 29 with pure follicle stimulating hormone ( FSH ) . Successful ovulation was induced in 71‐4 , 70‐6 and 66‐7 % of the cycles in the groups respectively . Ten patients conceived after electrocautery and pure FSH therapy while 15 conceived after hMG medication ( chi‐squared = 1 ‐6464 , P = 0–439 ) . The six‐cycle cumulative pregnancy rate in the three consecutive groups was 521 , 55‐4 and 38‐3 % . Four further pregnancies were achieved after treating 10 patients in the electrocautery group with clomiphene citrate ( 100 mg/day for 5 days ) for 25 cycles . The rate of pregnancy wastage in the corresponding groups was 21‐4 , 53‐3 and 40 % ( chi‐squared = 3–127 , P = 0–2039 ) . Ovarian electrocautery is equally effective as hMG and pure FSH in the treatment of PCO patients resistant to clomiphene citrate therapy The aim of the presented study was to compare FSH threshold levels and ovarian response to stimulation with one of two st and ard increments of exogenous FSH above the threshold in patients with polycystic ovary syndrome ( PCOS ) ( n = 12 ) and eumenorrheic women ( n = 11 ) . The individual FSH threshold was determined by treatment according to a low-dose , step-up protocol with urinary FSH ( Metrodin ; Ares Serono , Geneva , Switzerl and ) . In a subsequent treatment cycle , six PCOS patients and six eumenorrheic women were r and omly assigned to double-blind treatment with the threshold dose plus 1/2 ampoule ; the other six PCOS patients and five eumenorrheic women were treated with 1 ampoule above the threshold dose . Determination of threshold levels showed no significant differences in median and range between PCOS patients and eumenorrheic women . The number of follicles on the day of human chorionic gonadotropin administration showed no significant correlation with the increase in FSH level above the threshold level . Irrespective of the dose given , the number of follicles in the PCOS group was significantly higher than in eumenorrheic women . The higher sensitivity for gonadotropin stimulation in patients with PCOS compared with women with regular menstrual cycles therefore appears not to be dependent on differences in FSH threshold level , but rather on the larger size of the FSH sensitive cohort of small antral follicles OBJECTIVE To compare the safety and efficacy of recombinant FSH ( follitropin beta , Puregon ; NV Organon , Oss , the Netherl and s ) and urinary FSH ( urofollitropin , Metrodin ; Ares-Serono , Geneva , Switzerl and ) . DESIGN A prospect i ve , multicenter , assessor-blind , r and omized , clinical trial . SETTING Twelve European infertility clinics . PATIENT(S ) One hundred seventy-two women ( recombinant FSH : n = 105 ; urinary FSH : n = 67 ) with clomiphene citrate-resistant normogonadotropic chronic anovulation ( World Health Organization group II ) . INTERVENTION(S ) Eligible subjects were r and omized ( ratio of recombinant to urinary FSH , 3:2 ) and treated for a maximum of three cycles . A low-dose step-up regimen was used , with 75 IU of FSH given IM daily for a maximum of 14 days and , if needed , weekly increments of half an ampule given thereafter until the threshold dose for follicular development was achieved . MAIN OUTCOME MEASURE(S ) Cumulative ovulation rate after three cycles , total FSH dose , and treatment period needed to achieve ovulation . RESULT ( S ) The cumulative ovulation rates after three treatment cycles were 95 % and 96 % for the recombinant and urinary FSH groups , respectively . Overall , ovulation was seen in 155 of 223 treatment cycles ( 69.5 % ) in the recombinant FSH group , compared with 92 of 138 treatment cycles ( 66.7 % ) in the urinary FSH group . In the first cycle , a statistically significantly lower total dose ( 750 versus 1,035 IU ) and a shorter treatment period ( 10 versus 13 days ) were needed in the recombinant FSH group to reach ovulation . Only one case of ovarian hyperstimulation syndrome led to hospitalization . Two sets of twins ( one in each treatment group ) and one set of triplets ( in the recombinant FSH group ) were born . CONCLUSION ( S ) Recombinant FSH ( Puregon ) is more efficient than urinary FSH ( Metrodin ) in inducing follicular development |
11,247 | 21,709,590 | There is some evidence that histology is prognostic for survival .
There is evidence from multiple r and omized clinical trials to recommend the following : histologic subtype is predictive of treatment efficacy and for some agents toxicity .
Clinical data on K-RAS mutations are inconsistent , therefore testing is not recommended .
There is insufficient evidence to recommend other biomarker testing .
No biomarkers to date reliably predict improved efficacy for anti-VEGF therapy . | INTRODUCTION Greater underst and ing of molecular pathways important in cell growth and proliferation of thoracic malignancies , particularly non-small cell lung cancer ( NSCLC ) , has result ed in intense clinical and translational research .
There is now considerable interest in personalizing treatment based on an underst and ing of tumor histology and molecular abnormalities .
However , there is a multiplicity of data , often with discordant results result ing in confusion and uncertainty among clinicians .
CONCLUSIONS Assessment of NSCLC biomarkers is becoming increasingly important . | BACKGROUND Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy Background Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance . BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel . We have retrospectively examined the effect of RRM1 , RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer ( NSCLC ) patients . Methodology and Principal Findings Tumor sample s were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a r and omized trial . RRM1 , RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response , time to progression and survival . As BRCA1 levels increased , the probability of response increased ( Odds Ratio [ OR ] , 1.09 : p = 0.01 ) and the risk of progression decreased ( hazard ratio [ HR ] , 0.99 ; p = 0.36 ) . As RRM1 and RRM2 levels increased , the probability of response decreased ( RRM1 : OR , 0.97 ; p = 0.82 ; RRM2 : OR , 0.94 ; p<0.0001 ) and the risk of progression increased ( RRM1 : HR , 1.02 ; p = 0.001 ; RRM2 : HR , 1.005 ; p = 0.01 ) . An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels , with times to progression of 10.13 , 4.17 and 2.30 months ( p = 0.001 ) . Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy . Conclusions The mRNA expression of BRCA1 , RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospect i ve studies Purpose : No chemotherapy regimen , including the widely used combination of gemcitabine/cisplatin , confers significantly improved survival over any other in metastatic non-small cell lung cancer ( NSCLC ) ; however , the selection of patients according to key genetic characteristics can help to tailor chemotherapy . Ribonucleotide reductase subunit M1 ( RRM1 ) is involved in DNA synthesis and repair and in gemcitabine metabolism , and the excision repair cross-complementing group 1 ( ERCC1 ) gene has been related to cisplatin activity . Experimental Design : Patients were part of a large r and omized trial carried out from September 1998 to July 2000 , comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide . We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded sample s obtained from bronchoscopy by real-time quantitative reverse transcription-PCR . Results were correlated with survival using the Kaplan-Meier method . Results : A total of 100 patients were assessed . There was a strong correlation between RRM1 and ERCC1 mRNA expression levels ( Spearman r = 0.410 ; P < 0.001 ) . In the gemcitabine/cisplatin arm , patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [ 13.7 versus 3.6 months ; 95 % confidence interval ( CI ) , 9.6–17.8 months ; P = 0.009 ] . Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 ( not reached ) , than among those with high levels of both genes ( 6.8 months ; 95 % CI , 2.6–11.1 months ; P = 0.016 ) . Conclusions : RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients . Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy . Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel . Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis PURPOSE The International Adjuvant Lung Cancer Trial ( IALT ) demonstrated that adjuvant cisplatin-based chemotherapy improves the survival of patients with completely resected non-small-cell lung cancer ( NSCLC ) . The purpose of our study was to determine whether cell cycle regulators are of prognostic and /or predictive value in patients who were enrolled onto the IALT . PATIENTS AND METHODS Expression of p27Kip1 , p16INK4A , cyclin D1 , cyclin D3 , cyclin E , and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients . Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic parameters . RESULTS There was a relationship between p27Kip1 status and benefit of cisplatin-based chemotherapy ( test for interaction , P = .02 ) . Among patients with p27Kip1-negative tumors , cisplatin-based chemotherapy result ed in longer overall survival compared with controls ( adjusted hazard ratio [ HR ] for death = 0.66 ; 95 % CI , 0.50 to 0.88 ; P = .006 ) . In patients with p27Kip1-positive tumors , overall survival was not different between patients treated with cisplatin-based chemotherapy and controls ( adjusted HR for death = 1.09 ; 95 % CI , 0.82 to 1.45 ; P = .54 ) . The other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy . None of these biomarkers was significantly associated with overall survival of the patients in the total study population . CONCLUSION NSCLC patients with p27Kip1-negative tumors benefit from adjuvant cisplatin-based chemotherapy after complete tumor resection . Before establishing p27Kip1 as a routine marker for selection of patients for adjuvant chemotherapy , the predictive value of p27Kip1 has to be confirmed in patients from other trials BACKGROUND We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer . METHODS We r and omly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation . The primary end point was overall survival ; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen . RESULTS A total of 482 patients underwent r and omization to vinorelbine plus cisplatin ( 242 patients ) or observation ( 240 ) ; 45 percent of the patients had pathological stage IB disease and 55 percent had stage II , and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1 . In both groups , the median age was 61 years , 65 percent were men , and 53 percent had adenocarcinomas . Chemotherapy caused neutropenia in 88 percent of patients ( including grade 3 febrile neutropenia in 7 percent ) and death from toxic effects in two patients ( 0.8 percent ) . Nonhematologic toxic effects of chemotherapy were fatigue ( 81 percent of patients ) , nausea ( 80 percent ) , anorexia ( 55 percent ) , vomiting ( 48 percent ) , neuropathy ( 48 percent ) , and constipation ( 47 percent ) , but severe ( grade 3 or greater ) toxic effects were uncommon ( < 10 percent ) . Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group ( 94 vs. 73 months ; hazard ratio for death , 0.69 ; P=0.04 ) , as was relapse-free survival ( not reached vs. 46.7 months ; hazard ratio for recurrence , 0.60 ; P<0.001 ) . Five-year survival rates were 69 percent and 54 percent , respectively ( P=0.03 ) . CONCLUSIONS Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . 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 BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel . The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 . PURPOSE This report describes the quality of life ( QOL ) findings of a r and omized placebo controlled study of erlotinib , an epidermal growth factor receptor inhibitor , in patients with non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This double-blind phase III trial r and omly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo , with survival as the primary study outcome . QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13 . The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms : cough , dyspnea , and pain . RESULTS Survival was significantly longer ( hazard ratio , 0.70 ; P < .0001 ) in the erlotinib arm . Compliance with QOL was 87 % at baseline and more than 70 % during treatment . Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms ( 4.9 v 3.7 months for cough [ P = .04 ] ; 4.7 v 2.9 months for dyspnea [ P = .04 ] , and 2.8 v 1.9 months for pain [ P = .03 ] ) . QOL response analyses showed that 44 % , 34 % , and 42 % of patients receiving erlotinib had improvement in these three symptoms , respectively . This was accompanied by a significant improvement in the physical function ( 31 % erlotinib v 19 % placebo , P = .01 ) , and global QOL ( 35 % v 26 % , P < .0001 ) . Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease ( P < .01 ) . CONCLUSION Erlotinib not only improves survival in previously treated patients with NSCLC , but also improves tumor-related symptoms and important aspects of QOL 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 We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer PURPOSE To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omized preoperatively to receive adjuvant postoperative radiotherapy ( Arm A ) or radiotherapy plus concurrent chemotherapy ( Arm B ) . p53 protein expression was studied by immunohistochemistry ( IHC ) and p53 mutations in exons 5 to 8 were evaluated by single-str and conformational analysis . K-ras mutations in codons 12 , 13 , and 61 were determined using engineered restriction fragment length polymorphisms . RESULTS Four hundred eighty-eight patients were entered onto E3590 ; 197 tumors were assessable for analysis . Neither presence nor absence of p53 mutations , p53 protein expression , or K-ras mutations correlated with survival or progression-free survival . There was a trend toward improved survival for patients with wildtype K-ras ( median , 42 months ) compared with survival of patients with mutant K-ras who were r and omized to chemotherapy plus radiotherapy ( median , 25 months ; P = .09 ) . Multivariate analysis revealed only age and tumor stage to be significant prognostic factors , although there was a trend bordering on statistical significance for K-ras ( P = .066 ) . Analysis of survival difference by p53 by single-str and ed conformational polymorphism and IHC , interaction of p53 and K-ras , interaction of p53 and treatment arm , nodal station , extent of surgery , weight loss , and histology did not reach statistical significance . CONCLUSION p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC . K-ras mutations may be a weak prognostic marker . p53 or K-ras should not be routinely used in the clinical management of these patients 8007 Background : The multinational , r and omized , phase III FLEX study compared cisplatin/vinorelbine ( CT ) plus the EGFR- antibody , cetuximab ( Erbitux ) , with CT alone in the 1st-line treatment of patients ( pts ) with advanced EGFR-expressing NSCLC and demonstrated a statistically significant OS benefit for the cetuximab combination . We hypothesized that KRAS mutation status is predictive for cetuximab efficacy and enables optimal use of cetuximab . The relationship between early-onset acne-like rash ( ie rash that developed ≤21 days of treatment initiation ) and OS time of pts treated with CT and cetuximab was also evaluated . METHODS Archived tumor sample s from 554/1125 pts were available . Genomic DNA derived from formalin-fixed paraffin embedded tumor tissue was analyzed for KRAS using an LNA-mediated qPCR clamping assay capable of detecting oncogenic mutations at codons 12 and 13 . The Kaplan-Meier method was used to estimate OS time and PFS time in pts with KRAS wild-type ( wt ) and mutant ( mt ) tumors for each treatment arm . All pts treated with cisplatin/vinorelbine plus cetuximab who were alive at 21 days were included in a l and mark analysis evaluating the relationship between early-onset acne-like rash and OS time . RESULTS KRAS results were obtained from 379 pts . A KRAS mutation was detected in 72 ( 19 % ) pts . The comparison of the cetuximab treatment effects in pts with KRAS wt tumors and pts with KRAS mt tumors showed no marked differences with regard to OS or PFS . A total of 518 pts were included in the l and mark analysis . Pts treated with cetuximab who developed early acne-like rash of any grade ( grade 1 - 3 ; 56 % , n=290 ) had a longer median OS than those without acne-like rash ( n=228 ) ( median [ 95 % CI ] : 15.0 months [ 12.8 - 16.4 ] vs 8.8 months [ 7.6 - 11.1 ] ; HR [ 95 % CI ] : 0.63 [ 0.52 - 0.77 ] ; p<0.001 ) . Analysis of EGFR FISH is ongoing and results will be presented . CONCLUSIONS Clinical data from the FLEX study do not support the hypothesis that KRAS mutation status is predictive for cetuximab efficacy when combined with 1st- line chemotherapy in advanced NSCLC , whereas early acne-like rash of any grade appears to be associated with better outcome in pts treated with platinum-based chemotherapy plus cetuximab in this setting . [ Table : see text ] BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase ( ALK ) are present in a subgroup of non-small-cell lung cancers , representing 2 to 7 % of such tumors . We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib ( PF-02341066 ) , an orally available small-molecule inhibitor of the ALK tyrosine kinase . METHODS After screening tumor sample s from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements , we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial . Most of the patients had received previous treatment . These patients were enrolled in an exp and ed cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles . Patients were assessed for adverse events and response to therapy . RESULTS Patients with ALK rearrangements tended to be younger than those without the rearrangements , and most of the patients had little or no exposure to tobacco and had adenocarcinomas . At a mean treatment duration of 6.4 months , the overall response rate was 57 % ( 47 of 82 patients , with 46 confirmed partial responses and 1 confirmed complete response ) ; 27 patients ( 33 % ) had stable disease . A total of 63 of 82 patients ( 77 % ) were continuing to receive crizotinib at the time of data cutoff , and the estimated probability of 6-month progression-free survival was 72 % , with no median for the study reached . The drug result ed in grade 1 or 2 ( mild ) gastrointestinal side effects . CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement result ed in tumor shrinkage or stable disease in most patients . ( Funded by Pfizer and others ; Clinical Trials.gov number , NCT00585195 . ) 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 BACKGROUND Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor ( EGFR ) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib . However , whether gefitinib is better than st and ard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain . METHODS We did an open label , phase 3 study ( WJTOG3405 ) with recruitment between March 31 , 2006 , and June 22 , 2009 , at 36 centres in Japan . 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations ( either the exon 19 deletion or L858R point mutation ) were r and omly assigned , using a minimisation technique , to receive either gefitinib ( 250 mg/day orally ; n=88 ) or cisplatin ( 80 mg/m(2 ) , intravenously ) plus docetaxel ( 60 mg/m(2 ) , intravenously ; n=89 ) , administered every 21 days for three to six cycles . The primary endpoint was progression-free survival . Survival analysis was done with the modified intention-to-treat population . This study is registered with UMIN ( University Hospital Medical Information Network in Japan ) , number 000000539 . FINDINGS Five patients were excluded ( two patients were found to have thyroid and colon cancer after r and omisation , one patient had an exon 18 mutation , one patient had insufficient consent , and one patient showed acute allergic reaction to docetaxel ) . Thus , 172 patients ( 86 in each group ) were included in the survival analyses . The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup , with a median progression-free survival time of 9.2 months ( 95 % CI 8.0 - 13.9 ) versus 6.3 months ( 5.8 - 7.8 ; HR 0.489 , 95 % CI 0.336 - 0.710 , log-rank p<0.0001 ) . Myelosuppression , alopecia , and fatigue were more frequent in the cisplatin plus docetaxel group , but skin toxicity , liver dysfunction , and diarrhoea were more frequent in the gefitinib group . Two patients in the gefitinib group developed interstitial lung disease ( incidence 2.3 % ) , one of whom died . INTERPRETATION Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel . FUNDING West Japan Oncology Group ( WJOG ) : a non-profit organisation supported by unrestricted donations from several pharmaceutical companies Purpose : TRIBUTE was a phase III trial evaluating the addition of erlotinib to carboplatin and paclitaxel as a first-line treatment for advanced non – small cell lung cancer that did not meet its primary end point of improving overall survival . Here , we assess the value of using epidermal growth factor receptor ( EGFR ) gene copy number in tumor biopsy sample s , as determined by fluorescence in situ hybridization ( FISH ) , as a predictor of treatment outcome . Methods : EGFR FISH analysis was done using LSI EGFR SpectrumOrange/CEP7 SpectrumGreen probe . Results : Of 275 sample s , 245 ( 89.1 % ) were successfully analyzed by FISH . One hundred ( 40.8 % ) of patients were EGFR FISH(+ ) . Median overall survival was not different between FISH(+ ) and FISH(− ) patients in either the chemotherapy+erlotinib arm or the chemotherapy+placebo arm . In FISH(+ ) patients , median time to progression ( TTP ) was 6.3 months in the erlotinib arm versus 5.8 months in the placebo arm ( hazard ratio , 0.59 ; 95 % confidence interval , 0.35 - 0.99 ; P = 0.0430 ) ; in FISH(− ) patients , median TTP was 4.6 months versus 6.0 months ( hazard ratio , 1.42 ; 95 % confidence interval , 0.95 - 2.14 ; P = 0.0895 ; treatment interaction test , P = 0.007 ) . After 6 months of treatment , a notable separation of the TTP curves in favor of erlotinib emerged . Objective response rates were 11.6 % versus 29.8 % in FISH(+ ) patients ( chemotherapy+erlotinib arm versus chemotherapy+placebo arm ; P = 0.0495 ) and 21.8 % versus 25.4 % , respectively , for FISH(− ) patients ( P = 0.6954 ) . Conclusions : EGFR gene copy number by FISH did not predict survival benefit . However , among EGFR FISH(+ ) patients , TTP was longer in patients who received erlotinib and continued to receive it after completing first-line therapy 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 PURPOSE p53 and RAS are multifunctional proteins that are critical to cell cycle regulation , apoptosis , cell survival , gene transcription , response to stress , and DNA repair . We have evaluated the prognostic and predictive value of p53 gene/protein aberrations using tumor sample s from JBR.10 , a North American phase III intergroup trial that r and omly assigned 482 patients with completely resected stage IB and II non-small-cell lung cancer ( NSCLC ) to receive four cycles of adjuvant cisplatin plus vinorelbine or observation alone . METHODS p53 protein expression was evaluated by immunohistochemistry . Mutations in exons 5 to 9 of the p53 gene were determined by denaturing high-performance liquid chromatography and confirmed by sequencing . RAS mutations were identified by allelic specific oligonucleotide hybridization . RESULTS Of 253 patients , 132 ( 52 % ) were positive for p53 protein overexpression . Untreated p53-positive patients had significantly shorter overall survival than did patients with p53-negative tumors ( hazard ratio [ HR ] = 1.89 ; 95 % CI , 1.07 to 3.34 ; P = .03 ) . However , these p53-positive patients also had a significantly greater survival benefit from adjuvant chemotherapy ( HR = 0.54 ; P = .02 ) compared with patients with p53-negative tumors ( HR = 1.40 ; P = .26 ; interaction P = .02 ) . Mutations of p53 and RAS genes were found in 124 ( 31 % ) of 397 and 117 ( 26 % ) of 450 patients , respectively . Mutations in these genes were neither prognostic for survival nor predictive of a differential benefit from adjuvant chemotherapy . CONCLUSION p53 protein overexpression is a significant prognostic marker of shortened survival , and also a significant predictive marker for a differentially greater benefit from adjuvant chemotherapy in completely resected NSCLC patients PURPOSE There is an unmet need for biomarkers for identifying patients likely to benefit from anticancer treatments , selecting dose , and underst and ing mechanisms of resistance . Plasma vascular endothelial growth factor ( VEGF ) and soluble VEGF receptor 2 ( sVEGFR-2 ) are known to be modulated by VEGF pathway inhibitors . It is unknown whether chemotherapy or VEGFR inhibitor/chemotherapy combinations induce changes in these or other cytokines and angiogenic factors ( CAFs ) and whether such changes could be markers of benefit . METHODS Thirty-five plasma CAFs were analyzed using multiplexed bead arrays and enzyme-linked immunosorbent assays from 123 patients with non-small-cell lung cancer in a r and omized phase II study who received v and etanib , a VEGFR and epidermal growth factor receptor inhibitor , monotherapy carboplatin and paclitaxel ( CP ) , or the combination ( VCP ) . Changes in CAFs at days 8 , 22 , and 43 from baseline were correlated with progression risk . RESULTS VEGF increased and sVEGFR-2 decreased by day 43 in the v and etanib arm , whereas a distinct pattern was observed in the CP and VCP arms , with significant decreases in interleukin ( IL ) -12 , IL-1 receptor antagonist , and matrix metalloproteinase 9 ( MMP-9 ) and increased macrophage chemoattractant protein 1 . In each treatment arm , changes in different markers were associated with progression risk . For example , increases in IL-8 with VCP , MMP-9 with CP , and VEGF with v and etanib monotherapy were associated with increased progression risk , and increase in intercellular adhesion molecule 1 with v and etanib was associated with decreased risk . CONCLUSION V and etanib and chemotherapy treatment led to distinct patterns of CAF changes ; the combination resembled chemotherapy alone . Changes in specific CAFs correlated with clinical outcome , but markers differed for each treatment arm . CAF profiling may provide insights into the biologic effects of treatment and identify drug-specific markers of activity and clinical benefit BACKGROUND Use of cetuximab , a monoclonal antibody targeting the epidermal growth factor receptor ( EGFR ) , has the potential to increase survival in patients with advanced non-small-cell lung cancer . We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer . METHODS In a multinational , multicentre , open-label , phase III trial , chemotherapy-naive patients ( > or=18 years ) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy . Chemotherapy was cisplatin 80 mg/m(2 ) intravenous infusion on day 1 , and vinorelbine 25 mg/m(2 ) intravenous infusion on days 1 and 8 of every 3-week cycle ) for up to six cycles . Cetuximab-at a starting dose of 400 mg/m(2 ) intravenous infusion over 2 h on day 1 , and from day 8 onwards at 250 mg/m(2 ) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred . The primary endpoint was overall survival . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS Between October , 2004 , and January , 2006 , 1125 patients were r and omly assigned to chemotherapy plus cetuximab ( n=557 ) or chemotherapy alone ( n=568 ) . Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group ( median 11.3 months vs 10.1 months ; hazard ratio for death 0.871 [ 95 % CI 0.762 - 0.996 ] ; p=0.044 ) . The main cetuximab-related adverse event was acne-like rash ( 57 [ 10 % ] of 548 , grade 3 ) . INTERPRETATION Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer . FUNDING Merck BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo . At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin PURPOSE This phase III , multicenter , r and omized , placebo-controlled trial assessed the efficacy and safety of sorafenib , an oral multikinase inhibitor , in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Nine hundred twenty-six patients were r and omly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2 ) ( CP ) on day 1 , followed by either sorafenib 400 mg twice a day ( n = 464 , arm A ) or placebo ( n = 462 , arm B ) on days 2 to 19 . The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day . The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival and tumor response . RESULTS Overall demographics were balanced between arms ; 223 patients ( 24 % ) had squamous cell histology . On the basis of a planned interim analysis , median OS was 10.7 months in arm A and 10.6 months in arm B ( hazard ratio [ HR ] = 1.15 ; 95 % CI , 0.94 to 1.41 ; P = .915 ) . The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point . A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B ( HR = 1.85 ; 95 % CI , 1.22 to 2.81 ) . Main grade 3 or 4 sorafenib-related toxicities included rash ( 8.4 % ) , h and -foot skin reaction ( 7.8 % ) , and diarrhea ( 3.5 % ) . CONCLUSION No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC PURPOSE Most cases of non-small-cell lung cancer ( NSCLC ) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor ( EGFR ) , but the predictive value of these mutations has not been defined in large clinical trials . The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II ( IDEAL ) and phase III ( INTACT ) trials of gefitinib . PATIENTS AND METHODS We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification , another genetic abnormality in NSCLC . RESULTS EGFR mutations correlated with previously identified clinical features of gefitinib response , including adenocarcinoma histology , absence of smoking history , female sex , and Asian ethnicity . No such association was seen in patients whose tumors had EGFR amplification , suggesting that these molecular markers identify different biologic subsets of NSCLC . In the IDEAL trials , responses to gefitinib were seen in six of 13 tumors ( 46 % ) with an EGFR mutation , two of seven tumors ( 29 % ) with amplification , and five of 56 tumors ( 9 % ) with neither mutation nor amplification ( P = .001 for either EGFR mutation or amplification v neither abnormality ) . Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype . CONCLUSION EGFR mutations and , to a lesser extent , amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib . The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available Introduction : The emergence of treatments for non-small cell lung carcinoma ( NSCLC ) with differential efficacy and toxicity between subtypes has highlighted the importance of specific pathologic NSCLC subtyping . Most NSCLCs are inoperable , and pathologic diagnosis is made only on small tissue sample s that are prone to diagnostic inaccuracy . In a substantial proportion of cases , st and ard morphology can not specifically subtype the tumor , necessitating a diagnosis of NSCLC-not otherwise specified ( NOS ) . Histochemical staining for mucin and immunohistochemical ( IHC ) identification of NSCLC subtype-associated markers could help predict the final subtype of resected NSCLCs diagnosed as NSCLC-NOS on preoperative bronchial biopsy sample s. Methods : Paraffin sections of 44 bronchial biopsy sample s diagnosed as NSCLC-NOS were stained for mucin ( Alcian blue/periodic acid Schiff ) and thyroid transcription factor 1 by IHC–(markers of adenocarcinoma ) , and for S100A7 , cytokeratin 5/6 , high molecular weight cytokeratins , and p63 proteins – markers of squamous cell carcinoma . A predictive staining panel was derived from statistical analysis after comparing staining profiles with the final postsurgical NSCLC subtype . This panel was prospect ively applied to 82 small biopsy sample s containing NSCLC . Results : True NSCLC subtype of undifferentiated NSCLC sample s was best predicted using Alcian blue/periodic acid Schiff plus p63 and thyroid transcription factor 1 IHC , allowing specific subtyping in 73 % of NSCLC-NOS cases with 86 % accuracy . When applied prospect ively , this staining panel showed 100 % concordance with specific NSCLC morphologic subtyping in small biopsies . Conclusion : This approach can facilitate treatment selection by accurately predicting the subtype in undifferentiated NSCLC biopsies , reducing to 7 % the proportion of cases without a definite or probable histologic subtype 8020 Background : The SATURN ( BO18192 ) study investigated whether erlotinib maintenance therapy improved PFS in patients ( pts ) with advanced NSCLC who had obtained clinical benefit from 1st-line chemotherapy . This study included a prospect i ve analysis of the prognostic/predictive value of several molecular markers . METHODS 889 pts with advanced NSCLC whose disease had not progressed following 4 cycles of 1st-line platinum-doublet chemotherapy were r and omized to erlotinib 150 mg/day or placebo . M and atory tumor specimens were collected at baseline and tested for EGFR protein expression using immunohistochemistry ( IHC ) , EGFR gene copy number using fluorescent in-situ hybridization ( FISH ) , and EGFR and KRAS somatic mutations using DNA sequencing . Pts were stratified according to EGFR IHC status ( any membranous staining in ≥10 % tumor cells used as cut-off ) ; the co- primary endpoint was PFS in EGFR IHC+ pts . Baseline whole blood sample s were obtained for genotyping of EGFR ( intron 1 CA-repeat polymorphisms ) . RESULTS In the overall population , erlotinib significantly prolonged PFS vs placebo ( HR 0.71 , p<.0001 ; primary endpoint ) . The co- primary endpoint was also met , with erlotinib significantly improving PFS in the EGFR IHC+ group ( HR 0.69 , p<.0001 ) . Many tumor sample s were assessable for molecular marker status ( see table ) . Biomarker data suggest that patients derived a PFS benefit with erlotinib irrespective of EGFR FISH or EGFR intron 1 CA-repeat status . The magnitude of benefit with erlotinib was similar in both KRAS-mutant and KRAS wild-type pts . CONCLUSIONS This is the largest biomarker analysis performed for erlotinib in a r and omized , placebo-controlled setting , and answers key scientific questions regarding the prognostic and predictive value of potential biomarkers of efficacy . Full data will be presented . [ Table : see text ] [ Table : see text ] 7526 Background : IFCT-0002 phase III trial compared two timings of CT in early lung cancer , all before surgery ( PRE ) versus PERIoperative , and two CT regimens , CDDP-Gem vs. CBDCA-Pac . 528 patients were r and omized . Paraffin embedded post- chemo pathological specimens were collected in the 490 non complete responder patients for tissue expression of the putative biomarker beta-tubulin III ( bTubIII ) . METHODS 423 surgical pathological specimens with enough remaining viable tumor tissue after neoadjuvant chemo were processed for immunohistochemistry as published in the Bio-IALT study . A semi-quantitative score was attributed taking account the number of stained cells and the intensity of staining . Semi-quantitative scores were studied as continuous variables , without any pre- determined cut-off . Multivariate analysis for progression-free ( PFS ) and overall survival ( OS ) were corrected with Bonferroni-Holm method for multiple analyses . Median follow-up was 42 months . RESULTS bTubIII was the only IHC marker significantly associated with poor PFS in univariate ( p=0.014 ) or multivariate analysis , adjusted for histology , T and stage ( HR= 1.50 [ 1.07 - 2.10 ] ; p=0.020 ) . In patients with a pathological specimen showing a bTubIII positive immunostaining , median PFS was 30.6 months , versus 60.1 months ( HR=1.46 [ 1.08 - 1.99 ] ) for bTubIII negative patients . bTubIII IHC score remained predictive of poor OS in univariate ( p= 0.0065 ) as in multivariate analysis ( p=0.019 with Bonferroni correction , HR=1.75 [ 1.15 - 2.68 ] ) . Median OS was not reached for bTubIII negative patients whereas it was 71.7 months in patients with bTubIII immunostaining of any intensity score ( HR=1.61 , [ 1.11 - 2.35 ] ) . CONCLUSIONS This study showed a dramatic negative prognostic impact for bTubIII immunostaining in resectable early lung cancer . A subset of bTubIII expressing patients with poor prognosis did not take any advantage from perioperative chemo . Hence , those patients could rather have beneficiated from personalized adjuvant treatment with alternative approaches . No significant financial relationships to disclose Background : Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer ( NSCLC ) . Excision repair cross-complementation group 1 ( ERCC1 ) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair . We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response , toxicity , and survival after platinum-based chemotherapy . Methods : Patients r and omized to a phase III trial of platinum-based chemotherapy were eligible for inclusion . Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology . Expression data were correlated with treatment response , toxicity , and overall survival . Results : Sixty-six patients were enrolled . No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy ( p = 0.794 ) or hematological toxicity . No statistically significant difference in median survival was demonstrated according to ERCC1 expression ( high expression , 415 days , 95 % confidence interval [ 95%CI ] : 197–633 days ; low expression , 327 days [ 95%CI : 211–433 days ] ; p = 0.801 ) . High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 ( 95 % CI 0.919–1.004 ; p = 0.08 ) . Conclusion : In contrast to recent publications , ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC . We explore potential reasons for this , including the need for cautious interpretation of mRNA expression data from archival material s and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism PURPOSE Although current treatment options for metastatic non-small-cell lung cancer ( NSCLC ) rely on cisplatin-based chemotherapy , individualized approaches to therapy may improve response or reduce unnecessary toxicity . Excision repair cross-complementing 1 ( ERCC1 ) has been associated with cisplatin resistance . We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response . PATIENTS AND METHODS From August 2001 to October 2005 , 444 stage IV NSCLC patients were enrolled . RNA was isolated from pretreatment biopsies , and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression . Patients were r and omly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment . Patients in the control arm received docetaxel plus cisplatin . In the genotypic arm , patients with low ERCC1 levels received docetaxel plus cisplatin , and those with high levels received docetaxel plus gemcitabine . The primary end point was the overall objective response rate . RESULTS Of 444 patients enrolled , 78 ( 17.6 % ) went off study before receiving one cycle of chemotherapy , mainly due to insufficient tumor tissue for ERCC1 mRNA assessment . Of the remaining 346 patients assessable for response , objective response was attained by 53 patients ( 39.3 % ) in the control arm and 107 patients ( 50.7 % ) in the genotypic arm ( P = .02 ) . CONCLUSION Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin . Additional studies are warranted to optimize method ologies for ERCC1 analysis in small tumor sample s and to refine a multibiomarker profile predictive of patient outcome Introduction : The dichotomization of non-small cell carcinoma ( NSCLC ) subtype into squamous ( SQCC ) and adenocarcinoma ( ADC ) has become important in recent years and is increasingly required with regard to management . The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospect ively analyzed series of patients undergoing investigation for suspected lung cancer . Methods : Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6 , P63 , thyroid transcription factor-1 , 34&bgr;E12 , and a D-PAS stain for mucin , to determine their value in refining diagnosis of NSCLC . After this test phase , two further pathologists independently review ed the cases using a refined panel that excluded 34&bgr;E12 because of its low specificity for SQCC , and refinement of diagnosis and concordance were assessed . Ten cases of ADC , including eight derived from cytologic sample s , were sent for EGFR mutation analysis . Results : There was refinement of diagnosis in 65 % of cases of NSCLC to either SQCC or ADC in the test phase . This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates . Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis . All sample s were adequate for analysis , and they all showed a wild-type EGFR genotype . Conclusion : A panel comprising cytokeratin 5/6 , P63 , thyroid transcription factor-1 , and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC . These small sample s , even cell pellets derived from transbronchial needle aspirates , seem to be adequate for EGFR mutation analysis 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 PURPOSE Severe ( grade > or= 3 ) pulmonary hemorrhage ( PH ) in advanced non-small-cell lung cancer was observed in two prospect i ve , r and omized , phase II ( N = 99 ) and phase III ( N = 878 ) trials of bevacizumab plus carboplatin and paclitaxel . Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH . PATIENTS AND METHODS Six patients with PH from the phase II trial , 15 potential PH patients with hemorrhage at any site from the phase III trial , and their matched controls were evaluated with review of baseline and on-treatment radiographs by an independent radiology facility , blinded to patient/control status . Patients with severe ( grade > or= 3 ) PH from each trial were matched with up to three controls based on sex , age group , histology ( phase II ) , or sex and age group ( phase III ) . RESULTS Seven PH patients in the phase III trial were identified as severe PH . Six of the patients were early onset ( occurred < 150 days of initiating bevacizumab ) and one was late onset . Baseline tumor cavitation , not tumor location , was identified as the only potential risk factor for patients with early onset . Combined analysis of severe PH patients from the phase II and phase III trials ( n = 13 ) , compared with their pooled matched controls ( n = 42 ) , did not identify any additional baseline radiographic or clinical variables associated with PH . CONCLUSION PH was an uncommon event . Based on these analyses , baseline tumor cavitation may be a potential risk factor for PH . No other baseline clinical variables were predictive for PH although the number of events was small Introduction : The combination of paclitaxel/carboplatin ( PC ) and bevacizumab ( B ) was previously shown to extend overall survival ( OS ) in patients with advanced nonsquamous non-small cell lung cancer ( NSCLC ) . An analysis of survival and safety outcomes based on histology is presented here . Methods : Patients with cytologically or histologically confirmed metastatic NSCLC were treated with PC + B ( PCB ) or PC . Median OS for all patients was determined using Kaplan-Meier methodology . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were obtained using an unstratified Cox proportional hazards model . Histology-by-treatment interaction was tested with an unstratified multivariate Cox regression model . Results : A total of 444 patients were r and omized to PC , and 434 patients were r and omized to PCB ( the intent-to-treat population ) . Median OS times were 10.3 and 12.3 months for PC and PCB , respectively , with an HR for PCB of 0.80 ( 95 % CI : 0.69 - 0.93 ) . A total of 68.8 % of patients had adenocarcinoma histology ; 18.9 % had “ not otherwise specified ” ; 5.5 % had large cell undifferentiated ; 2.6 % had bronchoalveolar carcinoma ; and 3.9 % “ other . ” For adenocarcinoma , median OS was 10.3 months for PC treatment ( n = 302 ) and 14.2 months for PCB ( n = 300 ) , HR 0.69 ( 95%CI : 0.58 - 0.83 ) . Sample sizes for other specific histologic subtypes were too small for meaningful comparisons . Safety profiles among histologies were consistent with the overall safety profile , and there were no unexpected adverse event trends . Conclusions : Addition of B to PC is associated with increased survival in previously untreated patients with nonsquamous NSCLC . Adenocarcinoma was associated with an increased survival benefit of PCB treatment . Data for other histologies are inconclusive , primarily because of small patient sample sizes and large CIs BACKGROUND Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy . We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy . METHODS We undertook an open-label phase III study with recruitment between March 1 , 2004 , and Feb 17 , 2006 , at 149 centres in 24 countries . 1466 patients with pretreated ( > /=one platinum-based regimen ) advanced non-small-cell lung cancer were r and omly assigned with dynamic balancing to receive gefitinib ( 250 mg per day orally ; n=733 ) or docetaxel ( 75 mg/m(2 ) intravenously in 1-h infusion every 3 weeks ; n=733 ) . The primary objective was to compare overall survival between the groups with co- primary analyses to assess non-inferiority in the overall per- protocol population and superiority in patients with high epidermal growth factor receptor (EGFR)-gene-copy number in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00076388 . FINDINGS 1433 patients were analysed per protocol ( 723 in gefitinib group and 710 in docetaxel group ) . Non-inferiority of gefitinib compared with docetaxel was confirmed for overall survival ( 593 vs 576 events ; hazard ratio [ HR ] 1.020 , 96 % CI 0.905 - 1.150 , meeting the predefined non-inferiority criterion ; median survival 7.6 vs 8.0 months ) . Superiority of gefitinib in patients with high EGFR-gene-copy number ( 85 vs 89 patients ) was not proven ( 72 vs 71 events ; HR 1.09 , 95 % CI 0.78 - 1.51 ; p=0.62 ; median survival 8.4 vs 7.5 months ) . In the gefitinib group , the most common adverse events were rash or acne ( 360 [ 49 % ] vs 73 [ 10 % ] ) and diarrhoea ( 255 [ 35 % ] vs 177 [ 25 % ] ) ; whereas in the docetaxel group , neutropenia ( 35 [ 5 % ] vs 514 [ 74 % ] ) , asthenic disorders ( 182 [ 25 % ] vs 334 [ 47 % ] ) , and alopecia ( 23 [ 3 % ] vs 254 [ 36 % ] ) were most common . INTERPRETATION INTEREST established non-inferior survival of gefitinib compared with docetaxel , suggesting that gefitinib is a valid treatment for pretreated patients with advanced non-small-cell lung cancer BACKGROUND First-line chemotherapy for advanced non-small-cell lung cancer ( NSCLC ) is usually limited to four to six cycles . Maintenance therapy can delay progression and prolong survival . The oral epidermal growth factor receptor ( EGFR ) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC . We design ed the phase 3 , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy . METHODS Between December , 2005 , and May , 2008 , 1949 patients were included in the run-in phase ( four cycles of platinum-based chemotherapy ) . At the end of the run-in phase , 889 patients who did not have progressive disease were entered into the main study , and were r and omly allocated using a 1:1 adaptive r and omisation method through a third-party interactive voice response system to receive erlotinib ( 150 mg/day ; n=438 ) or placebo ( n=451 ) until progression or unacceptable toxicity . Patients were stratified by EGFR immunohistochemistry status , stage , Eastern Cooperative Oncology Group performance status , chemotherapy regimen , smoking history , and region . Co- primary endpoints were progression-free survival ( PFS ) in all analysable patients irrespective of EGFR status , and PFS in patients whose tumours had EGFR protein overexpression , as determined by immunohistochemistry . This study is registered with www . Clinical Trials.gov , number NCT00556712 . FINDINGS 884 patients were analysable for PFS ; 437 in the erlotinib group and 447 in the placebo group . After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group , median PFS was significantly longer with erlotinib than with placebo : 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group ( HR 0.71 , 95 % CI 0.62 - 0.82 ; p<0.0001 ) . PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib ( n=307 ) compared with EGFR-positive patients given placebo ( n=311 ; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group ; HR 0.69 , 0.58 - 0.82 ; p<0.0001 ) . The most common grade 3 or higher adverse events were rash ( 37 [ 9 % ] of 443 patients in the erlotinib group vs none of 445 in the placebo group ) and diarrhoea ( seven [ 2 % ] of 443 patients vs none of 445 ) . Serious adverse events were reported in 47 patients ( 11 % ) on erlotinib compared with 34 patients ( 8 % ) on placebo . The most common serious adverse event was pneumonia ( seven cases [ 2 % ] with erlotinib and four [ < 1 % ] with placebo ) . INTERPRETATION Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo . First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy . FUNDING F Hoffmann-La Roche PURPOSE Bevacizumab , a monoclonal antibody targeting vascular endothelial growth factor , improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer ( NSCLC ) . This r and omized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine ( CG ) plus bevacizumab in this setting . PATIENTS AND METHODS Patients were r and omly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m(2 ) for up to six cycles plus low-dose bevacizumab ( 7.5 mg/kg ) , high-dose bevacizumab ( 15 mg/kg ) , or placebo every 3 weeks until disease progression . The trial was not powered to compare the two doses directly . The primary end point was amended from overall survival ( OS ) to progression-free survival ( PFS ) . Between February 2005 and August 2006 , 1,043 patients were r and omly assigned ( placebo , n = 347 ; low dose , n = 345 ; high dose , n = 351 ) . RESULTS PFS was significantly prolonged ; the hazard ratios for PFS were 0.75 ( median PFS , 6.7 v 6.1 months for placebo ; P = .003 ) in the low-dose group and 0.82 ( median PFS , 6.5 v 6.1 months for placebo ; P = .03 ) in the high-dose group compared with placebo . Objective response rates were 20.1 % , 34.1 % , and 30.4 % for placebo , low-dose bevacizumab , and high-dose bevacizumab plus CG , respectively . Duration of follow-up was not sufficient for OS analysis . Incidence of grade 3 or greater adverse events was similar across arms . Grade > or = 3 pulmonary hemorrhage rates were < or = 1.5 % for all arms despite 9 % of patients receiving therapeutic anticoagulation . CONCLUSION Combining bevacizumab ( 7.5 or 15 mg/kg ) with CG significantly improved PFS and objective response rate . Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC PURPOSE The anti-epidermal growth factor receptor ( EGFR ) antibody cetuximab is efficacious in multiple tumor types . Patient selection with markers predictive of benefit may enhance its therapeutic index . This retrospective , correlative analysis of the phase III trial BMS099 of cetuximab in advanced non-small-cell lung cancer ( NSCLC ) was conducted to identify molecular markers for the selection of patients most likely to benefit from cetuximab . METHODS In BMS099 , 676 chemotherapy-naïve patients with stage IIIB ( pleural effusion ) or stage IV NSCLC of any histology or EGFR expression status were r and omly assigned to taxane/carboplatin ( T/C ) with or without cetuximab . Biomarkers analyzed included K-Ras and EGFR mutations by direct sequencing , EGFR protein expression by immunohistochemistry ( IHC ) , and EGFR gene copy number by fluorescent in situ hybridization ( FISH ) . Relationships between biomarker status and progression-free survival ( PFS ) , overall survival ( OS ) , and overall response rate ( ORR ) were assessed by log-rank tests per treatment arm for treatment-specific effects and across the total evaluable population . Results Tumor sample s were available from 225 r and omly assigned patients . K-Ras mutations were found in 17 % of evaluable patients ( 35 of 202 patients ) , EGFR mutations were found in 10 % ( 17 of 166 patients ) , EGFR positivity by IHC was found in 89 % ( 131 of 148 patients ) , and FISH positivity was found in 52 % ( 54 of 104 patients ) . No significant associations were found between biomarker status and PFS , OS , and ORR in the treatment-specific analyses . CONCLUSION In contrast with colorectal cancer , and within the limitations of the data set , efficacy parameters did not appear to correlate with K-Ras mutation status or with any of the EGFR-related biomarkers evaluated . Additional exploratory analyses are essential to identify predictive markers and to optimize patient selection for cetuximab therapy in NSCLC Background : E4599 was a phase II/phase III trial , in which 878 patients with advanced non – small cell lung cancer were r and omized to carboplatin + paclitaxel ( PC arm ) or PC + bevacizumab ( BPC arm ) . Survival and progression-free survival were superior on the BPC arm . The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , soluble intercellular adhesion molecule ( ICAM ) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis . Material s and Methods : Prospect i ve correlates included measurements of pretreatment plasma VEGF , as well as pretreatment and week 7 , bFGF , ICAM , and E-selectin . Low and high levels were defined as less than or equal to or more than the median . Results : E-selectin ( P < 0.0001 ) showed a decrease and bFGF showed an increase ( P = 0.004 ) from baseline at week 7 , which were similar in both arms . Baseline ICAM showed significant associations with response and survival in both groups . Patients with low baseline ICAM had a higher response rate ( 32 % versus 14 % ; P = 0.02 ) , better overall survival ( P = 0.00005 ) , and better 1-year survival ( 65 % versus 25 % ) than those with high ICAM , respectively , regardless of treatment arm . Patients with high VEGF levels were more likely to respond to BPC compared with PC , but this was not predictive of survival . The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels ( 53 % reduction in the progression-free survival hazard rate ) . Conclusions : In this study , baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab . VEGF levels were predictive of response to bevacizumab but not survival |
11,248 | 30,209,002 | The pNETs trials consistently found that the interventions improved PFS and overall survival ( OS ) compared with BSC .
Our indirect comparison found no significant difference in PFS between everolimus and sunitinib .
After adjustment , our indirect comparison suggested a lower , but non-significant , hazard of death for sunitinib compared with everolimus .
In GI and lung NETs , everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC .
Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC .
Given NICE 's current stated range of £ 20,000 - 30,000 per QALY for the cost-effectiveness threshold , based on list prices , only sunitinib might be considered good value for money in Engl and and Wales . | BACKGROUND Neuroendocrine tumours ( NETs ) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system .
OBJECTIVES To estimate the clinical effectiveness of three interventions [ everolimus ( Afinitor ® ; Novartis International AG , Basel , Switzerl and ) , lutetium-177 DOTATATE ( 177Lu-DOTATATE ) ( Lutathera ® ; Imaging Equipment Ltd , Radstock , UK ) and sunitinib ( Sutent ® ; Pfizer Inc. , New York , NY , USA ) ] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions . | Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours . Treatment with the radiolabelled somatostatin analogue [90Y-DOTA0,Tyr3]octreotide may result in partial remissions in 10–25 % of patients . The newer analogue [DOTA0,Tyr3]octreotate ( octreotate ) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0,Tyr3]octreotide . Also , labelled with the beta- and gamma-emitting radionuclide 177Lu , it has proved very successful in achieving tumour regression in animal models . The effects of 177Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic ( GEP ) tumours who underwent follow-up for 3–6 months after receiving their final dose . Patients were treated with doses of 100 , 150 or 200 mCi 177Lu-octreotate , to a final cumulative dose of 600–800 mCi , with treatment intervals of 6–9 weeks . Nausea and vomiting within the first 24 h after administration were present in 30 % and 14 % of the administrations , respectively . WHO toxicity grade 3 anaemia , leucocytopenia and thrombocytopenia occurred after 0 % , 1 % and 1 % of the administrations , respectively . Serum creatinine and creatinine clearance did not change significantly . The effects of the therapy on tumour size were evaluable in 34 patients . Three months after the final administration , complete remission was found in one patient ( 3 % ) , partial remission in 12 ( 35 % ) , stable disease in 14 ( 41 % ) and progressive disease in seven ( 21 % ) , including three patients who died during the treatment period . Tumour response was positively correlated with a high uptake on the octreoscan , limited hepatic tumour mass and a high Karnofsky Performance Score . Because of the limited efficacy of alternative therapies , many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours . However , in view of the high success rate of therapy with 177Lu-octreotate and the absence of serious side-effects , we advocate its use in patients with GEP tumours without waiting for tumour progression Objective Everolimus , an inhibitor of the mammalian target of rapamycin , has recently demonstrated efficacy and safety in a Phase III , double-blind , r and omized trial ( RADIANT-3 ) in 410 patients with low- or intermediate- grade advanced pancreatic neuroendocrine tumours . Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival , representing a 65 % risk reduction for progression . The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study . Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally ( n = 23 ) and matching placebo ( n = 17 ) . The primary endpoint was progression-free survival . Safety was evaluated on the basis of the incidence of adverse drug reactions . Results Progression-free survival was significantly prolonged with everolimus compared with placebo . The median progression-free survival was 19.45 months ( 95 % confidence interval , 8.31–not available ) with everolimus vs 2.83 months ( 95 % confidence interval , 2.46–8.34 ) with placebo , result ing in an 81 % risk reduction in progression ( hazard ratio , 0.19 ; 95 % confidence interval , 0.08–0.48 ; P < 0.001 ) . Adverse drug reactions occurred in all 23 ( 100 % ) Japanese patients receiving everolimus and in 13 ( 77 % ) patients receiving placebo ; most were grade 1/2 in severity . The most common adverse drug reactions in the everolimus group were rash ( n = 20 ; 87 % ) , stomatitis ( n = 17 ; 74 % ) , infections ( n = 15 ; 65 % ) , nail disorders ( n = 12 ; 52 % ) , epistaxis ( n = 10 ; 44 % ) and pneumonitis ( n = 10 ; 44 % ) . Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours BACKGROUND Gastric carcinoid tumours type 1 ( GCA1 ) originate from hyperplastic enterochromaffin-like ( ECL ) cells secondary to hypergastrinaemia . Treatment with somatostatin analogues ( SSA ) might impede ECL-cell hyperplasia by suppressing gastrin secretion and /or by a direct anti-proliferative effect on ECL cells . We conducted a multicentre prospect i ve study to assess the effects of long-acting SSA on hypergastrinaemia and ECL-cell proliferation in patients with GCA1 . METHODS We studied 15 patients with GCA1 treated with monthly long-acting release octreotide ( LAR ) ( 20 - 30 mg ; n=14 ) or Lanreotide 90 mg ( n=1 ) for at least 6 months . Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from both tumours and surrounding mucosa before , and every 6 - 12 months following treatment . Sections were immunostained for neuroendocrine markers . The cell proliferation index Ki-67 , intensity of staining before and after treatment and the degree of gastric wall invasion were also assessed . RESULTS All patients tolerated treatment well ( mean follow-up of 18 months ) . In 11 patients ( 73 % ) , a complete disappearance of the tumours at 1 year of treatment was observed on endoscopy , while in three patients ( 20 % ) , the tumours decreased significantly in number and size . Gastrin levels normalized in 25 % of patients , and were reduced by more than 80 % in the remaining 75 % . CONCLUSIONS Treatment with SSAs in GCA1 leads to a substantial tumour load reduction , with a concomitant decrease of serum gastrin levels . Our data indicate an important anti-proliferative effect of SSA on ECL cells , providing clinical benefit and obviating , at least temporarily , the need for invasive therapies for GCA1 4008 Background : In a double-blind phase 3 trial , SU improved PFS vs PBO ( 11.4 vs 5.5 months ; HR 0.418 , 95 % CI 0.263 , 0.662 ; p=0.0001 ) and was well tolerated in pts with advanced well-differentiated , unresectable NET that had progressed in ≤12 months ( NEJM , Feb 2011 ) . Initial OS showed a benefit for SU over PBO , but median OS was not reached ( NR ) . Here we report up date d results of median OS and also PFS assessed by BICR to correct for potential unblinding due to identifiable adverse events ( AE ) . METHODS Pts were r and omized 1:1 to SU 37.5 mg as a continuous daily dose or PBO , each with best supportive care . Primary endpoint was PFS ; secondary endpoint was OS . Median OS and HR were estimated using Kaplan-Meier ( K-M ) methods and Cox proportional hazards models . Baseline and on- study CT/MRI scans were evaluated by a 2-reader , 2-time point lock , followed by a sequential locked-read , batch-mode paradigm by blinded , third-party radiologists . RESULTS 171 pts were r and omized ( SU , n=86 ; PBO , n=85 ) from 6/2007 to 4/2009 . The trial ended early when an independent data monitoring committee noted efficacy favoring SU and more serious AEs and deaths with PBO . The study was unblinded at closure , and pts were offered open-label SU . At study end , there were 9 and 21 deaths in SU and PBO arms , respectively ; HR of 0.409 ( 95 % CI 0.187 , 0.894 ; p=0.0204 ) favoring SU . By 6/2010 , there were 34 and 39 deaths , respectively ; median OS was 30.5 ( 95 % CI 20.6 , NR ) and 24.4 ( 95 % CI : 16.3 , NR ) months , respectively . The HR of 0.737 ( 95 % CI 0.465 , 1.168 ; p=0.1926 ) continued to favor SU ; a K-M plot showed early/persistent separation of curves . For BICR analysis , scans were collected for 170 ( 99.4 % ) pts , with 160 ( 93.6 % ) having complete scan sets/time points . Median PFS by BICR was 12.6 vs 5.8 months for SU and PBO ( HR 0.315 [ 95 % CI 0.181 , 0.546 ; p=0.000015 ] ) . CONCLUSIONS SU led to a 6.1-month improvement in median OS vs PBO , and BICR analysis confirmed the investigator-assessed PFS benefit of SU . These up date d results support the robustness of the initial findings and the clinical benefit of treatment with sunitinib PURPOSE Effective systemic therapy for advanced carcinoid is lacking . The combination of bevacizumab ( BEV ) and pegylated ( PEG ) interferon alpha-2b was evaluated among patients with metastatic or unresectable carcinoid tumors . PATIENTS AND METHODS Forty-four patients on stable doses of octreotide were r and omly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alpha-2b . At disease progression ( PD ) or at the end of 18 weeks ( whichever occurred earlier ) , patients received bevacizumab plus PEG interferon until progression . Functional computer tomography ( CT ) scans were performed to measure effect on tumor blood flow . RESULTS In the bevacizumab arm , four patients ( 18 % ) achieved confirmed partial response ( PR ) , 17 patients ( 77 % ) had stable disease ( SD ) , and one patient ( 5 % ) had PD . In the PEG interferon arm , 15 patients ( 68 % ) had SD and six patients ( 27 % ) had PD . Progression-free survival ( PFS ) rates after 18 weeks of monotherapy were 95 % in bevacizumab versus 68 % on the PEG interferon arm . The overall median PFS for all 44 patients is 63 weeks . Compared with paired baseline measurements on functional CT scans , we observed a 49 % ( P < .01 ) and 28 % ( P < .01 ) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab . No significant changes in tumor blood flow were observed following PEG interferon . PEG interferon alpha-2b treatment was associated with decrease in plasma basic fibroblast growth factor ( bFGF ; P = .04 ) and increase in plasma interleukin-18 ( IL-18 ; P < .01 ) . No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed . CONCLUSION Bevacizumab therapy result ed in objective responses , reduction of tumor blood flow , and longer PFS in patients with carcinoid than PEG interferon treatment PURPOSE Optimal treatments for metastatic carcinoid tumor remain undefined , and the role of chemotherapy for symptomatic patients with progressive disease is uncertain . PATIENTS AND METHODS Two hundred forty-nine patients with advanced carcinoid tumors were r and omized to either doxorubicin with fluorouracil ( FU/DOX ) or streptozocin with fluorouracil ( FU/STZ ) . Patients crossed over to the dacarbazine ( DTIC ) treatment after disease progression following first-line treatment ( either FU/DOX or FU/STZ ) , and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function . RESULTS In the r and omized group , there was no difference between FU/DOX and FU/STZ in response rates ( 15.9 % v 16 % ) and progression-free survival ( 4.5 v 5.3 months ) . FU/STZ ( 24.3 months ) was superior to FU/DOX ( 15.7 months ; P = .0267 ) in median survival . The response rate of crossover DTIC treatment was 8.2 % , with a median survival of 11.9 months . Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ , and mild to moderate renal toxicity was reported in 40 ( 34.8 % ) of 115 patients in the FU/STZ arm . CONCLUSION Response to all three treatment regimens were modest . FU/STZ improved survival compared with the doxorubicin-based regimen , suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors These guidelines up date previous guidance published in 2005 . They have been revised by a group who are members of the UK and Irel and Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology , the Society for Endocrinology , the Association of Surgeons of Great Britain and Irel and ( and its Surgical Specialty Associations ) , the British Society of Gastrointestinal and Abdominal Radiology and others . The authors hip represents leaders of the various groups in the UK and Irel and Neuroendocrine Tumour Society , but a large amount of work has been carried out by other specialists , many of whom attended a guidelines conference in May 2009 . We have attempted to represent this work in the acknowledgements section . Over the past few years , there have been advances in the management of neuroendocrine tumours , which have included clearer characterisation , more specific and therapeutically relevant diagnosis , and improved treatments . However , there remain few r and omised trials in the field and the disease is uncommon , hence all evidence must be considered weak in comparison with other more common cancers . Background Everolimus and sunitinib have been approved for the treatment advanced pancreatic neuroendocrine tumors , but have not been compared to each other in a r and omized trial and have not demonstrated prolonged overall survival compared to placebo . This study aim ed to indirectly compare overall and progression-free among everolimus , sunitinib and placebo across separate r and omized trials . Methods A matching adjusted indirect comparison was conducted in which individual patient data from the pivotal trial of everolimus ( n = 410 ) were adjusted to match the inclusion criteria and average baseline characteristics reported for the pivotal trial of sunitinib ( n = 171 ) . Prior to matching , trial population s differed in baseline performance status and prior treatments . After matching , these and all other available baseline characteristics were balanced between trials . Results Compared to the placebo arm in the sunitinib trial , everolimus was associated with significantly prolonged overall survival ( HR = 0.61 , 95 % CI = 0.38 - 0.98 , p = 0.042).Compared to sunitinib , everolimus was associated with similar progression-free ( hazard ratio for death ( HR ) = 0.84 , 95 % CI = 0.46–1.53 , p = 0.578 ) and overall survival ( HR = 0.81 , 95 % CI = 0.49–1.31 , p = 0.383 ) . Conclusion After adjusting for observed cross-trial differences , everolimus treatment was associated with longer overall survival than the placebo arm in the sunitinib trial for advanced pancreatic neuroendocrine tumors BACKGROUND The incidence of neuroendocrine tumors ( NETs ) has increased approximately fivefold since the 1980s . A similar increase in the incidence of lung NETs has been reported , but therapy has not been optimized . METHODS This exploratory sub analysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable ( LAR ) in a cohort of patients with low- to intermediate- grade advanced lung NET from the phase 3 , r and omized , placebo-controlled RADIANT-2 ( RAD001 in Advanced Neuroendocrine Tumors ) study . The primary end point was progression-free survival ( PFS ) . Secondary end points included objective response rate , overall survival , change from baseline in biomarker levels , and safety outcomes . RESULTS Patients were r and omly assigned to everolimus plus octreotide LAR ( n 5 33 ) or placebo plus octreotide LAR ( n 5 11 ) . Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm ( relative risk for progression : HR , 0.72 ; 95 % CI , 0.31–1.68 ; P 5 .228 ) . More patients receiving everolimus plus octreotide LAR ( 67 % ) experienced minor tumor shrinkage ( not partial response as per RECIST [ Response Evaluation Criteria in Solid Tumors ] ) than those receiving placebo plus octreotide LAR ( 27 % ) . Most frequently reported adverse events ( AEs ) included stomatitis , rash , diarrhea , and asthenia . This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus . CONCLUSIONS This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET , the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR . These clinical ly significant observations support the continued evaluation of everolimus treatment regimens in this patient population . TRIAL REGISTRY Clinical Trials.gov ; No. : Background / Aims An open-label , multi-center , exp and ed access study was conducted in patients with advanced neuroendocrine tumors ( NET ) treated with everolimus ( 10 mg/day ) to assess safety and health-related quality of life ( HRQOL ) . Methods Of the 246 patients enrolled , 126 have pancreatic NET ( pNET ) and 120 have non-pNET . Patients continued treatment until disease progression , unacceptable toxicity , death , until commercial availability of everolimus , or May 2012 , whichever came first . Adverse events ( AEs ) were analyzed according to Common Terminology Criteria version 4.0 . HRQOL was assessed at baseline , for three 28-day cycles , and then at every three cycles until end of treatment ( EOT ) with EQ-5D , EORTC QLQ-C30 , and EORTC QLQ-GINET21 instruments . Results The most common grade 3 or 4 AEs included hyperglycemia , infections , stomatitis , fatigue , and abdominal pain . In patients with pNET , mean ( ± SD ) EQ VAS score remained stable at EOT ( baseline , 68.8 ± 19.9 vs. EOT , 66.5 ± 20.6 ) without clinical ly significant change in QLQ-C30 global health status ( change from baseline , - 3.9 ; n = 86 ) . For patients with non-pNET , a reduction in EQ VAS score ( 63.9 ± 19.0 vs. 55.3 ± 23.0 ) with clinical ly significant changes in QLQ-C30 global health status ( -13.0 ; n = 69 ) was seen by EOT . EQ-5D utility scores remained stable in patients with pNET and a moderate decrease was reported by patients with non-pNET . Conclusions The safety profile of everolimus was consistent with the previous studies without adversely affecting HRQOL in pNET . Lower baseline HRQOL scores and more frequent comorbidities might have contributed to the worse outcomes in non-pNET.Trial Registration EudraCT no. 2010 - 023032 - Purpose The clinical benefit of peptide receptor radionuclide therapy ( PRRT ) in patients with pancreatic neuroendocrine tumours ( pNET ) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup . This study was intended to obtain robust , comparative data on the outcome and toxicity of st and ardized PRRT with 177Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 ( G1/2 ) . Methods We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with 177Lu-octreotate ( four intended cycles at 3-monthly intervals ; mean activity per cycle 8.0 GBq ) . Of these 68 patients , 46 ( 67.6 % ) had documented morphological tumour progression during the 12 months before initiation of treatment , and PRRT was the first-line systemic therapy in 35 patients ( 51.5 % ) . Response was evaluated according to modified Southwest Oncology Group ( SWOG ) criteria and additionally with Response Criteria in Solid Tumors ( RECIST ) 1.1 . Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses . Toxicity was assessed by st and ard follow-up laboratory work-up including blood count , and liver and renal function , supplemented with serial 99mTc-DTPA clearance measurements . Results The median follow-up period was 58 months ( range 4 – 112 ) . Reversible haematotoxicity ( grade 3 or more ) occurred in four patients ( 5.9 % ) . No significant nephrotoxicity ( grade 3 or more ) was observed . Treatment responses ( SWOG criteria ) consisted of a partial response in 41 patients ( 60.3 % ) , a minor response in 8 ( 11.8 % ) , stable disease in 9 ( 13.2 % ) , and progressive disease in 10 ( 14.7 % ) . Median progression-free survival ( PFS ) and overall survival ( OS ) were 34 ( 95 % CI 26 – 42 ) and 53 months ( 95 % CI 46 – 60 ) , respectively . A G1 proliferation status was associated with longer PFS ( p = 0.04 ) and OS ( p = 0.044 ) in the multivariate analysis . Variables linked to impaired OS , on the other h and , were a reduced performance status ( Karnofsky score ≤70 % , p = 0.007 ) , a high hepatic tumour burden ( ≥25 % liver volume , p = 0.017 ) , and an elevated plasma level of neuron-specific enolase ( NSE > 15 ng/ml , p = 0.035 ) . Conclusion The outst and ing response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities . Independent predictors of survival are the tumour proliferation index , the patient ’s performance status , tumour burden and baseline plasma NSE level BACKGROUND The combination of streptozocin and fluorouracil has become the st and ard therapy for advanced islet-cell carcinoma . However , doxorubicin has also been shown to be active against this type of tumor , as has chlorozotocin , a drug that is structurally similar to streptozocin but less frequently causes vomiting . METHODS In this multicenter trial , we r and omly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens : streptozocin plus fluorouracil , streptozocin plus doxorubicin , or chlorozotocin alone . The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens . RESULTS Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression , measured objective ly ( 69 percent vs. 45 percent , P = 0.05 ) , and the length of time to tumor progression ( median , 20 vs. 6.9 months ; P = 0.001 ) . Streptozocin plus doxorubicin also had a significant advantage in terms of survival ( median , 2.2 vs. 1.4 years ; P = 0.004 ) that was accentuated when we considered long-term survival ( greater than 2 years ) . Chlorozotocin alone produced a 30 percent regression rate , with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil . Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent , and the responses were transient . Toxic reactions to all regimens included vomiting , which was least severe with chlorozotocin ; hematologic depression ; and , with long-term therapy , renal insufficiency . CONCLUSIONS The combination of streptozocin and doxorubicin is superior to the current st and ard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma . Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil , but it produces fewer gastrointestinal side effects than the regimens containing streptozocin . It therefore merits study as a constituent of combination drug regimens Purpose In this phase II study we investigated the safety and efficacy of combination capecitabine and 177Lu-octreotate for the treatment of disseminated , progressive , unresectable neuroendocrine tumours ( NETs ) . Methods Enrolled in the study were 33 patients with biopsy-proven NETs , positive 111In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq 177Lu-octreotate 8-weekly , with 14 days of 1,650 mg/m2 capecitabine per day . Results Of the 33 patients , 25 completed four cycles . Minimal transient myelosuppression at 3–4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia . Nephrotoxicity was absent . Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy , and showed cumulative doses all below toxic thresholds . Objective response rates ( ORR ) were 24 % partial response ( PR ) , 70 % stable disease ( SD ) and 6 % progressive disease . Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months ( range 5–33 months ) . Survival at 1 and 2 years was 91 % ( 95 % CI 75–98 % ) and 88 % ( 95 % CI 71–96 % ) , respectively . Conclusion The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of 177Lu-octreotate radiopeptide therapy and led to an ORR of 24 % PR and 70 % minor response or SD in patients with progressive metastatic NETs . Tumour control and stabilization of disease was obtained in 94 % of these patients BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of 302 patients were enrolled , of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo . Median progression-free survival was 11·0 months ( 95 % CI 9·2 - 13·3 ) in the everolimus group and 3·9 months ( 3·6 - 7·4 ) in the placebo group . Everolimus was associated with a 52 % reduction in the estimated risk of progression or death ( hazard ratio [ HR ] 0·48 [ 95 % CI 0·35 - 0·67 ] , p<0·00001 ) . Although not statistically significant , the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death ( HR 0·64 [ 95 % CI 0·40 - 1·05 ] , one-sided p=0·037 , whereas the boundary for statistical significance was 0·0002 ) . Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis ( in 18 [ 9 % ] of 202 patients in the everolimus group vs 0 of 98 in the placebo group ) , diarrhoea ( 15 [ 7 % ] vs 2 [ 2 % ] ) , infections ( 14 [ 7 % ] vs 0 ) , anaemia ( 8 [ 4 % ] vs 1 [ 1 % ] ) , fatigue ( 7 [ 3 % ] vs 1 [ 1 % ] ) , and hyperglycaemia ( 7 [ 3 % ] vs 0 ) . INTERPRETATION Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours . The safety findings were consistent with the known side-effect profile of everolimus . Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours , including those arising from the pancreas , lung , and gastrointestinal tract . FUNDING Novartis Pharmaceuticals Corporation Purpose Peptide receptor radionuclide therapy ( PRRT ) is used in tumours expressing type 2 somatostatin receptors ( sst2 ) , mainly neuroendocrine . The aim of this prospect i ve phase I-II study was to evaluate the toxicity and efficacy of 177Lu-DOTATATE in multiple cycles . Methods Fifty-one consecutive patients with unresectable/metastatic sst2-positive tumours , divided into two groups , received escalating activities ( 3.7–5.18 GBq/cycle , group 1 ; 5.18–7.4 GBq/cycle , group 2 ) of 177Lu-DOTATATE . Cumulative activities ranged from 3.7 to 29.2 GBq ( median 26.4 GBq in median 6 cycles , group 1 , 21 patients ) and 5.55 to 28.9 GBq ( median 25.2 GBq in 4 cycles , group 2 , 30 patients ) , based on dosimetry . Results No major acute or delayed renal or haematological toxicity occurred ( one grade 3 leukopenia and thrombocytopenia ) . Cumulative renal absorbed doses were 8–37 Gy ( 9–41 Gy bioeffective doses ) . A median decrease of creatinine clearance of 21.7 % 6 months after PRRT , 23.9 % after 1 year and 27.6 % after 2 years was observed . Higher losses ( > 20 % ) occurred in patients with risk factors for renal toxicity , particularly hypertension and diabetes . Cumulative bone marrow doses were < 1.5 Gy . Blood elements showed a progressive mild drop during cycles and recovered during follow-up ( median 30 months ) . Thirty-nine patients were progressive at enrolment . Partial and complete responses occurred in 15 of 46 ( 32.6 % ) assessable patients . The median time to progression was 36 months . Overall survival was 68 % at 36 months . Non-responders and patients with extensive tumour involvement had lower survival . Conclusion 177Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity ( up to 7.4 GBq/cycle ) . The maximum tolerated dose/cycle was not reached . However , considering the individual bone marrow function and the presence of risk factors for kidney toxicity , it seems safer to divide cumulative activities into lower activity cycles Background The results of R and omized Controlled Trials ( RCTs ) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio . These do not constitute the sufficient statistics required for meta- analysis or cost-effectiveness analysis , and their use in secondary analyses requires strong assumptions that may not have been adequately tested . In order to enhance the quality of secondary data analyses , we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated . Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations , using where available information on number of events and numbers at risk . The reproducibility and accuracy of survival probabilities , median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics ( survival probabilities , medians and hazard ratios ) with statistics based on repeated reconstructions by multiple observers . Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics . Accuracy was excellent for survival probabilities and medians , for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported . Conclusion The algorithm is a reliable tool for meta- analysis and cost-effectiveness analyses of RCTs reporting time-to-event data . It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves Propensity score methods are increasingly being used to estimate causal treatment effects in observational studies . In medical and epidemiological studies , outcomes are frequently time-to-event in nature . Propensity-score methods are often applied incorrectly when estimating the effect of treatment on time-to-event outcomes . This article describes how two different propensity score methods ( matching and inverse probability of treatment weighting ) can be used to estimate the measures of effect that are frequently reported in r and omized controlled trials : ( i ) marginal survival curves , which describe survival in the population if all subjects were treated or if all subjects were untreated ; and ( ii ) marginal hazard ratios . The use of these propensity score methods allows one to replicate the measures of effect that are commonly reported in r and omized controlled trials with time-to-event outcomes : both absolute and relative reductions in the probability of an event occurring can be determined . We also provide guidance on variable selection for the propensity score model , highlight methods for assessing the balance of baseline covariates between treated and untreated subjects , and describe the implementation of a sensitivity analysis to assess the effect of unmeasured confounding variables on the estimated treatment effect when outcomes are time-to-event in nature . The methods in the paper are illustrated by estimating the effect of discharge statin prescribing on the risk of death in a sample of patients hospitalized with acute myocardial infa rct ion . In this tutorial article , we describe and illustrate all the steps necessary to conduct a comprehensive analysis of the effect of treatment on time-to-event outcomes . © 2013 The authors . Statistics in Medicine published by John Wiley & Sons , Introduction : Recent discoveries in cancer research have revealed a plethora of clinical ly actionable mutations that provide therapeutic , prognostic and predictive benefit to patients . The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing ( MPS ) of tumours in the general population is required to assess its value towards the health-care system . Methods : Cancer 2015 study is a large-scale , prospect i ve , multisite cohort of newly diagnosed cancer patients from Victoria , Australia with 1094 patients recruited . MPS was performed using the Illumina TruSeq Amplicon Cancer Panel . Results : Overall , 854 patients were successfully sequenced for 48 common cancer genes . Accurate determination of clinical ly relevant mutations was possible including in less characterised cancer types ; however , technical limitations including formalin-induced sequencing artefacts were uncovered . Applying strict filtering criteria , clinical ly relevant mutations were identified in 63 % of patients , with 26 % of patients displaying a mutation with therapeutic implication s. A subset of patients was vali date d for canonical mutations using the Agena Bioscience MassARRAY system with 100 % concordance . Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams ( breast carcinoma and colorectal adenocarcinoma ) , others were different ( lung adenocarcinoma and head and neck squamous cell carcinoma ) , which has significant implication s for health economic modelling of particular targeted agents . Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified . Conclusions : Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved , opening unexpected avenues for investigation and treatment of cancer patients Purpose We evaluated the activity and safety profile of 177Lu-Dotatate peptide receptor radionuclide therapy ( Lu-PRRT ) in patients with advanced , well-differentiated ( G1-G2 ) gastrointestinal neuroendocrine tumors ( GI-NETs ) . Methods Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan ® completed the treatment with Lu-PRRT , result ing in the cumulative activity of 18.5 or 27.8 GBq in five cycles . Total activity was scheduled on the basis of kidney function or bone marrow reserve . Results Twenty-five ( 58 % ) patients were treated with a “ st and ard ” Lu-PRRT full dosage ( FD ) of 25.7 GBq ( range 22.2 - 27.8 ) , while the remaining 18 patients ( 42 % ) who , at enrolment , showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage ( RD ) of 18.4 GBq ( range 14.4 - 20.4 ) . According to SWOG criteria , the overall response was complete response ( CR ) in ( 7 % ) cases and stable disease ( SD ) in 33 ( 77 % ) , with a disease control rate ( DCR ) of 84 % . Median response duration was 25 months ( range 7 - 50 ) . Median progression-free survival ( PFS ) was 36 months ( 95 % CI 24-nr ) , and median overall survival ( OS ) has not yet been reached . Remarkably , none of the patients , including those at a higher risk of toxicity , showed side-effects after either dosage of Lu-PRRT . Conclusion Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs , showing an 84 % DCR ( 95 % CI 73 - 95 ) that lasted for 25 months and a PFS of 36 months . Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients , including those with a higher probability of developing kidney or bone marrow toxicity Everolimus , an oral inhibitor of mammalian target of mTOR , has been recently shown to have antitumor effect in a phase III , double-blind , r and omized trial ( RADIANT-3 ) of 410 patients with advanced pancreatic neuroendocrine tumors ( PNETs ) . The purpose of this study was to investigate the specific efficacy and safety of everolimus in the Chinese patient with PNETs . In this r and omized phase II study , the analysis on Chinese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally ( n = 44 ) and matching placebo ( n = 35 ) . The primary endpoint was progression-free survival ( PFS ) . Adverse events were also examined . The median PFS was 15.47 months with everolimus [ 95 % confidence interval ( CI ) 10.52–26.37 ] , as compared to 4.29 months with placebo ( 95 % CI 2.22–10.75 ) , representing a 72 % reduction in the risk of progression or death ( hazard ratio 0.27 ; 95 % CI 0.13–0.59 ; P < 0.001 ) . Drug-associated adverse events ( AEs ) were mostly grade 1 or 2 , observed in all 44 ( 100 % ) patients receiving everolimus and in 29 ( 83 % ) patients receiving placebo . The most common AEs ( grade 1–4 ) associated with everolimus were rash ( n = 38 ; 86 % ) , stomatitis ( n = 30 ; 68 % ) , infections ( n = 33 ; 75 % ) , epistaxis ( n = 32 ; 73 % ) , pneumonitis ( n = 27 ; 61 % ) and anemia ( n = 22 ; 50 % ) . Everolimus when compared with placebo is effectively in improving PFS in Chinese patients with PNETs Pre clinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors . The activity and safety of everolimus was assessed in combination with octreotide long‐acting repeatable ( LAR ) in patients with neuroendocrine tumors ( NETs ) of gastroenteropancreatic and lung origin OBJECTIVES To compare the effect of octreotide with f placebo on symptoms , tumour marker and quality of life in patients with gastrointestinal neuroendocrine tumours and liver metastases . DESIGN A blinded , placebo-controlled , cross-over study was performed . The number of flushing epidodes and diarrhoea episodes were registered for 1 week prior to the study and for the 8-week duration of the study . Quality of life and 24-h urinary 5-hydroxyindoleacetic acid ( 5-HIAA ) excretion were measured before the start , and at 4 and 8 weeks . Quality of life was registered with the Psychosocial Adjustment to Illness Scale ( PAIS ) and 5-HIAA measured by high-performance chromatography with electrochemical detection . 5-HIAA values exceeding 45 mumol 24 h-1 were considered to be elevated . SETTING The study was performed in a tertiary referral centre . SUBJECTS Twelve patients were approached ; eleven patients were included , with a mean age of 56.5 ( range 30 - 72 ) years . The primary tumour originated from the small intestine in nine and from the pancreas in two patients . The main symptoms were diarrhoea , flushing and nausea . The 24-h excretion of 5-HIAA was increased in all patients . INTERVENTIONS Patients were treated for 4 weeks with octreotide ( 100 micrograms ) subcutaneously , twice daily , and for 4 weeks on placebo ( octreotide vehicle ) in r and om starting order . MAIN OUTCOME MEASURES The main outcome measures were the number of episodes of the main clinical symptom(s ) and 24-h 5-HIAA excretion . RESULTS Octreotide lowered diarrhoea and flushing frequency significantly compared to placebo . 5-HIAA excretion was reduced during treatment with the active drug . Two domains of the PAIS were significantly improved , indicating that the reduction of tumour marker and symptoms were clinical ly important . CONCLUSIONS The clinical effect of octreotide on symptoms in patients with neuroendocrine tumours was demonstrated in a controlled , prospect i ve trial BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) 289 Background : Everolimus demonstrated a statistically and clinical ly significant improvement in PFS over placebo in a multi-national , r and omized , placebo-controlled , phase III trial in patients with advanced low- or intermediate- grade pNET with disease progression within the prior 12 months ( RADIANT-3 ) ( Ann Oncol [ 2010 ] 21[suppl 6 ] : NP doi:10.1093/annonc/mdq340 ) . Forty patients were enrolled from Japanese sites and r and omized ( n=23 : everolimus ; n=17 : placebo ) in that study . The purpose of this report is to investigate the efficacy and safety in the Japanese subgroup . METHODS Subgroup analysis for the Japanese patients was performed comparing the efficacy and safety between everolimus 10mg/d orally plus best supportive care ( BSC ) and matching placebo plus BSC . The primary efficacy endpoint was progression-free survival ( PFS ) . The safety was evaluated based on the incidence of adverse events ( AEs ) . RESULTS Treatment with everolimus result ed in a significant prolongation by 16.62 months in median PFS ( 19.45 months for everolimus , 2.83 months for placebo ) , with 81 % reduction in the hazard ratio of progression/death ( HR 0.19 [ 95 % CI : 0.08 , 0.48 ] ; one-sided unstratified log-rank test : p<.001 ) . The most common AE was stomatitis ( 73.9 % everolimus vs 23.5 % placebo ) ; mostly grade 1/2 . Grade 3/4 AEs occurred in 69.5 % of the everolimus arm and 29.4 % of the placebo arm , and amongst the most frequent included ( % in everolimus vs % in placebo ) : neutropenia ( 17.4 % vs 3 % ) ; anemia ( 8.7 % vs 0 % ) ; pneumonitis ( 8.7 % vs 0 % ) ; leukopenia ( 8.7 % vs 0 % ) . The remainder of grade 3/4 AEs was less than 3 % . Median duration of exposure to everolimus was 57 weeks vs 47 weeks on placebo . Treatment discontinuation for AEs was 17 % in the everolimus arm vs 0 % in the placebo arm . CONCLUSIONS Everolimus demonstrated a clinical ly meaningful improvement in PFS over placebo in Japanese patients . Everolimus was well tolerated in Japanese patients , and no new safety concerns were noted . This result suggests that everolimus can be a st and ard treatment for Japanese patients with advanced pNET . [ Table : see text ] Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors ( NET ) compared with placebo in the RADIANT-3 study . Here , we present the final overall survival ( OS ) data and data on the impact of biomarkers on OS from the RADIANT-3 study . Methods Patients with advanced , progressive , low- or intermediate- grade pancreatic NET were r and omly assigned to everolimus 10 mg/day ( n = 207 ) or placebo ( n = 203 ) . Crossover from placebo to open-label everolimus was allowed on disease progression . Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator 's discretion ( extension phase ) . OS analysis was performed using a stratified log-rank test in the intent-to-treat population . The baseline levels of chromogranin A , neuron-specific enolase , and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored . Results Of 410 patients who were enrolled between July 2007 and March 2014 , 225 received open-label everolimus , including 172 patients ( 85 % ) r and omly assigned initially to the placebo arm . Median OS was 44.0 months ( 95 % CI , 35.6 to 51.8 months ) for those r and omly assigned to everolimus and 37.7 months ( 95 % CI , 29.1 to 45.8 months ) for those r and omly assigned to placebo ( hazard ratio , 0.94 ; 95 % CI , 0.73 to 1.20 ; P = .30 ) . Elevated baseline chromogranin A , neuron-specific enolase , placental growth factor , and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS . The most common adverse events included stomatitis , rash , and diarrhea . Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced , progressive pancreatic NET , the longest OS reported in a phase III study for this population . Everolimus was associated with a survival benefit of 6.3 months , although this finding was not statistically significant . Crossover of patients likely confounded the OS results Abstract We conducted a phase I-II clinical trial to assess the safety and efficacy of combining lutetium-177 ( (177)Lu)-octreotate with capecitabine and temozolomide in treating advanced low- grade neuroendocrine tumors ( NETs ) . All 35 patients received fixed activities of 7.8 GBq (177)Lu-octreotate each 8 weeks , with 14 days of capecitabine 1500 mg/m(2 ) for 4 cycles . In phase I , successive cohorts of patients received escalating doses of temozolomide in groupings of 100 , 150 , and 200 mg/m(2 ) in the last 5 days of each capecitabine cycle . In phase II , patients were treated with 200 mg/m(2 ) temozolomide . Treatment was well tolerated in all dosage groups . No dose-limiting grade 2 , 3 , or 4 toxicities were seen in cohorts 1 ( 100 mg/m(2 ) ) or 2 ( 150 mg/m(2 ) ) . Twenty-eight patients completed treatment at the 200 mg/m(2 ) temozolomide level . Adverse events were mild to moderate . The commonest toxicities were transient nausea grade 2 ( 18 % ) , grade 3 ( 3 % ) , thrombocytopenia grade 2 ( 24 % ) , and neutropenia grade 3 ( 6 % ) . There were no grade 4 events . Thirty-four patients were evaluable for tumor response . Overall , complete response ( CR ) was achieved in 15 % ( 95 % CI 3 - 27 ) ; partial response ( PR ) , in 38 % ( 95 % CI 22 - 55 ) ; stable disease ( SD ) , in 38 % ( 95 % CI 22 - 55 ) ; and 3 patients failed to respond to treatment . Median progression free survival ( PFS ) was 31 months ( 95 % CI 21 - 33 ) , and median overall survival ( OS ) has not been reached with 90 % surviving at 24 months follow-up ( range 21 - 30 ) . Overall objective response rate ( ORR ) in patients with gastroenteropancreatic NETs showed CR 16 % ( 95 % CI 3 - 28 ) , PR 41 % ( 95 % CI 24 - 58 ) , SD 37 % ( 95 % CI 21 - 54 ) , and PD 6 % ( 95 % CI 0 - 15 ) . Response rates were higher in patients with gastropancreatic NETs than in those with bowel primaries ( enteric-NETs ) ; CR 18 % versus 13 % , PR 64 % versus 13 % , SD 12 % versus 67 % . (177)Lu-octreotate , in combination with capecitabine and temozolomide , is well tolerated in patients with advanced low- grade NETs , and shows substantial tumor control rates 4009 Background : In the RADIANT-3 trial , everolimus , an oral inhibitor of mTOR , significantly prolonged progression-free survival ( PFS ) in pts with advanced pNET ( ESMO 2010 , Abstract # LBA9 ) . Up date d safety and exploratory biomarker analyses from this trial are presented . METHODS Pts with progressive , advanced low- or intermediate- grade pNET were r and omized to everolimus 10 mg/d orally ( n=207 ) or placebo ( n=203 ) ; both arms received best supportive care . The primary endpoint was PFS ( RECIST v1.0 ) . RESULTS Median PFS by investigator assessment with everolimus was 11.0 mo vs with 4.6 mo with placebo ( HR=0.35 ; 95 % CI , 0.27 - 0.45 ; p<0.0001 ) , result ing in a 65 % reduction in the risk for progression . Everolimus compared with placebo result ed in a rapid and significant ( p<0.001 ) reduction in baseline biomarkers , including chromogranin A , neuron-specific enolase , gastrin , and glucagon . Treatment arms were well balanced with respect to on- study somatostatin analog ( SSA ) use ( 39 % , everolimus arm ; 40 % , placebo arm ) . An improvement in median PFS was observed with everolimus vs placebo in pts who received on- study SSA ( 11.4 mo vs 3.9 mo ; HR=0.40 ; 95 % CI , 0.29 - 0.56 ) and those without on- study SSA ( 10.8 mo vs 4.6 mo ; HR=0.35 ; 95 % CI , 0.24 - 0.50 ) . Median safety follow-up is now 20.1 mo . Most common drug-related adverse events ( AEs ) with everolimus vs placebo were stomatitis ( 52.9 % vs 12.3 % ) , rash ( 48.5 % vs 10.3 % ) , diarrhea ( 34.3 % vs 10.3 % ) , and fatigue ( 32.4 % vs 14.3 % ) . The most common grade 3 - 4 AEs were anemia ( 5.9 % vs 0 % ) , hyperglycemia ( 5.9 % vs 2.5 % ) , stomatitis ( 4.9 % vs 0 % ) , and thrombocytopenia ( 3.9 % vs 0 % ) . CONCLUSIONS In the RADIANT-3 trial , the largest r and omized controlled trial ever completed in pts with progressive advanced pNET , everolimus provided a significant increase in median PFS , irrespective of SSA use , and significant reductions in tumor and secretory biomarkers . Oral stomatitis represented the most common drug-related AE ; however , grade 3 - 4 somatitis was rare . These emerging data , including longer follow-up safety data , support the use of everolimus as a st and ard of care for pts with progressive , advanced pNET Background There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors ( GEP-NETs ) in Japan . Methods We examined the epidemiology of GEP-NETs [ pancreatic endocrine tumors ( PETs ) and gastrointestinal neuroendocrine tumors ( GI-NETs ) ] in Japan in 2005 using a nationwide stratified r and om sampling method . Results A total of 2,845 individuals received treatment for PETs . Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000 . Non-functioning tumor (NF)-PET constituted 47.4 % , followed by insulinoma ( 38.2 % ) and gastrinoma ( 7.9 % ) . Distant metastases were reported in 21 % patients with NF-PETs and occurred more frequently as tumor size increased ( > 2 cm ) . Multiple endocrine neoplasia type 1 ( MEN-1 ) was detected in 10 % of PETs but only in 6.1 % of NF-PETs . NF-PETs were detected incidentally by physical examination in 24 % patients . In 2005 , an estimated 4,406 patients received treatment for GI-NETs . Prevalence was estimated as 3.45/100,000 , with an annual onset incidence of 2.10/100,000 . The locations of GI-NETs varied : foregut , 30.4 % ; midgut , 9.6 % ; and hindgut , 60.0 % . Distant metastases were observed in 6 % . Lymph node metastases occurred more frequently as tumor size increased ( > 1 cm ) . The frequency of MEN-1 complications was 1 % . Physical examination revealed GI-NETs in 44 % patients . The frequency of symptomatic GI-NETs was 3.4 % . Interestingly , 77.1 % of patients with foregut GI-NETs had type A gastritis . Conclusion Our results show there are large differences in GEP-NETs between Japan and Western nations , primarily due to differences in the presence of MEN-1 in NF-PETs and the location , symptomatic status , and prevalence of malignancy in GI-NETs Background : In patients with well-differentiated ( WD ) neuroendocrine tumors ( NET ) , long-acting octreotide ( LAR ) , conventionally administered at a dose of 30 mg every 28 days , has well-documented anti-secretive but limited antiproliferative effects . Aim : The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations ( 21 days ) in WD-NET patients with progressive disease at st and ard-dose interval . Subjects and methods : Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled . Clinical , biological , and objective tumor response was evaluated after LAR 30 mg every 21 days . Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days . Results : The treatment with LAR 30 mg every 21 days result ed in complete and partial control of clinical symptoms in 40 % and 60 % of cases , respectively . Circulating neuroendocrine markers were significantly decreased in 30 % of cases . A stabilization of disease was obtained in 93 % and objective response in 7 % . The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the st and ard one ( 30 vs 9 months , p<0.0001 ) . The treatment was safe and well tolerated . Conclusions : The shortened schedule of LAR administration was able to re-institute control of clinical symptoms , to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a st and ard schedule treatment PURPOSE Despite the fact that most gastroenteropancreatic neuroendocrine tumors ( GEPNETs ) are slow-growing , median overall survival ( OS ) in patients with liver metastases is 2 to 4 years . In metastatic disease , cytoreductive therapeutic options are limited . A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate . Here we report on the toxicity and efficacy of this treatment , performed in over 500 patients . PATIENTS AND METHODS Patients were treated up to a cumulative dose of 750 to 800 mCi ( 27.8 - 29.6 GBq ) , usually in four treatment cycles , with treatment intervals of 6 to 10 weeks . Toxicity analysis was done in 504 patients , and efficacy analysis in 310 patients . RESULTS Any hematologic toxicity grade 3 or 4 occurred after 3.6 % of administrations . Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients , and temporary , nonfatal , liver toxicity in two patients . Complete and partial tumor remissions occurred in 2 % and 28 % of 310 GEPNET patients , respectively . Minor tumor response ( decrease in size > 25 % and < 50 % ) occurred in 16 % . Median time to progression was 40 months . Median OS from start of treatment was 46 months , median OS from diagnosis was 128 months . Compared with historical controls , there was a survival benefit of 40 to 72 months from diagnosis . CONCLUSION Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects . Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities . Compared with historical controls , there is a benefit in OS from time of diagnosis of several years BACKGROUND Cytotoxic chemotherapy is widely used for advanced , unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours ( NETs ) and the most commonly used regimen combines 5-fluorouracil with streptozocin . The NET01 trial was design ed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin . METHODS Patients with advanced , unresectable NETs of pancreatic , gastrointestinal foregut or unknown primary site were r and omised to receive three-weekly capecitabine ( Cap ) 625 mg/m(2 ) twice daily orally , streptozocin ( Strep ) 1.0 g/m(2 ) intravenously on day 1 , with or without cisplatin ( Cis ) 70 mg/m(2 ) intravenously on day 1 . The primary outcome measure was objective response . Secondary outcome measures included progression-free and overall survival , quality of life , toxicity and biochemical response . RESULTS 86 ( 44 CapStrep , 42 CapStrepCis ) patients were r and omised . Best objective response rate was 12 % ( 95 % confidence interval (CI)=2 - 22 % ) with CapStrep and 16 % ( 95 % CI=4 - 27.4 % ) with CapStrepCis . Disease-control rate was 80 % with CapStrep and 74 % with CapStrepCis . The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis . 44 % of CapStrep and 68 % of CapStrepCis patients experienced grade ≥3 adverse events . INTERPRETATION The efficacies of the novel CapStrep±Cis regimens were very similar . CapStrep was better tolerated than CapStrepCis . The trial was registered as EudraCT : 2004 - 005202 - 71 and IS RCT N : 35124268 INTRODUCTION The kidneys play an essential role in PRRT . The infusion of amino acids could reduce uptake in the kidney of radiolabelled peptides . The purpose of this study was to determine the extent of kidney damage post PRRT . MATERIAL AND METHODS 53 patients , with disseminated neuroendocrine tumours ( NET ) , received 3 - 5 cycles of up to a maximum 7.4 GBq/m2 calculated dose of 90Y-DOTATATE ( n = 25 ) and 90Y/177Lu-DOTATATE ( n = 28 ) . Creatinine levels were measured and glomerular filtration rates ( GFR ) were calculated . A mixed amino acid infusion was used for nephroprotection . RESULTS Patients treated with 90Y-DOTATATE had a mean creatinine level of 0.77 ± 0.19 mg/dL and a mean GFR ( mL/min/1.73 m2 ) of 103.6 ± 30.8 . Patients treated with 90Y/177Lu-DOTATATE had a mean creatinine level of 0.92 ± 0.33 mg/dL and a mean GFR of 84.7 ± 26.3 . In the follow up , among patients treated with 90Y-DOTATATE and 90Y/177Lu-DOTATATE , the mean GFR level at 12 months was 101.2 ± 31.3 v. 83.9 ± 25.2 , at 24 months 80.2 ± 32.7 v. 77.2 ± 31.1 , at 36 months 78.9 ± 42.1 v. 67.5 ± 9.7 , and 48 months 59.7 ± 15.2 v. 72.6 ± 11.2 . The mean yearly decrease in GFR was 4.5 mL in all treated patients ; for patients treated with 90Y-DOTATATE and 90Y/177Lu-DOTATATE it was 6.8 v. 3.0 , respectively . CONCLUSIONS 90Y/177Lu-DOTATATE treatment induced statistically significantly less change in kidney function compared to 90Y-DOTATATE Background : We evaluated the activity and safety profile of 177Lu-DOTATATE peptide receptor radionuclide therapy ( Lu-PRRT ) in patients with advanced G1-G2 pancreatic neuroendocrine tumors . Patients and Methods : Fifty-two consecutive patients were treated at two different therapeutic dosages of 18.5 or 27.8 GBq in five cycles , according to the patient 's kidney function and bone marrow reserve , which are known to be the critical organs in PRRT . Results : Twenty-six patients received a mean full dosage ( FD ) of 25.5 GBq ( range 20.7 - 27.8 ) and 26 a mean reduced dosage ( RD ) of 17.8 GBq ( range 11.1 - 19.9 ) . Both therapeutic dosages result ed in antitumor activity ( disease control rate in the entire case series 81 % ) , with 12 % complete response , 27 % partial response and 46 % stable disease in the FD group , whereas we observed 4 % complete response , 15 % partial response and 58 % stable disease in the RD group . Median progression-free survival was not reached in the FD group and was 20 months in the RD group . No major acute or delayed hematological toxicity occurred . Conclusion : 177Lu-DOTATATE peptide receptor radionuclide therapy showed antitumor activity in advanced pancreatic neuroendocrine tumors even at a reduced total activity of 18.5 GBq . However , progression-free survival was significantly longer ( p = 0.05 ) after a total activity of 27.8 GBq , which can thus be considered the recommended dosage in eligible patients PURPOSE To evaluate the quality of life ( QoL ) in patients with metastatic somatostatin receptor positive gastroenteropancreatic tumors treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ( (177)Lu-octreotate ) therapy . PATIENTS AND METHODS Fifty patients who had been treated with 600 to 800 mCi of (177)Lu-octreotate and had a follow-up of at least 3 months were studied . The patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Question naire C30 before therapy and at follow-up visit 6 weeks after the last cycle . Overall QoL and specific QoL domains of both the total group of patients and subgroups according to treatment outcome were analyzed . Twenty-four patients had regression , 19 had stable disease , six had progressive disease , and one had nonassessable disease status . Analysis of variance was used for statistical comparison . RESULTS A significant improvement in the global health status/QoL scale was observed after therapy with (177)Lu-octreotate ( P < .01 ) . The score increased significantly six weeks after therapy to a mean of 78.2 , up from 69.0 ( scale range , 0 to 100 ) . Furthermore , significant improvement was observed in the role , emotional , and social function scales . The symptom scores for fatigue , insomnia , and pain were significantly decreased . Patients with proven tumor regression most frequently had an improvement of QoL domains . Unexpectedly , patients with progressive disease also indicated an improvement in their global health/QoL score . CONCLUSION (177)Lu-octreotate therapy significantly improved the global health/QoL and several function and symptom scales in patients with metastasized gastroenteropancreatic tumors , but especially in those patients with proven tumor regression 194 Background : Currently , there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy . Methods : NETTER-1 is the first Phase III multicentric , r and omized , controlled trial evaluating 177Lu-DOTA0-Tyr3-Octreotate ( Lutathera ) in patients with inoperable , progressive , somatostatin receptor positive midgut NETs . 230 patients with Grade 1 - 2 metastatic midgut NETs were r and omized to receive Lutathera 7.4 GBq every 8 weeks ( x4 administrations ) versus Octreotide LAR 60 mg every 4-weeks . The primary endpoint was PFS per RECIST 1.1 criteria , with objective tumor assessment performed by an independent reading center every 12 weeks . Secondary objectives included objective response rate , overall survival , toxicity , and health-related quality of life . Results : Enrolment was completed in February 2015 , with a target of 230 patients r and omized ( 1:1 ) in 36 European and 15 sites in the United States . At the time of statistical analysis , AIDS Clinical Trial Group ( ACTG ) r and omized trial 021 compared the effect of bactrim versus aerosolized pentamidine ( AP ) as prophylaxis therapy for pneumocystis pneumonia ( PCP ) in AIDS patients . Although patients r and omized to the bactrim arm experienced a significant delay in time to PCP , the survival experience in the two arms was not significantly different ( p = .32 ) . In this paper , we present evidence that bactrim therapy improves survival but that the st and ard intent-to-treat comparison failed to detect this survival advantage because a large fraction of the subjects either crossed over to the other therapy or stopped therapy altogether . We obtain our evidence of a beneficial bactrim effect on survival by artificially regarding the subjects as dependently censored at the first time the subject either stops or switches therapy ; we then analyze the data with the inverse probability of censoring weighted Kaplan-Meier and Cox partial likelihood estimators of Robins ( 1993 , Proceedings of the Biopharmaceutical Section , American Statistical Association , pp . 24 - 33 ) that adjust for dependent censoring by utilizing data collected on time-dependent prognostic factors e21091 Background : In the phase III RADIANT-3 trial , everolimus , an oral mTOR inhibitor , demonstrated superiority in progression-free survival ( PFS ) with a median of 11.0 versus 4.6 months for placebo ( HR=0.35 ; p<0.0001 ) in patients with advanced pNET ( ESMO 2010 , abstract LBA9 ) . In order to determine the factors that significantly influence PFS , a prespecified multivariate analysis was performed . METHODS Patients with progressive advanced low- or intermediate- grade pNET were r and omized to receive everolimus 10 mg/d orally ( n=207 ) or placebo ( n=203 ) ; both arms received best supportive care . Primary endpoint was PFS . Multivariate analysis using a Cox-proportional hazards model was performed on the following factors : treatment ; age ; sex ; WHO performance status ; geographic region ; prior somatostatin use ; baseline CgA ; baseline NSE ; Ki67 ; years since diagnosis ; liver , bone , or extrahepatic involvement ; and number of organs involved . Significant factors ( p<0.05 ) were determined after a stepwise elimination of nonsignificant factors from the model . RESULTS Multivariate analysis indicated that significant prognostic factors of PFS were treatment ( everolimus vs placebo ) ( p<0.001 ) , WHO performance status ( p<0.001 ) , baseline NSE level ( p<0.001 ) , and liver involvement ( p=0.048 ) . CONCLUSIONS Multivariate analysis of the RADIANT-3 trial has allowed , for the first time , evaluation of prognostic factors associated with PFS in a large phase III , placebo-controlled trial in patients with advanced pNET . A better underst and ing of these risk factors can help clinicians in the treatment of their patients . [ Table : see text ] 4103 Background : In the phase III RADIANT-3 trial , everolimus ( EVE ) , an oral mTOR inhibitor , demonstrated superior progression-free survival ( PFS ) with a median of 11.0 vs 4.6 mo for placebo ( PBO ) ( HR=0.35 ; 95 % confidence interval , 0.27 - 0.45 ; P<0.0001 ) in pts with advanced pNET ( ESMO 2010 , Abstract # LBA9 ) . An exploratory analysis of prior chemotherapy use and PFS from the RADIANT-3 trial is presented . METHODS Pts with progressive advanced low- or intermediate- grade pNET were r and omized to EVE 10 mg/d orally ( n=207 ) or PBO ( n=203 ) ; both arms received best supportive care . The primary endpoint was PFS per central review ( RECIST v1.0 ) . Pts were stratified by use of prior vs no prior chemotherapy . RESULTS Overall , 206/410 ( 50 % ) pts received prior chemotherapy . Prior chemotherapy use was balanced in both arms : 104/207 ( 50 % ) EVE pts vs 102/203 ( 49 % ) PBO pts . No difference was observed in baseline characteristics ( age , sex , race , tumor type , histologic grade ) and baseline tumor biomarker levels for pts receiving prior chemotherapy vs those without . Time since initial diagnosis was > 2 years for 147 ( 71 % ) pts with prior chemotherapy vs 98 ( 48 % ) pts without prior chemotherapy . A higher proportion of pts with prior chemotherapy also had received prior somatostatin therapy ( 54 % prior chemotherapy vs 45 % no prior chemotherapy ) . A positive treatment effect with EVE was observed in pts both with and without prior chemotherapy . EVE significantly prolonged PFS vs placebo in pts with prior chemotherapy ( HR=0.34 ; P<0.0001 ) and those without prior chemotherapy ( HR=0.42 ; P<0.001 ) . Median PFS with EVE for pts with prior chemotherapy was 11.0 mo vs 11.4 mo for those without prior chemotherapy ( HR=1.120 ; 95 % CI , 0.768 - 1.634 ; P=0.56 ) . Median PFS with PBO for pts with prior chemotherapy was 3.2 mo vs 5.4 mo for those without prior chemotherapy ( HR=1.3 ; 95 % CI , 0.990 - 1.828 ; P=0.054 ) . CONCLUSIONS EVE demonstrated significantly longer median PFS than PBO in pts with advanced pNET , regardless of prior chemotherapy use . These results suggest that EVE should be considered a treatment option for pNET pts , including those without prior chemotherapy Objective Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors ( NETs ) . For the first time in the United States , we present preliminary results of the treatment with Lutetium 177 ( 177Lu ) DOTATATE in patients with progressive NETs . Methods Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonr and omized , phase 2 clinical trial . Repeated cycles of 200 mCi ( 7.4 GBq ; ±10 % ) were administered up to the cumulative dose of 800 mCi ( 29.6 GBq ; ±10 % ) . Results Among 32 evaluable patients , partial response and minimal response to treatment were seen in 28 % and 3 % , respectively , and stable disease was seen in 41 % of patients . A total of 28 % had progressive disease . A response to treatment was significantly associated with lower burden of disease in the liver . No significant acute or delayed hematologic or kidney toxicity was observed . An impressive improvement of performance status and quality of life were seen after 177Lu-DOTATATE therapy . Conclusions Treatment with multiple cycles of 177Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated . This treatment results in control of the disease in most patients , whereas systemic toxicities are limited and reversible . Quality of life is also improved ABSTRACT Aim : EVE significantly improved median progression-free survival vs PBO in patients ( pts ) with pNET by 6.4 months in RADIANT-3 ( 11.0 vs 4.6 months ; HR 0.35 , 95 % CI 0.27 - 0.45 ; p Methods : Pts with progressive advanced , low- or intermediate- grade pNET were r and omized to EVE 10mg/d ( n = 207 ) or PBO ( n = 203 ) ; both with best supportive care . Upon disease progression during double-blind phase , crossover from PBO to open-label EVE was allowed . At the time of unblinding ( cutoff , Jun 3 , 2010 ) , all ongoing pts transitioned into the extension phase to receive open-label EVE . After 256 events , OS analysis was performed using a stratified log-rank test in the intent-to-treat patient population ( N = 410 ; all r and omized pts ) . Results : Of 410 pts , 225 switched to open-label EVE ; including 85 % of pts initially r and omized to PBO ( 172 of 203 ) . Median open-label EVE exposure was 67.1 weeks ( range 1 - 189 ) in pts initially r and omized to EVE and 44.0 weeks ( range 0 - 261 ) in pts r and omized to PBO . Median OS ( 95 % CI ) was 44.0 ( 35.6 - 51.8 ) months for EVE arm and 37.7 ( 29.1 - 45.8 ) months for PBO arm ( HR 0.94 , 95 % CI 0.73 - 1.20 ; p = 0.30 ; boundary 0.0249 ) . Adverse events reported during the open-label phase ( n = 221 ) were consistent with those observed during blinded treatment ; the most common included stomatitis ( 47 % ) , diarrhea ( 44 % ) , and rash ( 40 % ) . Estimated OS rates Kaplan-Meier estimates [ 95 % CI ] at : EVE 10 mg/d ( n = 207 ) PBO ( n = 203 ) 12 mo 82.6 [ 76.6 - 87.2 ] 82.0 [ 75.9 - 86.7 ] 24 mo 67.7 [ 60.7 - 73.8 ] 64.0 [ 56.8 - 70.2 ] 36 mo 56.7 [ 49.4 - 63.3 ] 50.9 [ 43.6 - 57.7 ] 48 mo 46.9 [ 39.7 - 53.8 ] 41.3 [ 34.3 - 48.1 ] 60 mo 34.7 [ 27.7 - 41.7 ] 35.5 [ 28.7 - 42.4 ] Conclusions : EVE demonstrated a median OS of 44 months , the longest OS reported for progressive advanced pNET pts in a phase 3 study . A clinical ly important improvement of 6.3 months in median OS vs PBO was observed , although the difference did not reach statistical significance . Crossover of majority of pts ( 85 % ) may also have confounded OS . The safety of EVE was consistent with previous experience . Disclosure : J.C. Yao : Corporate-sponsored research ( Novartis ) ; Consultancy ( Novartis ) ; M. Pavel : Honoraria for advisory board meeting and presentations ( Novartis , IPSEN , Pfizer ) ; Research grant ( Novartis ) ; C. Lombard-Bohas : Membership on an advisory board or board of directors ( Novartis ) ; E. van Cutsem : Research grant paid to university by Novartis ; D. Lam : Employee ( Novartis ) ; Stock ownership ( Novartis ) ; T. Kunz : Employee ( Novartis ) ; Stock ownership ( Novartis ) ; U. Br and t : Employee ( Novartis ) ; Stock ownership ( Novartis ) ; E.G.E. De Vries : Support for the execution of the trial made available to the UMCG ; T. Hobday : Research funding ( Novartis ) ; R. Pommier : Consultant ( Novartis , Pfizer ) . All other authors have declared no conflicts of interest 249 Background : Sunitinib is an oral , multitargeted receptor tyrosine kinase inhibitor with antiangiogenic activity . In a phase III , double-blind , placebo-controlled , r and omized trial in patients with advanced , well-differentiated progressive pancreatic neuroendocrine tumors ( NET ) , sunitinib 37.5 mg continuous daily dosing significantly improved investigator-assessed progression-free survival ( PFS ) compared with placebo ( median , 11.4 months vs. 5.5 months ; hazard ratio [ HR ] 0.418 ; 95 % CI : 0.263 , 0.662 ; P=0.0001 ) . To evaluate the possibility that recognizable treatment- associated adverse events ( AEs ) might have impacted the efficacy results by unblinding the investigators , we conducted a retrospective blinded independent central review ( BICR ) of the tumor imaging scans . METHODS PFS was defined as the time from r and omization to the first objective progression of disease or death due to any cause , whichever occurred first . Baseline and on- study CT/MRI scans were evaluated independently according to a two-reader , two-time point lock , followed by a sequential locked read , batch mode paradigm , by independent , third party radiologists . Reading radiologists were blinded to investigator tumor assessment s and AEs ; discrepancies were adjudicated by a similarly blinded and independent third radiologist . RESULTS Overall , 171 patients were r and omized to treatment ( sunitinib , n=86 , placebo , n=85 ) . Scans were collected retrospectively for 170 ( 99.4 % ) patients . Complete scan sets/time points were available for 160 patients ( 93.6 % ) . Median PFS based on BICR of scans was 12.6 months for sunitinib and 5.8 months for placebo with an HR of 0.315 ( 95 % CI : 0.181 , 0.546 ; p=0.000015 ) , consistent with the investigator- assessed PFS results . CONCLUSIONS This BICR of tumor scans confirms the investigator-assessed , clinical ly meaningful PFS benefit of sunitinib in patients with pancreatic NET , and provides evidence against the presence of any systematic bias favoring sunitinib . [ Table : see text ] Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first‐line somatostatin analogue therapy have limited therapeutic options . This r and omized , controlled trial evaluated the efficacy and safety of lutetium‐177 (177Lu)–Dotatate in patients with advanced , progressive , somatostatin‐receptor – positive midgut neuroendocrine tumors . Methods We r and omly assigned 229 patients who had well‐differentiated , metastatic midgut neuroendocrine tumors to receive either 177Lu‐Dotatate ( 116 patients ) at a dose of 7.4 GBq every 8 weeks ( four intravenous infusions , plus best supportive care including octreotide long‐acting repeatable [ LAR ] administered intramuscularly at a dose of 30 mg ) ( 177Lu‐Dotatate group ) or octreotide LAR alone ( 113 patients ) administered intramuscularly at a dose of 60 mg every 4 weeks ( control group ) . The primary end point was progression‐free survival . Secondary end points included the objective response rate , overall survival , safety , and the side‐effect profile . The final analysis of overall survival will be conducted in the future as specified in the protocol ; a prespecified interim analysis of overall survival was conducted and is reported here . Results At the data ‐cutoff date for the primary analysis , the estimated rate of progression‐free survival at month 20 was 65.2 % ( 95 % confidence interval [ CI ] , 50.0 to 76.8 ) in the 177Lu‐Dotatate group and 10.8 % ( 95 % CI , 3.5 to 23.0 ) in the control group . The response rate was 18 % in the 177Lu‐Dotatate group versus 3 % in the control group ( P<0.001 ) . In the planned interim analysis of overall survival , 14 deaths occurred in the 177Lu‐Dotatate group and 26 in the control group ( P=0.004 ) . Grade 3 or 4 neutropenia , thrombocytopenia , and lymphopenia occurred in 1 % , 2 % , and 9 % , respectively , of patients in the 177Lu‐Dotatate group as compared with no patients in the control group , with no evidence of renal toxic effects during the observed time frame . Conclusions Treatment with 177Lu‐Dotatate result ed in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors . Preliminary evidence of an overall survival benefit was seen in an interim analysis ; confirmation will be required in the planned final analysis . Clinical ly significant myelosuppression occurred in less than 10 % of patients in the 177Lu‐Dotatate group . ( Funded by Advanced Accelerator Applications ; NETTER‐1 Clinical Trials.gov number , NCT01578239 ; EudraCT number 2011‐005049‐11 . Background / Methods : Thirty patients with advanced progressive grade 1 or 2 pancreatic neuroendocrine tumors ( pNETs ) , treated on a prospect i ve phase II single-center study , were followed up for up to 4 years after 4 cycles of 7.9 GBq 177Lu-octreotate combined with chemotherapy . Each 8-week cycle of treatment combined radiopeptide therapy with 14 days of capecitabine at 1,500 mg/m2 and 5 days of temozolomide at 200 mg/m2 . Results : The overall response rate was 80 % ( 95 % CI 66 - 93 ) , and there was complete remission in 13 % ( 95 % CI 4 - 30 ) and partial response in 70 % ( 95 % CI 52 - 83 ) of the cases . No patient manifested progressive disease on treatment . Median progression-free survival was 48 months . Median overall survival had not been reached at a median follow-up of 33 months . No patient was lost to follow-up , all but 1 received 4 cycles of outpatient therapy , and all were evaluated for response and toxicity . No one required hospital admission . The treatment was well tolerated , and no serious dose-limiting toxicities were seen . The commonest toxicity was transient nausea of grade 2 ( 33 % ) or 3 ( 7 % ) . Hematological toxicity was limited to grade 3 thrombocytopenia ( 10 % ) and anemia ( 10 % ) . There were no grade 4 adverse events , and no renal functional impairment was evident . Conclusion : Combined 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy is a well-tolerated , highly effective outpatient regimen for control of advanced progressive pNETs , achieving a durable objective response |
11,249 | 30,962,996 | Conclusions The incidence of high- grade and all- grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma .
High- grade adverse events were otherwise more common in the CTH arm .
Tumor response rate , PFS , and OS are all substantially improved with IMM over CTH . | Background Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types , although their high incidence of skin , gastrointestinal , and endocrine side effects with their use .
The risk of pneumonitis associated with checkpoint inhibition therapy is not well described . | AIM To evaluate the protocol -specified final analysis of overall survival ( OS ) in the KEYNOTE-002 study ( NCT01704287 ) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory , advanced melanoma . METHODS In this r and omised , phase II study , eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses , previous BRAF or MEK inhibitor or both , if BRAFV600 mutant-positive . Patients were r and omised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy . Crossover to pembrolizumab was allowed following progression on chemotherapy . The protocol -specified final OS was performed in the intent-to-treat population . Survival was positive if p < 0.01 in one pembrolizumab arm . RESULTS A total of 180 patients were r and omised to pembrolizumab 2 mg/kg , 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy . At a median follow-up of 28 months ( range 24.1 - 35.5 ) , 368 patients died and 98 ( 55 % ) crossed over to pembrolizumab . Pembrolizumab 2 mg/kg ( hazard ratio [ HR ] 0.86 , 95 % confidence interval [ CI ] 0.67 - 1.10 , p = 0.117 ) and 10 mg/kg ( 0.74 , 0.57 - 0.96 , p = 0.011 ) result ed in a non-statistically significant improvement in OS versus chemotherapy ; median OS was 13.4 ( 95 % CI 11.0 - 16.4 ) and 14.7 ( 95 % CI 11.3 - 19.5 ) , respectively , versus 11.0 months ( 95 % CI 8.9 - 13.8 ) , with limited improvement after censoring for crossover . Two-year survival rates were 36 % and 38 % , versus 30 % . Progression-free survival , objective response rate and duration of response improved with pembrolizumab versus chemotherapy , regardless of dose . Grade III-V treatment-related adverse events occurred in 24 ( 13.5 % ) , 30 ( 16.8 % ) and 45 ( 26.3 % ) patients , respectively . CONCLUSION Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors . We assessed the efficacy and safety of nivolumab compared with investigator 's choice of chemotherapy ( ICC ) as a second-line or later-line treatment in patients with advanced melanoma . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients at 90 sites in 14 countries . Eligible patients were 18 years or older , had unresectable or metastatic melanoma , and progressed after ipilimumab , or ipilimumab and a BRAF inhibitor if they were BRAF(V 600 ) mutation-positive . Participating investigators r and omly assigned ( with an interactive voice response system ) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC ( dacarbazine 1000 mg/m(2 ) every 3 weeks or paclitaxel 175 mg/m(2 ) combined with carboplatin area under the curve 6 every 3 weeks ) until progression or unacceptable toxic effects . We stratified r and omisation by BRAF mutation status , tumour expression of PD-L1 , and previous best overall response to ipilimumab . We used permuted blocks ( block size of six ) within each stratum . Primary endpoints were the proportion of patients who had an objective response and overall survival . Treatment was given open-label , but those doing tumour assessment s were masked to treatment assignment . We assessed objective responses per- protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks , and safety in all patients who had had at least one dose of treatment . The trial is closed and this is the first interim analysis , reporting the objective response primary endpoint . This study is registered with Clinical Trials.gov , number NCT01721746 . FINDINGS Between Dec 21 , 2012 , and Jan 10 , 2014 , we screened 631 patients , r and omly allocating 272 patients to nivolumab and 133 to ICC . Confirmed objective responses were reported in 38 ( 31·7 % , 95 % CI 23·5 - 40·8 ) of the first 120 patients in the nivolumab group versus five ( 10·6 % , 3·5 - 23·1 ) of 47 patients in the ICC group . Grade 3 - 4 adverse events related to nivolumab included increased lipase ( three [ 1 % ] of 268 patients ) , increased alanine aminotransferase , anaemia , and fatigue ( two [ 1 % ] each ) ; for ICC , these included neutropenia ( 14 [ 14 % ] of 102 ) , thrombocytopenia ( six [ 6 % ] ) , and anaemia ( five [ 5 % ] ) . We noted grade 3 - 4 drug-related serious adverse events in 12 ( 5 % ) nivolumab-treated patients and nine ( 9 % ) patients in the ICC group . No treatment-related deaths occurred . INTERPRETATION Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor . Nivolumab represents a new treatment option with clinical ly meaningful durable objective responses in a population of high unmet need . FUNDING Bristol-Myers Squibb BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) 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 Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy . Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P<0.001 ) . The estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . ) BACKGROUND Despite recent advances in the treatment of advanced non-small-cell lung cancer , there remains a need for effective treatments for progressive disease . We assessed the efficacy of pembrolizumab for patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . METHODS We did this r and omised , open-label , phase 2/3 study at 202 academic medical centres in 24 countries . Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1 % of tumour cells were r and omly assigned ( 1:1:1 ) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg , pembrolizumab 10 mg/kg , or docetaxel 75 mg/m(2 ) every 3 weeks . The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50 % of tumour cells . We used a threshold for significance of p<0.00825 ( one-sided ) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival . This trial is registered at Clinical Trials.gov , number NCT01905657 . FINDINGS Between Aug 28 , 2013 , and Feb 27 , 2015 , we enrolled 1034 patients : 345 allocated to pembrolizumab 2 mg/kg , 346 allocated to pembrolizumab 10 mg/kg , and 343 allocated to docetaxel . By Sept 30 , 2015 , 521 patients had died . In the total population , median overall survival was 10.4 months with pembrolizumab 2 mg/kg , 12.7 months with pembrolizumab 10 mg/kg , and 8.5 months with docetaxel . Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel ( hazard ratio [ HR ] 0.71 , 95 % CI 0.58 - 0.88 ; p=0.0008 ) and for pembrolizumab 10 mg/kg versus docetaxel ( 0.61 , 0.49 - 0.75 ; p<0.0001 ) . Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg , 4.0 months with pembrolizumab 10 mg/kg , and 4.0 months with docetaxel , with no significant difference for pembrolizumab 2 mg/kg versus docetaxel ( 0.88 , 0.74 - 1.05 ; p=0.07 ) or for pembrolizumab 10 mg/kg versus docetaxel ( HR 0.79 , 95 % CI 0.66 - 0.94 ; p=0.004 ) . Among patients with at least 50 % of tumour cells expressing PD-L1 , overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 14.9 months vs 8.2 months ; HR 0.54 , 95 % CI 0.38 - 0.77 ; p=0.0002 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 17.3 months vs 8.2 months ; 0.50 , 0.36 - 0.70 ; p<0.0001 ) . Likewise , for this patient population , progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel ( median 5.0 months vs 4.1 months ; HR 0.59 , 95 % CI 0.44 - 0.78 ; p=0.0001 ) and with pembrolizumab 10 mg/kg than with docetaxel ( 5.2 months vs 4.1 months ; 0.59 , 0.45 - 0.78 ; p<0.0001 ) . Grade 3 - 5 treatment-related adverse events were less common with pembrolizumab than with docetaxel ( 43 [ 13 % ] of 339 patients given 2 mg/kg , 55 [ 16 % ] of 343 given 10 mg/kg , and 109 [ 35 % ] of 309 given docetaxel ) . INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated , PD-L1-positive , advanced non-small-cell lung cancer . These data establish pembrolizumab as a new treatment option for this population and vali date the use of PD-L1 selection . FUNDING Merck & BACKGROUND Nivolumab , a programmed death 1 ( PD-1 ) checkpoint inhibitor , was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma . This r and omized , open-label , phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment . METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were r and omly assigned ( in a 1:1 ratio ) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily . The primary end point was overall survival . The secondary end points included the objective response rate and safety . RESULTS The median overall survival was 25.0 months ( 95 % confidence interval [ CI ] , 21.8 to not estimable ) with nivolumab and 19.6 months ( 95 % CI , 17.6 to 23.1 ) with everolimus . The hazard ratio for death with nivolumab versus everolimus was 0.73 ( 98.5 % CI , 0.57 to 0.93 ; P=0.002 ) , which met the prespecified criterion for superiority ( P≤0.0148 ) . The objective response rate was greater with nivolumab than with everolimus ( 25 % vs. 5 % ; odds ratio , 5.98 [ 95 % CI , 3.68 to 9.72 ] ; P<0.001 ) . The median progression-free survival was 4.6 months ( 95 % CI , 3.7 to 5.4 ) with nivolumab and 4.4 months ( 95 % CI , 3.7 to 5.5 ) with everolimus ( hazard ratio , 0.88 ; 95 % CI , 0.75 to 1.03 ; P=0.11 ) . Grade 3 or 4 treatment-related adverse events occurred in 19 % of the patients receiving nivolumab and in 37 % of the patients receiving everolimus ; the most common event with nivolumab was fatigue ( in 2 % of the patients ) , and the most common event with everolimus was anemia ( in 8 % ) . CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma , overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus . ( Funded by Bristol-Myers Squibb ; CheckMate 025 Clinical Trials.gov number , NCT01668784 . ) Background Patients with advanced urothelial carcinoma that progresses after platinum‐based chemotherapy have a poor prognosis and limited treatment options . Methods In this open‐label , international , phase 3 trial , we r and omly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum‐based chemotherapy to receive pembrolizumab ( a highly selective , humanized monoclonal IgG4κ isotype antibody against programmed death 1 [ PD‐1 ] ) at a dose of 200 mg every 3 weeks or the investigator 's choice of chemotherapy with paclitaxel , docetaxel , or vinflunine . The co primary end points were overall survival and progression‐free survival , which were assessed among all patients and among patients who had a tumor PD‐1 lig and ( PD‐L1 ) combined positive score ( the percentage of PD‐L1–expressing tumor and infiltrating immune cells relative to the total number of tumor cells ) of 10 % or more . Results The median overall survival in the total population was 10.3 months ( 95 % confidence interval [ CI ] , 8.0 to 11.8 ) in the pembrolizumab group , as compared with 7.4 months ( 95 % CI , 6.1 to 8.3 ) in the chemotherapy group ( hazard ratio for death , 0.73 ; 95 % CI , 0.59 to 0.91 ; P=0.002 ) . The median overall survival among patients who had a tumor PD‐L1 combined positive score of 10 % or more was 8.0 months ( 95 % CI , 5.0 to 12.3 ) in the pembrolizumab group , as compared with 5.2 months ( 95 % CI , 4.0 to 7.4 ) in the chemotherapy group ( hazard ratio , 0.57 ; 95 % CI , 0.37 to 0.88 ; P=0.005 ) . There was no significant between‐group difference in the duration of progression‐free survival in the total population ( hazard ratio for death or disease progression , 0.98 ; 95 % CI , 0.81 to 1.19 ; P=0.42 ) or among patients who had a tumor PD‐L1 combined positive score of 10 % or more ( hazard ratio , 0.89 ; 95 % CI , 0.61 to 1.28 ; P=0.24 ) . Fewer treatment‐related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group ( 60.9 % vs. 90.2 % ) ; there were also fewer events of grade 3 , 4 , or 5 severity reported in the pembrolizumab group than in the chemotherapy group ( 15.0 % vs. 49.4 % ) . Conclusions Pembrolizumab was associated with significantly longer overall survival ( by approximately 3 months ) and with a lower rate of treatment‐related adverse events than chemotherapy as second‐line therapy for platinum‐refractory advanced urothelial carcinoma . ( Funded by Merck ; KEYNOTE‐045 Clinical Trials.gov number , NCT02256436 . PURPOSE Programmed death 1 is an immune checkpoint that suppresses antitumor immunity . Nivolumab , a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody , was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts . We report overall survival ( OS ) , response durability , and long-term safety in patients with non-small-cell lung cancer ( NSCLC ) receiving nivolumab in this trial . PATIENTS AND METHODS Patients ( N = 129 ) with heavily pretreated advanced NSCLC received nivolumab 1 , 3 , or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks . Tumor burden was assessed by RECIST ( version 1.0 ) after each cycle . RESULTS Median OS across doses was 9.9 months ; 1- , 2- , and 3-year OS rates were 42 % , 24 % , and 18 % , respectively , across doses and 56 % , 42 % , and 27 % , respectively , at the 3-mg/kg dose ( n = 37 ) chosen for further clinical development . Among 22 patients ( 17 % ) with objective responses , estimated median response duration was 17.0 months . An additional six patients ( 5 % ) had unconventional immune-pattern responses . Response rates were similar in squamous and nonsquamous NSCLC . Eighteen responding patients discontinued nivolumab for reasons other than progressive disease ; nine ( 50 % ) of those had responses lasting > 9 months after their last dose . Grade 3 to 4 treatment-related adverse events occurred in 14 % of patients . Three treatment-related deaths ( 2 % of patients ) occurred , each associated with pneumonitis . CONCLUSION Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC . R and omized clinical trials with nivolumab in advanced NSCLC are ongoing |
11,250 | 26,120,804 | Although due to variability in studies ( inclusion criteria , outcome variables and interventions ) and the evidence is not of highest quality , we still believe that NSAIDs are an effective treatment for renal colic when compared to placebo or antispasmodics .
The addition of antispasmodics to NSAIDS does not result in better pain control .
Major adverse effects are not reported in the literature for the use of NSAIDs for treatment of renal colic | BACKGROUND Renal colic is acute pain caused by urinary stones .
The prevalence of urinary stones is between 10 % and 15 % in the United States , making renal colic one of the common reasons for urgent urological care .
The pain is usually severe and the first step in the management is adequate analgesia .
Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics .
OBJECTIVES The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication ( or class of medications ) are more appropriate for this purpose .
Clinical ly relevant outcomes such as efficacy of pain relief , time to pain relief , recurrence of pain , need for rescue medication and side effects were explored . | The aim of this study is to compare the effectiveness of the 5-HT3 antagonist , ondansetron and a non-steroidal anti-inflammatory agent , diclofenac sodium , as a pain reliever in the treatment of acute ureteral colic . Sixty four patients with severe or moderate pain who were clinical ly diagnosed as having ureteral colic associated with microscopic or gross hematuria were included in the study . Thirty three patients were administered ondansetron and 31 patients were administered diclofenac sodium . Exclusion critera were known kidney or liver disease causing dysfunction , known hypersensitivity to ondansetron or diclofenac sodium , pregnancy , lactation , duodenal ulcer or bleeding . After pain assessment with a verbal scale and a visual analog scale ( VAS ) , we r and omized patients and administered 8 mg ondansetron intravenously to 33 patients and 75 mg diclofenac sodium intramuscularly to 31 patients and pain scores were recorded every 15 minutes . If significant pain relief was not achieved within 60 minutes , IV meperidine was given as rescue pain medication . Ondansetron was effective as a primary pain reliever in 14 ( 42.4 % ) patients , whereas 19 patients required additional medication . Diclofenac sodium was effective as a primary pain reliever in 24 ( 77.4 % ) patients , whereas 7 patients required additional medication . Ondansetron was not superior to diclofenac sodium in relieving pain in patients with acute ureteral colic Eighty-six patients with ureteral colic were included in a r and omised , prospect i ve , double-blind study of the analgesic efficacy and tolerance of ketoprofen versus diclofenac , both administered intramuscularly . There were no significant differences regarding pain-relief or side-effects The aim of this study was to assess the efficacy of desmopressin nasal spray compared with diclofenac given intramuscularly in patients with acute renal colic caused by urolithiasis . The study included 72 patients r and omized into three different groups : group A received desmopressin ( 40 mg , nasal spray ) , group B diclofenac ( 75 mg ) intramuscularly and group C , both desmopressin and diclofenac . Pain was assessed using a visual analogue scale at baseline , 10 , 30 min and 1 h after administering the treatments . Rescue analgesia was given at 30 min if needed . On admission , the pain level was the same in all three groups ( group A 85 ; and group B and C 90 each ) . At 10 min the pain decreased minimally in all the groups but more in group B and C ( group A 80 and group B and C 70 each ) . At 30 min pain scores were 75 , 37.5 and 40 for group A , B and C , respectively , indicating that there was no significant pain relief in desmopressin group . Rescue analgesic had to be given to all patients in group A and two patients in group B and three patients in group C. Pain relief in the desmopressin only group was significantly less at 1 h even after rescue analgesia ( pain scores of 27.5 , 15 and 20 for group A , B and C respectively ) . Intranasal desmopressin is not an effective analgesic in renal colic : exerts mild analgesic effect over a period of 30 min . It does not potentiate the effect of diclofenac Objective The aim of this study was to assess the efficacy and safety of a single intravenous ( i.v . ) bolus of dexketoprofen trometamol compared with an i.v . infusion of dipyrone in patients with moderate to severe pain due to renal colic . Methods A total of 308 patients with renal colic and visual analog scale ( VAS ) score ≥40 mm participated in a multicenter , r and omized , double blind , double-dummy , parallel , and active-controlled study and were r and omized to dexketoprofen 25 mg ( n = 101 ) , dexketoprofen 50 mg ( n = 104 ) , and dipyrone 2 g ( n = 103 ) . Results Mean [ ± st and ard deviation ( SD ) ] total pain relief ( TOTPAR ) scores were similar in the dexketoprofen 50 mg ( 15.3 ± 8.6 ) and dipyrone ( 15.5 ± 8.6 ) and slighly higher than in dexketoprofen 25 mg ( 13.5 ± 8.6 ) , although significant differences were not achieved . In the same way , patients in the dexketoprofen 50 mg and dipyrone groups showed higher scores in the sum of pain intensity differences ( SPID ) and the sum of analogue pain intensity differences ( SAPID ) than patients in the dexketoprofen 25 mg group , reaching statistical significance in comparison with dexketoprofen 25 mg and dipyrone for SPID and SAPID ( p < 0.05 ) . The time – effect course for pain intensity differences and pain relief showed significantly higher values for both doses of dexketoprofen during the first 30 min after drug administration ( p < 0.05 ) . Dexketoprofen 50 mg and dipyrone groups had 66 % and 70 % , respectively , of patients with at least 50 % of maximum obtainable TOTPAR in comparison with 56 % in the dexketoprofen 25 mg group . The study medications were well tolerated . Conclusions Dexketoprofen 50 mg administered as a single i.v . bolus was effective for the relief of moderate to severe pain in patients with renal colic , with a good safety profile and efficacy similar to i.v . dipyrone 2 g. Dexketoprofen produced analgesia that was faster in onset Intravenous indoprofen ( 400 mg ) , a cyclooxygenase inhibitor , was compared with intramuscular oxicodone hydrochloride (= oxicone 10 mg ) , a narcotic analgesic agent , in regard to efficacy and side effects in the treatment of renal colic . Oxicone was combined with papaverine ( 20 mg ) . Patients were r and omized to either treatment , and the drugs were given in double-dummy fashion , i.e. one injection of active drug plus one placebo injection . Pain intensity before and after treatment was registered by the patient ( visual analog scale ) and by a nurse , who also registered side effects . Oxicone was given to 46 patients and indoprofen to 48 . The groups did not differ in body weight , age , sex distribution , or pretreatment intensity of pain . More patients required additional treatment in the oxicone than in the indoprofen group ( 19 v. 10 ) . At 2 - 5 min after injection , pain reduction was greater with indoprofen , and more patients in this group had pain relief after 3 - 5 hours . Side effects were less frequent with indoprofen than with oxicone ( 1 v. 20 patients ) , in particular from the central nervous system . This difference probably was related to indoprofen 's slow and poor penetration of the blood-brain barrier . The study affirmed that non-narcotic cyclooxygenase inhibitors can replace narcotic analgesics for acute pain alleviation in renal colic . Indoprofen seems to be a useful alternative , with low risk of central nervous side effects Summary To investigate the combined analgesic and spasmolytic effect of dipyrone , 104 patients suffering from “ severe ” or “ excruciating ” colic pain due to a confirmed calculus in the upper urinary tract were r and omized to receive i.v . either 2.5 g dipyrone ( 36 patients ) , 100 mg tramadol ( 35 patients ) , or 20 mg butylscopolamine ( 33 patients ) in a multicentre , observer-blind , parallel-group study conducted in 8 German centres . The three treatment groups were homogeneous when analyzed by age , sex , height , and baseline pain intensity . Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint , pain intensity differences ( PID ) at 20 , 30 , and 50 min after drug administration , and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint , pain intensity differences on a categorical scale . Dipyrone had the highest SPID0–2 h of the three drugs ( P<0.05 ) . Only 5 patients receiving dipyrone needed “ rescue ” medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine . Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol . “ Distinct ” pain relief as assessed on a visual analogue scale ( VAS ) is a reliable method of determining the onset of analgesic action in the colic pain model To determine the effects of indomethacin suppositories in the relief of acute colic and prevention of recurrent colic , we instituted a prospect i ve double-blind , placebo-controlled protocol . Patients were r and omized to receive either 50 mg . indomethacin or placebo suppositories every 8 hours and all patients received prescriptions for supplemental narcotics to be used on an as needed basis . Relief of colic was assessed by counting the total number of supplemental narcotics used by each patient per 24 hours during the study period , which was defined as until passage of the calculus or 5 days . There were 41 patients entered into the study protocol and complete followup was available for 26 . Mean calculus size was 3.4 mm . in the indomethacin group versus 3.1 mm . in the placebo group . All 13 patients in the control group had recurrent episodes of colic and 8 of these 13 had more than 1 recurrent episode . Five patients in the placebo group required admission to the hospital for control of pain . In contrast , only 4 of the 13 patients in the treatment group had colic and only 1 had more than 1 episode of colic . No patient in the active drug group required admission to the hospital for control of pain . Over-all the ratio of supplemental narcotic used by the placebo group versus the indomethacin group was 7.6:1 ( p less than 0.005 ) . The mean interval time to passage of the calculus was slightly lower in the indomethacin group ( 89 versus 82 hours ) but this difference was not statistically significant ( p greater than 0.10 ) . Our data strongly support the use of indomethacin suppositories in the prevention of recurrent colic secondary to ureteral calculi The effect of glucagon administered as a bolus ( 1 mg ) followed by a continuous infusion ( 2 mg/h ) for 8 h and a placebo was compared in 37 adults with urographically demonstrated ureteral calculi less than 6 mm . The bolus injection was given 20 min after start of intravenous urography , and the infusion was initiated immediately afterwards . No effect on pain relief or passage of calculi was found . Nausea and /or vomiting were recorded significantly more frequently in patients who had glucagon than in patients who had the placebo . It is concluded that glucagon is of no value in acute ureteral colic A comparative , r and omized , double-blind study of diclofenac sodium 75 mg i m versus Baralgin ( a combination drug composed of dipyrone and two spasmolytics ) 5 mL iv was performed on 57 patients with renal colic . Both groups were comparable as to age , sex , pain evolution time before treatment , and no treatment for renal colic in the six hours preceding trial drug administration . No significant differences were found between the two groups with respect to the evolution of pain after the first dose or in the frequency of administration of a second dose . Tolerability was good in both groups , but sweating and pain throughout the vein were observed in one patient in the Baralgin group . We concluded that diclofenac sodium constitutes an excellent alternative to pyrazolone analgesics , with the advantages of being monotherapy and having good tolerability , when used as intramuscular injection in ambulatory patients In an open investigation , ciramadol , a partial agonist opioid , was found to be a potent analgesic when given intravenously in patients experiencing renal colic . Single intravenous doses of 20 , 30 and 40 mg of ciramadol were given to 11 , 11 and 12 patients with renal colic , respectively , and good pain relief was obtained in 10 , 11 and 10 patients , respectively . Vomiting and nausea occurred in 9 patients , 4 in the 20 mg group , 2 in the 30 mg group and 3 in the 40 mg group . This adverse effect was related to st and ing and walking following the ciramadol injection PURPOSE To study the safety and efficacy of intranasal desmopressin and intramuscular tramadol versus pethidine for treatment of renal colic . MATERIAL S AND METHODS A total of 90 adult patients who presented with renal colic to the emergency wards were recruited in this study . The patients were r and omly assigned to receive 100 mg intramuscular tramadol , 40µ g intranasal desmopressin , or 40µ g intranasal desmopressin plus 100 mg intramuscular tramadol . The severity of the pain was assessed using Visual Analogue Scale . RESULTS The studied patients consisted of 49 men and 41 women with the mean age of 35.20 ± 13.26 years ( range , 16 to 82 years ) . There was no statistically significant difference regarding the mean age ( F [ 2 , 89 ] = 2.98 , P = .056 ) and gender differences ( X2 = 3.3 , df = 2 , P = .19 ) in three groups . There was also no statistically significant difference considering pain relief in 3 studied groups ( P = .2 ) . CONCLUSION We concluded that narcotics such as pethidine can not be replaced by tramadol in patients with renal colic , but tramadol , desmopressin , or both in combination can reduce pethidine requirement OBJECTIVES To evaluate the therapeutic effect of papaverine hydrochloride in the treatment of patients with renal colic pain unresponsive to conventional treatment . METHODS From March 2007 to January 2008 , a total of 561 patients with severe renal colic pain due to a ureteral stone were treated with conventional agents ( hyoscine-N-butylbromide and diclofenac sodium ) in the emergency and urology departments . Of these 561 patients , 110 , with no response to the treatment and persistent severe pain , were r and omized into 3 groups for additional treatment . The patients in group 1 ( n = 37 ) received intravenous hyoscine-N-butylbromide , those in group 2 ( n = 37 ) received papaverine hydrochloride , and those in group 3 ( n = 36 ) received pethidine . Before and after treatment , all patients completed a visual analog scale ( VAS ) question naire , with a scale of 0 ( no pain ) to 10 ( maximal complaint ) , to measure their subjective pain . The mean VAS score of each group was compared with that of the other groups . RESULTS The pretreatment mean VAS scores of all 3 groups were not significantly different statistically from each other ( 4.02 + /- 1.20 , 4.36 + /- 1.97 , and 4.27 + /- 1.50 ; P > .05 ) . However , after treatment , the mean VAS scores of the patients treated with papaverine ( 0.93 + /- 0.29 ) and pethidine ( 0.81 + /- 0.38 ) were significantly different from those of the hycosine group ( 3.67 + /- 2.21 ; P < .001 ) . However , the mean VAS scores of groups 2 and 3 were comparable ( P = .67 ) . Unlike opioids , no papaverine-related severe side effects were observed . CONCLUSIONS Our results indicate that papaverine hydrochloride can used in an effective manner in the management of renal colic pain in patients unresponsive to commonly used conventional agents The analgesic effect of ceruletide in biliary and renal colic was evaluated by a r and omized , double-blind study in 82 patients . Ceruletide was compared with pentazocine , a well-established analgetic agent . Rapid and effective analgesia was obtained by intramuscular injection of ceruletide 0.5 μg/kg in 56 patients with biliary colic . The analgesic effect of ceruletide compared well with pentazocine 0.5 mg/kg i m , and was associated with remarkably fewer side effects . In 26 patients with renal colic , ceruletide was significantly inferior to pentazocine . These data support the recommendation of ceruletide as a first-choice analgetic agent for biliary colic A double-blind controlled study was design ed to compare the effective- ness of a single intramuscular dose of 60 mg ketorolac with that of 75 mg diclofenac in the treatment of renal colic and to monitor side effects . Fifty-seven patients completed the study , 27 in the ketorolac group and 30 in the diclofenac group . Effectiveness of treatment was monitored by pain relief reported on a 4-point verbal scale at different time points . At 60 minutes 77.8 % and 86.6 % ( P = 0.4 ) of patients , and at 120 minutes 81.5 % and 96.6 % ( P = .1 5 ) of patients , reported significant pain relief following ketorolac and diclofenac doses , respectively . Both groups had an equal 92 % significant pain relief at discharge from the emergency department . Both drugs were well tolerated by the patients . Ketorolac therefore , seems as effective as diclofenac in the treatment of renal colic In a double-blind trial 30 patients with renal colic were allocated at r and om to receive 200 mg of ketoprofen , 1 gm of lysine acetylsalicylate , or placebo by intravenous bolus injection . The patients were asked to rate their pain at intervals within three hours of injection and to indicate on a visual analogue scale the overall pain relief obtained . Both ketoprofen and lysine acetylsalicylate proved significantly more effective than placebo , with no apparent difference between them . Complete relief of pain was obtained in seven of ten patients in each of the active treatment groups compared with only one of ten patients given placebo . No untoward events were observed in any patient Objective To determine the effectiveness of isosorbide dinitrate in combination with tenoxicam compared with tenoxicam alone for the relief of acute renal colic OBJECTIVE We have conducted a clinical trial to compare the pain-relieving effect and safety of diclofenac administered intramuscularly to indomethacin given intravenously . METHODS The study was design ed as a r and omized single-blind trial . It was carried out at Oslo Emergency Hospital ( outpatient setting or stay < 24 h ) . 41 patients with a mean age of 41.6 years received 75 mg diclofenac and 42 patients with a mean age of 45.2 years were given 50 mg indomethacin . The two groups were similar in regard to baseline characteristics except gender distribution . RESULTS Statistically significant reduction in pain intensity was achieved after 5 min in the diclofenac group ( p < 0.01 ) , and after 10 min in the indomethacin group ( p < 0.01 ) . The probability of having pain after 1 h was 52 % in the indomethacin group and 37 % in the diclofenac group ( p = 0.11 ) . Rescue medication with pethidine after 2 h was given in 9 and 5 patients , respectively . Four patients in the diclofenac group reported one occurrence of adverse effect each , while 9 patients on indomethacin experienced 14 occurrences , mainly dizziness and nausea . CONCLUSION These findings together with a simpler mode of administration indicate that diclofenac may be preferred in the analgesic treatment of renal colic BACKGROUND In a l and mark hypothesis-generating study , Todd et al found that a difference of approximately 13 mm ( 95 % confidence interval [ CI ] 10 to 17 mm ) on a visual analog scale ( VAS ) represented the minimum change in acute pain that was clinical ly significant in a cohort of trauma patients . STUDY OBJECTIVE We test the hypothesis that the minimum clinical ly significant change in pain as measured by the VAS in an independent , more heterogeneous validation cohort is approximately 13 mm . METHODS This was a prospect i ve , observational cohort study of adults presenting to 2 urban emergency departments with pain . At 30-minute intervals during a 2-hour period , patients marked a VAS and were asked if their pain was " much less , " " a little less , " " about the same , " " a little more , " or " much more . " All data were obtained without reference to prior VAS scores . The minimum clinical ly significant change in pain was defined a priori as the difference in millimeters between the current and immediately preceding VAS scores when " a little more " or " a little less pain " was reported . RESULTS Ninety-six patients enrolled in the study , providing 332 paired pain measurements . There were 141 paired measurements design ated by patients as " a little less " or " a little more " pain . The mean clinical ly significant difference between consecutive ratings of pain in the combined " little less " or " little more " groups was 13 mm ( 95 % CI 10 to 16 mm ) . The difference between this finding and that of Todd et al was 0 mm ( 95 % CI -4 to 4 mm ) . CONCLUSION These data are virtually identical to previous findings indicating that a difference of 13 mm on a VAS represents , on average , the minimum change in acute pain that is clinical ly significant OBJECTIVES To determine the effect of the combination of intranasal desmopressin spray and diclofenac sodium suppository on acute renal colic and compare it with diclofenac sodium suppository alone . METHODS A total of 150 patients aged 15 - 65 years referred to our hospital with acute renal colic were included in a double-blind controlled clinical trial study . Patients in group 1 received desmopressin , 40 microg intranasally plus diclofenac sodium suppository 100 mg , and patients in group 2 received diclofenac sodium suppository 100 mg plus a placebo spray consisting of normal saline 0.9 % . RESULTS Significant differences were found in the pain scores at 15 and 30 minutes between the 2 groups ( P < .05 ) . Also , significant differences were found in the mean pain scores in the first 15 and first 30 minutes after treatment between the 2 groups ( P < .05 ) . Of the patients in group 1 , 37.3 % had no pain relief and required pethidine . However , this rate in group 2 was 69.3 % . In 17 cases , we prescribed pethidine within 20 minutes after treatment , and these patients were excluded from our study . CONCLUSIONS According to our results , intranasal desmopressin plus diclofenac sodium suppository caused prompt pain relief with significant decreases in pain scores after 15 and 30 minutes . We suggest that intranasal desmopressin spray is a useful supplemental therapy for renal colic in combination with nonsteroidal anti-inflammatory drugs , especially to reduce the use of opioids OBJECTIVE To evaluate the analgesic efficacy and safety of intramuscular drotaverine hydrochloride vs diclofenac sodium in treatment of acute renal colic . METHODS We conducted a r and omized , single-blind study comparing single intramuscular doses of drotaverine hydrochloride ( 80 mg ) vs diclofenac sodium ( 75 mg ) on 100 patients ( 50 in each arm ) presenting to the emergency department ( ED ) with renal colic . Subjects with inadequate pain relief at 30 minutes received rescue intramuscular tramadol ( 100 mg ) . Pain intensity was recorded using a visual analog scale ( VAS ) , which is the primary outcome measure of this study , before drug administration and 30 and 60 minutes afterwards . The drug effectiveness was defined as ≥50 % decrease in pain intensity 60 minutes after intramuscular administration , without exacerbation during the following 2 hours . The need for rescue medication and the presence of adverse effects were considered as secondary outcome of the study . RESULT VAS decreased significantly ( P < 0.001 ) with both drotaverine ( 52.4 % ) and diclofenac ( 49 % ) at 30 minutes . Reduction of VAS at 60 minutes was 61.3 % with drotaverine in comparison to 60.4 % with diclofenac . Forty-five patients ( 90 % ) in the drotaverine group and 44 ( 88 % ) in the diclofenac group found the therapy effective . The need for rescue medication was in five patients of the drotaverine group and six patients in the diclofenac group . There was no significant difference in safety profile in the study groups . CONCLUSION The efficacy and safety of drotaverine as analgesic in renal colic is noninferior to diclofenac and may be used as an alternative or add-on therapy to currently available options Background Despite the fact that numerous medications have been introduced to treat renal colic , none has been proven to relieve the pain rapidly and thoroughly . In this study , we aim ed at comparing the effects of intravenous lidocaine versus intravenous morphine in patients suffering from renal colic . Methods In a prospect i ve r and omized double-blind clinical trial performed in the emergency department of Imam Reza educational hospital of Tabriz , Iran , we studied 240 patients , 18–65 years old , who were referred due to renal colic . Patients were divided into two groups . In group I ( 120 people ) single-dose intravenous lidocaine ( 1.5 mg/kg ) was administered and in group II ( 120 people ) single-dose intravenous morphine ( 0.1 mg/kg ) was administered slowly . Visual Analogue Pain Scale ( VAS ) was recorded while admission , 5 , 10 , 15 and 30 minutes after injection . Statistical data and results were studied using descriptive statistics as percentage and Mean ± SD . To compare the response to treatment , Mann – Whitney U-test was used in two groups . Consequently , the data were analyzed using the SPSS16 software . Results Pain score measured in two groups five minutes after the injection of lidocaine and morphine were 65 % and 53 % respectively ( 95 % CI 0.60 - 0.69 , CI 0.48 – 0.57 , p = 0.0002).108 ( 90 % ) patients ( 95 % CI 0.84 – 0.95 ) from group I and 84 ( 70 % ) patients ( 95 % CI 0.62 - 0.78 ) from group II responded appropriately at the end of the complete treatment . The difference was statistically significant ( p = 0.0001 ) . Conclusions Changing the smooth muscle tone and reducing the transmission of afferent sensory pathways , lidocaine causes a significant reduction in pain . Trial registration Clinical Trials I RCT Abstract Objective : To compare the efficacy and adverse effects of intramuscular etofenamate and intramuscular diclofenac in the relief of acute renal colic . Patients and methods : A multicentre , r and omised , single-blind study was performed in 119 patients admitted to the emergency room for renal colic . Patients were assigned to treatment with either etofenamate l000 mg or diclofenac 75 mg , both administered intramuscularly . Pain was self-assessed using a 4-point verbal rating scale ( VRS ) and a visual analogue scale ( VAS ) just before drug administration and 30 , 60 , 120 and 240 min later . Results : The two groups were similar with regard to baseline characteristics . The percentages of patients who reported an improvement in the VRS at 60 min post-administration ( primary variable ) were 84.5 % with etofenamate and 83.3 % with diclofenac ( p = 0.73 ) . At the other timepoints ( 30 , 120 and 240 min ) , the proportions of patients improved were , respectively , 69.5 % , 82.6 % and 79.3 % in the etofenamate group , and 75.0 % , 81.7 % and 80.0 % in the diclofenac group . The VAS score showed a statistically significant improvement in both groups , but no differences between groups were found . Analgesic rescue medication was required by 11 ( 18.6 % ) patients in the etofenamate group and by 12 ( 20.0 % ) patients in the diclofenac group . Mild to moderate adverse events were reported by 3.4 % of patients receiving etofenamate and by 5.0 % of patients receiving diclofenac . Conclusion : Etofenamate and diclofenac were similarly effective and tolerated in the relief of acute renal colic In this double blind , prospect i ve study , the relative efficacy of Diclofenac + Pitofenone + Fenpiverinium ( Manyana ) and Analgin + Pitofenone + Fenpiverinium ( Baralgan ) in 200 patients of biliary , ureteric and intestinal colic was evaluated . Patients were given these coded drugs thrice daily for five days starting from day 0 to day 5 . The results of the present clinical evaluation demonstrated that Manyana appeared to be superior to Baralgan in biliary and ureteric colic while it was therapeutically equivalent to Baralgan in reducing the pain intensity in intestinal colic . Both the medications were tolerated well and there were no side-effects reported PURPOSE Recent studies show the interesting efficacy of different drug combinations for the spontaneous expulsion of distal ureteral stones . We performed a r and omized , prospect i ve study to assess and compare the efficacy of 3 drugs as medical expulsive therapy for distal ureteral calculi . MATERIAL S AND METHODS A total of 210 symptomatic patients with distal ureteral calculi greater than 4 mm were r and omly allocated to home treatment with phloroglucinol , tamsulosin or nifedipine ( groups 1 to 3 , respectively ) . Each group was given a corticosteroid drug and antibiotic prophylaxis with an injectable nonsteroidal anti-inflammatory drug was also used on dem and . The primary end point was the expulsion rate and the secondary end points were expulsion time , analgesic use , need for hospitalization and endoscopic treatment as well as the number of workdays lost , quality of life and drug side effects RESULTS The expulsion rate was significantly higher in group 2 ( 97.1 % ) than in groups 1 ( 64.3 % , p < 0.0001 ) or 3 ( 77.1 % , p < 0.0001 ) . Group 2 significantly achieved stone passage in a shorter time than the other 2 groups and showed a significantly decreased number of hospitalizations as well as a better decrease in endoscopic procedures performed to remove the stone . The control of renal colic pain was significantly superior in group 2 compared with the other groups , result ing in fewer workdays lost . Group 3 showed lower analgesic use and decreased workdays lost compared with group 1 . No difference in side effects was observed among the groups . CONCLUSIONS Medical expulsive therapy should be considered for distal ureterolithiasis without complications before ureteroscopy or extracorporeal lithotripsy . The use of tamsulosin in this treatment regimen produced stone expulsion in almost all cases in a short time , allowing complete home patient treatment Forty-nine patients with ureteral colic were included in this prospect i ve double-blind study investigating the analgesic efficacy and side effects of a prostagl and in synthetase inhibitor Diclofenac sodium ( Voltaren ® ) versus a spasmolytic drug Tropenzilium bromide ( Palerol ® ) . The analgesic efficacy and side effects of the calcium antagonist Nifedipine ( Nidilat ® ) applied sublingually in ureteral colic were also investigated . It was concluded that diclofenac sodium was more efficient for relieving pain due to acute ureteral obstruction and had fewer side effects than spasmolytic drugs . Nifedipine proved to have an analgesic effect equivalent to that of Tropenziilium bromide Pain from ureteral stones is believed to be due to spasm and hyper-peristalsis of the involved ureter . Nifedipine has been shown to decrease human ureteral spasm in vitro . Conflicting results have been reported concerning the clinical efficacy of nifedipine in relieving acute renal colic . This prospect i ve , double-blind , crossover clinical trial evaluated the acute pain relief obtained in 30 patients who had ureteral stones . All patients had ureteral stones documented either by plain abdominal radiograph ( six ) , intravenous pyelogram ( 16 ) , or passage of the stone(s ) in the urine ( eight ) . Each patient served as his own control . The mean pain relief scores for placebo versus 10 to 20 mg oral nifedipine were 0.7 + /- 1.8 and 1.2 + /- 2.5 , respectively , as measured on a visual analogue scale ( P = .404 ) . Seven patients received clinical ly significant relief associated with nifedipine , and three patients received relief from placebo ( P = .300 ) . Twenty patients ( 66 % ) did not experience clinical ly significant relief from either treatment . We conclude that nifedipine does not differ significantly from placebo in providing relief from acute renal colic To assess the spasmolytic effect of drotaverine hydrochloride in colicky pain caused by renal and ureteric stones PURPOSE We determined whether the addition of hyoscine butylbromide ( Buscopan ) reduces the amount of opioid analgesia required and the need for ongoing opioid analgesia in acute renal colic . MATERIAL S AND METHODS Patients with a clinical diagnosis of acute renal colic were prospect ively r and omized to receive Buscopan or placebo in addition to morphine and intravenous fluids , with or without indomethacin . Observations and pain scores were recorded 15 every minutes during the first hour then hourly thereafter . Morphine was administered in 2.5 mg increments until pain relief was achieved . Recordings were ceased at 4 hours or on discharge from the emergency department , whichever occurred first . The diagnosis of renal colic was confirmed by computerized tomography . The dose of morphine ( mg/kg ) and the proportion of patients who required further morphine were compared between the 2 groups . RESULTS Of the 192 patients r and omized , data were available for 178 on an intent to treat basis . A total of 85 patients received Buscopan while 93 received placebo in addition to st and ard therapy . Patients in the Buscopan group required a median of 0.12 mg/kg of morphine while those in the placebo group received a median of 0.11 mg/kg , and this difference was not significant ( p = 0.4 ) . There was also no significant difference in the proportion of patients who required additional morphine , 33 % in the Buscopan group and 38 % in the placebo group ( p = 0.5 ) . Subgroup analysis of the 138 patients with a confirmed stone also showed no difference between the groups . CONCLUSIONS There is no evidence that Buscopan reduces opioid requirements or the need for ongoing opioid analgesia in acute renal colic STUDY OBJECTIVE To compare the analgesic efficacy and safety of IV ketorolac , the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute pain in the United States , with IV meperidine and with a combination of the two agents in renal colic . METHODS We carried out a double-blind , r and omized , multicenter clinical trial in the emergency departments of four urban tertiary care teaching hospitals . Our study subjects were 154 patients with suspected renal colic . Each subject received an initial IV dose of ketorolac 60 mg , meperidine 50 mg , or both supplemented as needed beyond 30 minutes with additional doses of meperidine . RESULTS The main outcome measures were changes in pain-intensity and pain-relief scores , amount of supplemental meperidine required , end-of- study drug tolerability , and adverse events . Analyses of 106 subjects with confirmed renal colic indicated that ketorolac and the combination were significantly better than meperidine alone by all efficacy measures , including pain relief and time elapsed before the need for supplemental meperidine . By 30 minutes , 75 % of the ketorolac group and 74 % of the combination group had a 50 % reduction in pain scores , compared with 23 % of the meperidine group ( P < .001 ) . The ketorolac and combination groups did not differ significantly in any of the efficacy measures . CONCLUSION IV ketorolac , alone or in combination with meperidine , was superior to IV meperidine alone in moderate and severe renal colic . Because many subjects in all three treatment groups received supplemental meperidine and because response to ketorolac alone can not be predicted , clinicians may choose to initiate treatment with a ketorolac-meperidine combination In a double-blind , double-dummy r and omized controlled clinical trial , the onset and duration of the analgesic effect of dipyrone , 1 or 2 g , and diclofenac sodium , 75 mg , by either the i.m . or the i.v . route were compared in 293 patients ( aged 18–70 years ) with acute renal colic . A level of ≥ 50 mm on the 100-mm visual analogue scale was required for inclusion in the study . Patients were r and omly allocated to six treatment groups , receiving dipyrone 1 g i.m . , dipyrone 1 g i.v . , dipyrone 2 g i.m . , dipyrone 2 g i.v . , diclofenac sodium 75 mg i.m . ; and diclofenac sodium 75 mg i.v , respectively . Evaluations were performed at 10 , 20 , 30 , and 60 min and 2 , 4 , and 6 h after treatment ( time 0 ) . Primary efficacy end points included course of pain , total pain , percentage of patients with a pain improvement of 50 % or more at each evaluation time , pain intensity evaluated by the investigator on a 0–3 scale , and differences in pain intensity . The analgesic response was more marked and prolonged among patients receiving dipyrone 2 g i.m . or dipyrone 2 g i.v . There were no significant differences between dipyrone 1 g and diclofenac sodium 75 mg , by either the i.m . or the i.v . route . All treatment regimens were well tolerated We have conducted a double-blind , r and omized , placebo-controlled trial with oral diclofenac to study the prophylactic effect on renal colic recurrence and spontaneous stone expulsion rate . Forty-one patients were given 50 mg oral diclofenac 3 times a day for 7 days after being discharged for a colic episode from Oslo Emergency Hospital ( < 24 h stay ) and 39 patients were given matching placebo tablets . The number of new renal colic episodes per accumulated patient treatment days was 64/287 in the diclofenac group and 119/273 in the placebo group ( p < 0.01 ) . This difference was greatest during the first 4 treatment days . A similar trend was found for pain intensity ( 0 - 10 cm VAS ) with the greatest difference on day 1 ( 4.3 vs. 2.8 , p = 0.05 ) . Side effects , mainly gastrointestinal , were reported for 14 % of the treatment days in both treatment groups . Stone expulsion rate was almost identical ( 28 vs. 29 days ) , regardless of stone size . Readmission rate to Oslo Emergency Hospital/other hospitals were 10 and 67 % ( p < 0.001 ) . In conclusion , oral treatment with diclofenac was effective as short-term prophylaxis of new colic episodes , especially during the first 4 days , and reduces the number of hospital readmissions significantly . The stone passage rate appears not to be affected A r and omised multicentre clinical trial was undertaken to compare the effect on pain of indomethacin administered either intravenously or rectally to 116 patients with ureteric colic . Adverse reactions were also assessed . Of the patients receiving the intravenous injection , 48/53 ( 91 % ) achieved good pain relief ( i.e. no supplementary analgesia was required ) 30 min after administration , compared with 46/63 ( 73 % ) receiving the enema . Significantly more side effects occurred in the group treated intravenously . It was concluded that indomethacin administered as an enema was less effective than the intravenous form , but it should be regarded as a good alternative in the treatment of ureteric colic PURPOSE We evaluate and compare the effectiveness of 2 different medical therapies during watchful waiting in patients with lower ureteral stones . MATERIAL S AND METHODS A total of 86 patients with stones less than 1 cm located in the lower ureter ( juxtavesical or intramural tract ) were enrolled in the study and were r and omly divided into 3 groups . Group 1 ( 30 ) and 2 ( 28 ) patients received daily oral treatment of 30 mg deflazacort , ( maximum 10 days ) . In addition group 1 patients received 30 mg nifedipine slow-release ( maximum 28 days ) and group 2 received 1 daily oral therapy of 0.4 mg tamsulosin ( maximum 28 days ) , Group 3 patients ( 28 ) were used as controls . Statistical analyses were performed using Student 's test , ANOVA test , chi-square test and Fisher 's exact test . RESULTS The average stone size for groups 1 to 3 was 4.7 , 5.42 and 5.35 mm , respectively , which was not statistically significant . Expulsion was observed in 24 of 30 patients in group 1 ( 80 % ) , 24 of 28 in group 2 ( 85 % ) and 12 of 28 in group 3 ( 43 % ) . The difference in groups 1 and 2 with respect to group 3 was significant . Average expulsion time for groups 1 to 3 was 9.3 , 7.7 and 12 days , respectively . A statistically significant difference was noted between groups 2 and 3 . Mean sodium diclofenac dosage per patient in groups 1 to 3 was 19.5 , 26 , and 105 mg , respectively . A statistical significant difference was observed between groups 1 and 2 with respect to group 3 . CONCLUSIONS Medical treatments with nifedipine and tamsulosin proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced need for analgesic therapy . Moreover medical therapy , particularly in regard to tamsulosin , reduced expulsion time A prospect i ve , r and omized , open-label , single-dose study was conducted in an emergency department ( ED ) of a tertiary care teaching hospital to evaluate the efficacy of hyoscyamine sulfate as compared to ketorolac tromethamine for the reduction of pain from ureteral colic in the ED . Patients were included if they were at least 18 years of age and presented to the ED with an initial history and physical examination consistent with ureteral colic . Ureteral calculi were confirmed by ultrasound or intravenous urogram . Consecutive patients were r and omized to either a single sublingual dose of 0.125 mg of hyoscyamine sulfate or a single intravenous dose of 30 mg of ketorolac tromethamine given over 1 minute . After 30 minutes , if analgesia was inadequate , patients were given rescue medication . Baseline pain scores were obtained using a horizontal , 100-mm visual analog scale . Additional pain scores were obtained at 10-minute intervals for 30 minutes . Upon completion of the study , both patients and physicians completed a global assessment score question naire . Fifty-four evaluable patients were r and omized . Demographics and baseline pain scores were similar for each group . Decreasing trends in pain over time were observed for both treatment groups , with significantly greater pain reduction observed with ketorolac tromethamine as compared to hyoscyamine sulfate . Global evaluations of pain relief revealed better results in the ketorolac tromethamine group than in the hyoscyamine sulfate group , although this result was not statistically significant A double-blind study was conducted to evaluate the efficacy , safety and usefulness of cimetropium bromide ( DA3177 ) in the patients with pain caused by upper urinary calculus at a daily dose of 75 mg t.i.d . ( Group D , 97 patients ) in comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d . ( Group B , 101 patients ) . According to patient 's impression , the rate of " moderately improved " or better was significantly higher in Group D ( 68.7 % ) than in Group B ( 53.5 % ; Wilcoxon 2 sample test : p = 0.0044 ) . For pain , the rate of " moderately improved " or better was 69.1 % in Group D and 60.4 % in Group B. In global improvement , the rate of " moderately improved " or better was significantly higher in Group D ( 70.1 % ) than in Group B ( 61.4 % ; Wilcoxon 2 sample test : p = 0.0469 ) . The rate of " no problem in safety " showed no significant difference between Group D ( 91.5 % ) and Group B ( 93.3 % ) . Adverse reactions occurred in 8.5 % in Group D and 6.7 % in Group B. The major adverse reactions were " dry mouth " , " abdominal distension " , " constipation " and " nausea " . The rate of " useful " or better was 68.7 % in Group D , and 60.4 % in Group B. In conclusion , DA3177 was confirmed to be a useful drug for patient with pain caused by upper urinary calculus A prospect i ve , r and omized , double-blind study was performed on 87 patients with ureterolithiasis , assessing the effect of the essential oil preparation Rowatinex ( Rowa Pharmaceuticals , Irel and ) for the treatment of ureterolithiasis . Forty-three patients were treated with Rowatinex and 44 patients with placebo . Despite the larger average diameter of calculi in the group of patients treated with Rowatinex , the overall stone expulsion rate was significantly higher in the Rowatinex group as compared to placebo : 81 % and 59 % , respectively ( 0.025 > p > 0.01 ) . This higher rate of stone expulsion is observed in patients with disappearance of pretreatment ureteral dilatation ( when patients with expelled stones are excluded ) ( 0.05 > p > 0.001 ) . Seven patients in the Rowatinex group had mild to moderate gastrointestinal disturbances ; no other significant side effects were noted during the treatment in either group . We conclude that early treatment with Rowatinex for patients with ureteral stones is indicated before other more aggressive measures are considered BACKGROUND AND PURPOSE Although the continuous perfusion of antispasmodic drugs has been the traditional mainstay in the treatment of renal colic , the results more often than not are unsatisfactory . Our hypothesis was that a continuous intravenous ( IV ) drip of tramadol would be an effective and safe alternative . PATIENTS AND METHODS In this prospect i ve study , 300 patients with renal colic were r and omized into four treatment groups , single blind for the patients . At the start , all received an anti-inflammatory drug intramuscularly and an antiemetic and antispasmodic IV . Group A was given the classical IV antispasmodic perfusion combined with a sham drip . Group B received the classical antispasmodic perfusion in combination with a tramadol drip . Group C had a sham perfusion and drip . Group D received a sham perfusion and tramadol drip . There was no significant difference in the degree of pain between the groups on a visual analog scale ( VAS ) at the start . The pain was scored again on the VAS at 30 minutes , 1 hour , and 4 hours after the start of the treatment and at IV urography . Side effects , as well as the need for rescue medication , were registered . RESULTS Both tramadol groups scored significantly better after 60 and 240 minutes and during IV urography ( P < 0.005 ) . There was a significant decrease in VAS in group B after 30 minutes . The tramadol groups needed significantly less rescue medication ( P = 0.001 ) . There was no significant difference in the reported side effects . The combination spasmolytic-tramadol drip scored the best , although the difference was not statistically significant . CONCLUSION We consider our hypothesis proved that a continuous tramadol drip is a safe and valuable analgesic regimen in renal colic Ureteral colic occurs in 24 to 34 per cent of all patients following extracorporeal shock wave lithotripsy . Recent research has shown prostagl and in synthetase inhibitors to be effective in relieving the pain associated with ureteral colic . Our prospect i ve , controlled , double-blind , r and omized study was design ed to test the efficacy of indomethacin in the prophylactic treatment of pain after extracorporeal shock wave lithotripsy . Patients undergoing extracorporeal shock wave lithotripsy were r and omized into 2 groups . Group 1 received 100 mg . indomethacin suppositories twice daily and group 2 received placebo suppositories . After extracorporeal shock wave lithotripsy 2 analgesics were available to the patients : oral co-dydramol or intramuscular pethidine was offered in the normal manner by the nursing staff . The pre-extracorporeal shock wave lithotripsy x-ray was used to make a quantitative estimate of the total stone burden in each patient . The post-extracorporeal shock wave lithotripsy analgesic requirement was used to compare the 2 groups . Of 112 patients recruited to the study 55 received indomethacin and 57 received placebo . The request for analgesia in the 2 groups was not different ( 28 of 55 and 33 of 57 , respectively ) . However , in the indomethacin group only 6 patients required pethidine ( 10 doses ) , compared to 18 ( 41 doses ) in the placebo group . This difference is statistically significant ( p less than 0.01 ) . There was no difference between the 2 groups in the occurrence of ureteral steinstrasse . Indomethacin has been shown to be effective in the prophylactic treatment of ureteral colic after lithotripsy PURPOSE We tested whether paracetamol could improve pain relief in patients visiting the emergency department with acute renal colic as compared to piroxicam , a nonsteroidal anti-inflammatory drug ( NSAID ) . MATERIAL S AND METHODS Patients with a diagnosis of acute renal colic were prospect ively r and omized to receive either intravenous paracetamol ( 1 g ) or intramuscular piroxicam ( 20 mg ) . We monitored patients for visual analog scale ( VAS ) , heart rate , arterial blood pressure , need for rescue therapy , and adverse events at different time points for 90 minutes . We recorded admission requirement and new visit for renal colic at 72 hours . The primary end point was pain relief at 90 minutes , defined as a decrease of 50 % or more as compared to the initial VAS . The secondary objectives were comparison of the 2 groups for VAS at any time points and the occurrence of adverse events . RESULTS Of the 226 eligible patients , 100 entered the study . Fifty patients received paracetamol and 50 received NSAID . Pain relief at 90 minutes was obtained in 40 patients receiving paracetamol ( 80 % ) and 24 ( 48 % ) receiving NSAID ( P = .002 ) . Visual analog scale was lower in the paracetamol group since 45 minutes . Only 2 adverse events were observed . CONCLUSION A single therapy with intravenous paracetamol more efficiently relieved pain in acute renal colic than did intramuscular piroxicam BACKGROUND Many drugs have been utilized for the treatment of renal colic , but to date no drugs that relieve pain quickly and completely have been developed . Thus , we conducted a prospect i ve trial to evaluate the effects of trigger point injection on renal colic . In this study , we used a local injection of lidocaine to the trigger point of patients experiencing renal colic , and evaluated the efficacy in patients using the visual analog scale . METHODS Sixty patients with renal colic were enrolled in this study and divided into two groups by a simple r and omization : ( i ) the butylscopolamine group ( n = 30 , intravenous injection of butylscopolamine bromide and sulpyrine ) ; and ( ii ) the lidocaine group ( n = 30 , local anesthesia to the trigger point with lidocaine ) . RESULTS Renal colic had disappeared completely at the end of the trigger point injection in 15/30 patients and the average time required to produce a 50 % improvement in symptoms was 9 min in all patients in the group . In the lidocaine group , only one patient needed an additional anodyne treatment after 60 min and none of the 29 patients whose pain disappeared within 60 min needed further anodyne treatment within 24 h. These results were all significantly superior to those of the conventional treatment . No side-effects and complications were observed . CONCLUSION Trigger point injection , in our experience , is an easy , safe and effective method for the amelioration of renal colic . It was significantly superior to the combination of intravenous butylscopolamine and sulpyrine OBJECTIVES To evaluate the effectiveness of medical therapy during watchful waiting in patients with distal ureter stones . METHODS Ninety-six patients with radiopaque stones located in the distal tract of the ureter and with stone sizes of 1 cm or smaller were involved in the study . The patients were r and omly divided into two groups . Group A ( n = 48 ) received oral treatment with 30 mg of deflazacort daily ( maximum 10 days ) plus 30 mg of slow-release nifedipine daily ( maximum 4 weeks ) . Group B ( n = 48 ) underwent a wait- and -watch approach . Both groups of patients were allowed to use diclofenac on dem and . Statistical analyses were carried out using Student 's t test , the chi-square test , and Fisher 's exact test . RESULTS The average stone size was 5.8 + /- 1.8 mm for group A and 5 . 5 + /- 1.4 mm for group B. No statistically significant difference was found in stone size . Stone expulsion was observed in 38 ( 79 % ) of 48 patients in group A and in 17 ( 35 % ) of 48 patients in group B. The average expulsion time was 7 days ( range 2 to 10 ) for group A and 20 days ( range 10 to 28 ) for group B. A statistically significant difference was observed in both the expulsion rate and the expulsion time ( P < 0.05 ) . The mean amount of sodium diclofenac used was 15 mg per patient for group A and 105 mg per patient for group B ( P < 0.05 ) . CONCLUSIONS The medical treatment proved to be effective and safe , as demonstrated by the increased stone expulsion rate , decreased expulsion time , and reduced need for analgesic therapy BACKGROUND : Patients with acute renal colic usually require immediate diagnosis and treatment . In this clinical trial analgesic effect of hyoscine N-butyl bromide and desmopressin combination in comparison with hyoscine N-butyl bromide alone in patients with acute renal colic induced by urinary stones was assessed . METHODS : The study included 114 patients r and omly allocated in two groups ( A and B ) . Patients in group A received 20 mg intramuscular hyoscine N-butyl bromide at admission time and patients in group B received 20 μg of intranasal desmopressin in combination with 20 mg intramuscular hyoscine N-butyl bromide . A visual analogue scale ( VAS ; a 10-cm horizontal scale ranging from “ zero or no pain ” to “ 10 or unbearable pain ” ) was hired to assess the patients ’ pain severity at baseline , 30 and 60 minutes after the treatments . RESULTS : On admission , the pain level was similar in both groups ( group A : 8.95 ± 0.11 and group B : 8.95 ± 0.12 ) . In group A , the mean of pain level showed a decrease after 30 minutes ( group A : 7.26 ± 0.25 and group B : 5.95 ± 0.28 ) but further decreasing did not occur ; however in group B , the pain consistently decreased and the mean after 60 minutes was significantly decreased ( group A : 6.80 ± 0.31 and group B : 3.71 ± 0.31 ) . No side effects were detected in this study . CONCLUSIONS : The combination of hyoscine N-butyl bromide and desmopressin is more effective than hyoscine N-butyl bromide alone in patients with renal colic . Further studies are recommended to vali date these findings and compare the different doses of desmopressin A double blind r and omized study was conducted in 52 patients with renoureteric colic to compare the therapeutic efficacy of two analgesics given in a single intramuscular dose . Following the administration of 2 gm dipirone plus 20 mg hyoscine N-butylbromide ( n = 26 ) or 150 mg flurbiprofen ( n-26 ) , the patients were assessed for pain intensity , relief and pain status for a period of one hour . Both treatments afforded a similar analgesic effect , with pain remitting in 76.9 % of the cases . No significant differences were observed for the latency periods or degree of pain at 5 , 10 , 30 and 60 minutes following treatment . Additional analgesic therapy was required in 34.6 % of the patients who received dipirone and 26.9 % of the flurbiprofen group , the difference not being statistically significant . Overall both drugs were well tolerated and only local adverse effects were observed , pain being the most frequent 31 patients with symptoms of acute renal colic were treated with diclofenac natrium . According to preliminary results this drug is more effective for relieving pain of acute renal colic than the traditional combination of spasmolytics and analgetics . This might be due to the blocking effect of diclofenac natrium on the renal PG synthesis and release , thus decreasing the diuresis . Side effects were minimal , as nausea , vomiting etc . Authors highly recommend this drug as the first choice of treatment in acute renal colic OBJECTIVE To assess the possible therapeutic effect of 40 mg sublingual piroxicam ( fast-dissolving dosage form , FDDF ) compared with intramuscular 75 mg diclofenac , as a reference drug , on acute renal colic in a r and omized , double-blind controlled clinical trial . PATIENTS AND METHODS Eighty patients were assigned to one of two treatment groups ; one received an intramuscular injection with 0.2 mL distilled water and two sublingual tablets of 20 mg piroxicam FDDF , and the other received an intramuscular injection with 75 mg diclofenac sodium and two sublingual tablets of placebo . Pain intensity was evaluated by the patient using a visual analogue scale and by the observers . Vital signs at baseline and 30 min after the administration of the study drugs were also recorded . RESULTS The overall efficacy of the treatment was 81 % ; nine patients in the piroxicam and six in the diclofenac group ( no significant difference ) required rescue treatment . Compared with baseline levels , the pain relief was significant ( P < 0.001 ) at 30 min in both groups . Twenty-two patients in the piroxicam and 25 in the diclofenac group attained complete pain relief at 30 min , as evaluated by the observer ( no significant difference ) . Both treatments were similarly effective in decreasing vital signs , mainly systolic blood pressure , heart and respiratory rates . However , when the percentage change was compared between the groups , piroxicam significantly decreased the respiratory rate ( P < 0.03 ) . CONCLUSION Piroxicam FDDF is as effective as parenteral diclofenac in emergency renal colic treatment . Furthermore , its ease of self-administration increases patient compliance and potential use in general practice Abstract Ureteric obstruction causes increased synthesis and release of prostagl and ins . As a result renal pelvic pressure rises , causing renal colic . This double-blind study in 66 patients with acute renal colic shows that intramuscular injection of a potent prostagl and in-synthetase inhibitor ( diclofenac sodium ) is more effective and has fewer side-effects than a narcotic drug commonly used to treat ureteric colic We have conducted a double-blind r and omised placebo controlled trial with oral diclofenac to study the prophylactic effect on recurrence of renal colic and rate of spontaneous stone expulsion . 41 patients were given 50 mg oral diclofenac three times a day for seven days after being discharged for a colic episode from Oslo Emergency Hospital and 39 patients were given matching placebo tablets . The number of new ureteral colic episodes per accumulated patient treatment days was 64/287 in the diclofenac group and 119/273 in the placebo group ( p < 0.01 ) . The difference was greatest during the first four days of treatment . A similar trend was found for pain intensity , with the greatest difference on day one . There was no difference in reported type or frequency of side effects in the two treatment groups . Stone expulsion rate was almost identical . The effect of the treatment was not affected by fluid intake . Re-admission rates to Oslo Emergency Hospital or other hospitals were 10 and 67 % ( p < 0.001 ) Summary A r and omized , double-blind clinical trial in 50 patients was done to compare the efficacy and tolerance of single doses of intramuscular diclofenac 75 mg and dipyrone 2 g in acute renal colic . Both drugs were equally effective , but diclofenac was better in terms of complete relief of pain . Vital signs were affected according to the stress and pain PURPOSE We tested whether the addition of phloroglucinol to piroxicam could improve pain relief in patients with acute renal colic visiting the emergency department . MATERIAL S AND METHODS Patients with a diagnosis of acute renal colic were prospect ively r and omized to receive intravenous phloroglucinol ( 200 mg ) or placebo combined with intramuscular piroxicam ( 20 mg ) . We monitored the visual analogic scale ( VAS ) , heart rate , arterial blood pressure , need for rescue therapy , and adverse events at different time points for 1 hour . We recorded admission requirement and new visit at 72 hours for renal colic . The primary end point was to assess pain relief at 1 hour , defined as a decrease of 50 % or more as compared with the initial VAS . The secondary objectives were to compare the 2 groups for VAS at any time points , the need for rescue therapy , and the occurrence of adverse events . RESULTS Of the 309 eligible patients , 253 entered the study . A total of 126 patients received phloroglucinol and 127 patients received placebo . Pain relief at 1 hour was obtained in 89 patients ( 71 % ) receiving phloroglucinol and 89 patients ( 70 % ) receiving placebo ( P = .89 ) . There were no differences in VAS between the 2 groups at any time points . Rescue therapy was required in 37 patients ( 29 % ) receiving phloroglucinol and 38 patients ( 30 % ) receiving placebo ( P = .51 ) . Number of adverse events was similar with phloroglucinol and placebo : 20 ( 16 % ) and 16 ( 13 % ) , respectively ( P = .44 ) . CONCLUSIONS There was no evidence that the addition of phloroglucinol improved the efficiency of piroxicam to relieve pain in acute renal colic PURPOSE Although non-selective non-steroidal anti-inflammatory drugs ( nsNSAIDs ) and opioids are effective treatments for acute renal colic , they are associated with adverse events ( AEs ) . As cyclooxygenase-2 selective NSAIDs may provide a safer alternative , we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic . MATERIAL S AND METHODS Phase IV . , multicenter , double-blind , noninferiority , active-controlled study : 338 subjects with acute renal colic were r and omized to parecoxib 40 mg i.v . plus placebo ( n = 174 ) or ketoprofen 100 mg IV plus placebo ( n = 164 ) . 338 subjects with acute renal colic were r and omized to parecoxib 40 mg IV ( n = 174 ) or ketoprofen 100 mg IV(n = 164 ) plus placebo . Subjects were evaluated 15 , 30 , 45 , 60 , 90 and 120 minutes after treatment start and 24 hours after discharge . Primary endpoint was the mean pain intensity difference ( PID ) at 30 minutes by visual analog scale ( VAS ) ( per- protocol population ) . An ANCOVA model was used with treatment group , country , and baseline score as covariates . Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95 % confidence interval ( CI ) for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint . RESULTS Baseline demographics were similar . The mean ( SD ) mPID30 min was 33.84 ( 24.61 ) and 35.16 ( 26.01 ) for parecoxib and ketoprofen , respectively . For treatment difference ( parecoxib-ketoprofen ) the lower bound of the 95 % CI was 6.53 . The mean change from baseline in VAS 30 minutes after study medication was ~43 mm ; AEs were comparable between treatments . CONCLUSIONS Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic , is well tolerated , and has a comparable safety profile A r and omized prospect i ve double-blind study of the analgesic effect of 50 mg . intravenous indomethacin , a prostagl and in synthesis inhibitor , was done on 47 consecutive patients with acute ureteral colic . The placebo used was 5 mg . intravenous riboflavin because of the same color as indomethacin . Indomethacin provided complete relief in 78 per cent of the cases , while riboflavin provided relief in 30 per cent . The difference is statistically significant . No side effects were observed with indomethacin A single-blind , r and omized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium ( 75 mg ) versus a dipyrone ( 1 g)/spasmolytics combination , and diclofenac sodium ( 75 mg ) versus pethidine ( 75 mg ) . The first study involved three centres , the second study one centre . In total , 107 patients were treated with diclofenac sodium , 85 with dipyrone/spasmolytics , and 25 with pethidine . Assessment s were made during the first hour after drug administration of the degree of pain relief , the severity of pain using a visual analogue scale , and the duration of analgesia . A global assessment of treatment efficacy was made by the participating physicians at the end of the study period . Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine . Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group , a significantly longer effect was seen when diclofenac sodium was compared with pethidine ( p less than 0.01 ) . Pain severity assessment s revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics ( p less than 0.05 ) and after 30 minutes compared to pethidine ( p less than 0.05 ) . Global efficacy assessment s by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics ( p less than 0.01 ) and pethidine ( p less than 0.001 ) . Moreover , diclofenac sodium was better tolerated than either of the comparative treatments . The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic Objectives To assess the efficacy of desmopressin nasal spray compared with diclofenac given intramuscularly in patients with acute renal colic caused by urolithiasis In a prospect i ve , r and omized study , the prophylactic effect of indomethacin ( 150 mg daily ) in regard to recurrence of ureteral colic was investigated in 78 patients . Severe recurrent attacks were experienced in 78 patients . Severe recurrent attacks were experienced by 4 of 37 patients in the test group and by 16 of the 41 controls without indomethacin . The mean duration of recurrent pain including the severe attacks was 5.6 + /- 1.1 hour/patient/week in the test group and 12.5 + /- 2.9 in the control group . Passage of stone within 7 days was not influenced by indomethacin ( 22/37 and 25/41 cases ) . Indomethacin administration for 7 days after an acute attack of ureteral colic thus reduced the frequency of severe attacks and the total duration of recurrent pain , without influencing the stone passage The analgesic efficacy and safety of parenteral butorphanol and meperidine were compared . The double-blind , r and omized study involved 120 patients presenting with moderate to severe renal colic . Pain intensity and pain relief were evaluated by trained observers at fixed time intervals for four hours after study drug was administered . Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy . Butorphanol 4 mg was significantly more effective than butorphanol 2 mg and was equivalent to meperidine 80 mg . Overall efficacy assessment s were " good " or " excellent " for 87 per cent , 72 per cent , and 85 per cent , respectively . There were no significant differences in side effects among treatment groups in the 83 evaluable and 27 inevaluable patients receiving study drugs . Butorphanol was effective and well-tolerated in this patient population , with important advantages over opiate analgesics A multicentric r and omised and prospect i ve study on conservative treatment of ureteric calculi had been performed . The frequency and transit time of spontaneously passing of the stones , side effects and cost of treatment have been compared under classic spasmoanalgetic therapy and a phytotherapeutic medicament ( Urol ) . In the group with spasmoanalgetic therapy 85.5 % of the stones passed spontaneously , in the group with Urol medication 89.3 % of the stones . There was no significant difference concerning the transit time of stones between the two groups , but side effects and costs were less in the Urol-group A r and omized prospect i ve double-blind study of the analgesic effect of 75 mg intramuscular diclofenac sodium ( Voltaren ® ) , a potent prostagl and in synthetase inhibitor , versus placebo ( saline solution ) was carried out in 131 consecutive patients with acute ureteral colic . Diclofenac provided complete relief of pain 25 minutes after the injection in 59 % of the cases , while placebo provided relief in 29 % ( p < 0·01 ) . Forty patients in the placebo group and seventeen patients in the diclofenac group needed an open injection of 75 mg diclofenac intramuscularly after 25 minutes due to persistent pain . Fifty-four of the fifty-seven patients treated with an open injection of diclofenac achieved complete relief of pain after 30 minutes . There were no side-effects of the treatment Abstract Objective : To compare the efficacy and adverse effects of ketorolac and diclofenac in the treatment of renal colic . Methods : In a double-blind , r and omized clinical trial , 57 patients admitted to the emergency room for renal colic , received either 30 mg of ketorolac or 75 mg of diclofenac i.m . ( intramuscularly ) . Evaluations were performed at 1 , 2 h and 6 h after treatment . Pain was assessed by a four-point verbal rating scale ( VRS ) and a visual analogue scale ( VAS ) . Only patients with at least moderate pain according to the VRS were included . Seventy-five milligrams of pethidine i.m . was given as rescue medicine , if insufficient analgesia was achieved . The adverse effects recorded were sedation , nausea and vomiting . Results : There was no significant difference between ketorolac and diclofenac , with respect to pain level over time , the number of patients requiring rescue medicine , or the level of adverse effects . Conclusion : Ketorolac and diclofenac are equally effective in the treatment of renal colic In an open , prospect i ve , r and omized study , the quality and duration of analgesia and the side effects associated with tramadol were compared with those of metimazole in acute ureteral colic in 60 patients . The results revealed that tramadol ( 100 mg ) is as effective as metimazole ( 2.5 g ) with respect to analgesia . No serious side effects were observed in either group PURPOSE We assessed the efficacy of papaverine hydrochloride , a commonly used smooth muscle relaxant , for the treatment of renal colic as a single agent and in combination with sodium diclofenac . MATERIAL S AND METHODS A prospect i ve , single-blind clinical study was performed at 2 centers . A total of 86 patients with acute renal colic were r and omized to 3 treatment groups of 120 mg intravenous papaverine hydrochloride ( 29 ) , 75 mg intramuscular sodium diclofenac ( 30 ) , and papaverine hydrochloride plus sodium diclofenac ( 27 ) . Pain intensity was assessed with the Visual Analog Scale at 0 , 20 and 40 minutes after treatment . Further analgesia given at patient request consisted of 1 mg/kg intramuscular meperidine . Urinalysis , complete blood evaluation and imaging were performed in all patients . All adverse effects were recorded . RESULTS Baseline characteristics were similar in the 3 groups . Pain intensity decreased significantly ( p < 0.01 ) after 20 and 40 minutes in all groups . Papaverine hydrochloride was as effective as sodium diclofenac in alleviating pain and the combined treatment group showed a slight trend of more rapid relief . Significantly more patients in the papaverine group required further analgesia and 4 patients ( 14.8 % ) reported minor adverse effects ( dizziness in 3 , sleepiness in 1 ) . CONCLUSIONS Papaverine hydrochloride is as effective as sodium diclofenac for the short-term relief of acute renal colic pain and may be advantageous in patients with contraindications for nonsteroidal anti-inflammatory drugs . However , sodium diclofenac appears to provide a longer effective analgesia OBJECTIVES To evaluate the efficacy of celecoxib as an analgesic and medical expulsive agent in acute renal colic . METHODS A prospect i ve r and omized double-blind study was conducted on patients presenting with an obstructing ureteral calculus < 10 mm in largest diameter . Patients were r and omized to 400 mg of celecoxib , followed by 200 mg every 12 hours for 10 days , or to placebo . Patients with a solitary kidney , renal insufficiency ( CR > 1.8 ) , urinary tract infection , or significant cardiovascular disease were excluded . RESULTS A total of 57 patients provided consent of which 53 completed the study . Four patients were excluded from the analysis because of stone passage or withdrawal of consent before the first dose of study medication . No significant difference was noted in the spontaneous stone passage rate ( celecoxib 55.2 % , placebo 54.2 % ) and between celecoxib and placebo with regard to days to stone passage ( 7.0 vs 9.0 , P = .6 ) or size of stone passed ( 3.9 vs 4.6 mm , P = .18 ) . No significant difference was noted in pain analog scores ( 2.6 vs 3.5 , P = .71 ) or narcotic doses ( 13.2 vs 13.6 , P = .74 ) . Furthermore , a 25 % decrease in narcotic use ( or 19 mg based on placebo mean ) was outside the 80 % one-sided confidence interval for the change in mean narcotic use between the 2 groups . Thus , it is unlikely ( < 20 % ) that we missed a clinical ly significant beneficial effect of celecoxib on narcotic consumption because of sample size . CONCLUSIONS Celecoxib does not facilitate stone passage or decrease narcotic requirements in patients with acute renal colic Pain owing to acute ureteral obstruction seems to be related closely to tension in the walls of the renal pelvis . Renal prostagl and ins are involved intimately in the events leading to the pain . A prostagl and in-synthetase inhibitor , diclofenac sodium , was used in the treatment of acute ureteral pain , and was compared to the traditional treatment of a combination of spasmolytic and narcotic drugs . Also , the need for overhydration as part of the management was tested . The 91 patients entered into the prospect i ve r and omized trial were divided into groups . Diclofenac sodium had a 90 per cent success rate in relieving pain at 30 minutes , and the combination of pethidine and hyoscine butyl bromide had a statistically higher success rate at 97.5 per cent ( p equals 0.05 ) . However , the latter therapy had a higher rate of side effects ( p equals 0.01 ) . There was no difference in the response between the groups in relation to whether they received intravenous fluids A r and omized multicenter clinical trial was design ed to compare the efficacy and tolerance of two different intramuscular doses of dipyrone ( 1 g and 2 g ) with those of the reference drug , diclofenac sodium ( 75 mg ) , in the treatment of acute renal colic . A total of 129 patients were included ; 43 patients were alloted to receive dipyrone 1 g , 45 to dipyrone 2 g , and 41 to diclofenac . Evaluation of pain ( 100 mm visual analogue scale ) was carried out at 10 , 20 , 30 , 60 min and 2 , 4 and 6 h after drug administration . There were no significant differences between the three groups in terms of pain relief in the first 60 min , but dipyrone 2 g provided significantly more pain relief than diclofenac and dipyrone 1 g from 60 min to 6 h after drug injection . It is concluded that dipyrone 2 g produced a longer lasting analgesic response than dipyrone 1 g in the treatment of renal colic PURPOSE alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones . We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose . MATERIAL S AND METHODS A total of 114 patients between 18 and 65 years old who had lower ureteral stones were included in the study . Patients were r and omly divided into 4 groups . Group 1 consisted of 28 patients and acted as the control group . Group 2 comprised 29 patients who received tamsulosin , group 3 was 28 patients receiving terazosin and group 4 was 29 patients receiving doxazosin . These agents were given for up to a month and hydration was also recommended simultaneously . Every week patients were controlled with x-rays of the kidneys , ureters , bladder and urinary ultrasonography . Meanwhile the number of pain episodes , analgesic dosage and the number of days for spontaneous passage of the calculi through the ureter were also recorded . RESULTS There were no differences between the groups with respect to age , weight , height , sex and stone size . The calculi passed through the ureter spontaneously in 15 patients in group 1 ( 53.57 % ) , in 23 patients in group 2 ( 79.31 % ) , in 22 patients in group 3 ( 78.57 % ) , and in 22 patients in group 4 ( 75.86 % ) . In groups 2 to 4 the number of pain episodes , expulsion time and analgesic dosage were found to be lower compared with those in group 1 . CONCLUSIONS alpha1-Adrenergic blockers increase the frequency of spontaneous passage of the distal ureteral calculi . All 3 agents tested were equally efficacious PURPOSE We evaluated the efficacy of the alpha1-adrenergic antagonist tamsulosin for conservative expulsive therapy in patients with ureteral colic due to juxtavesical stones . MATERIAL S AND METHODS A total of 60 consecutive symptomatic patients with stones located in the juxtavesical tract of the ureter were r and omly divided into group 1 - -30 who received oral floroglucine-trimetossibenzene 3 times daily and group 2 - -30 who received 0.4 mg tamsulosin daily . The 2 groups received 30 mg deflazacort daily for 10 days plus cotrimoxazole 2 times daily for 8 days and 75 mg diclofenac injected intramuscularly on dem and . Ultrasound followup and medical visits were performed weekly for 4 weeks . Stone passage rate and time , analgesic use , hospitalization and endoscopical intervention were evaluated . Statistical analysis was performed using the Student t test . RESULTS The stone expulsion rate was 70 % for group 1 and 100 % for group 2 . Mean stone size was 5.8 and 6.7 mm , respectively ( p = 0.001 ) . Mean expulsion time was 111.1 hours for group 1 and 65.7 hours for group 2 ( p = 0.020 ) . The mean number of diclofenac injections was 2.83 for group 1 and 0.13 for group 2 ( p < 0.0001 ) . Ten group 1 patients were hospitalized , of whom 9 underwent ureteroscopy , compared with none in group 2 ( p < 0.0001 and 0.001 , respectively ) . CONCLUSIONS Tamsulosin used as a spasmolytic drug during renal colic due to juxtavesical calculi increased the stone expulsion rate and decreased expulsion time , the need for hospitalization and endoscopic procedures , and provided particularly good control of colic pain In a study of the pain-relieving effect of 3 drugs commonly used to treat acute renal colic in this hospital , intravenous indomethacin and intramuscular diclofenac ( prostagl and in synthetase inhibitors ) were compared with intravenous Avafortan ( analgesic antispasmodic ) . As first-line analgesics , prostagl and in synthetase inhibitors , if given intravenously , offer an effective alternative to Avafortan . Of 145 patients studied , 32 required a second injection for complete relief of pain . Administering a second dose of prostagl and in synthetase inhibitors result ed in equally significant pain relief rate even though the route was intramuscular STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
11,251 | 31,745,841 | In this meta- analysis and systematic review , our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality | Recently , several studies have demonstrated that heart failure ( HF ) may increase the risk of incident cancer .
However , this association has not been statistically and systematic ally verified by any comprehensive pooled analyses .
We performed a meta- analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer . | Background : Heart failure ( HF ) survival has improved , and nowadays , many patients with HF die of noncardiac causes , including cancer . Our aim was to investigate whether a causal relationship exists between HF and the development of cancer . Methods : HF was induced by inflicting large anterior myocardial infa rct ion in APCmin mice , which are prone to developing precancerous intestinal tumors , and tumor growth was measured . In addition , to rule out hemodynamic impairment , a heterotopic heart transplantation model was used in which an infa rct ed or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ . After 6 weeks , tumor number , volume , and proliferation were quantified . C and i date secreted proteins were selected because they were previously associated both with ( colon ) tumor growth and with myocardial production in post – myocardial infa rct ion proteomic studies . Myocardial gene expression levels of these selected c and i date s were analyzed , as well as their proliferative effects on HT-29 ( colon cancer ) cells . We vali date d these c and i date s by measuring them in plasma of healthy subjects and patients with HF . Finally , we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large , prospect i ve general population cohort . Results : The presence of failing hearts , both native and heterotopically transplanted , result ed in significantly increased intestinal tumor load of 2.4-fold in APCmin mice ( all P<0.0001 ) . The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016 , respectively ) . We identified several proteins ( including serpinA3 and A1 , fibronectin , ceruloplasmin , and paraoxonase 1 ) that were elevated in human patients with chronic HF ( n=101 ) compared with healthy subjects ( n=180 ; P<0.001 ) . Functionally , serpinA3 result ed in marked proliferation effects in human colon cancer ( HT-29 ) cells , associated with Akt-S6 phosphorylation . Finally , elevated cardiac and inflammation biomarkers in apparently healthy humans ( n=8319 ) were predictive of new-onset cancer ( n=1124 ) independently of risk factors for cancer ( age , smoking status , and body mass index ) . Conclusions : We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors . A diagnosis of HF may therefore be considered a risk factor for incident cancer INTRODUCTION From a prospect i ve multicentre multicountry clinical trial , we developed and vali date d risk models to predict prospect i ve all-cause mortality and hospitalizations because of heart failure ( HF ) in patients with HF . METHODS AND RESULTS BIOSTAT-CHF is a research programme design ed to develop and externally vali date risk models to predict all-cause mortality and HF hospitalizations . The index cohort consisted of 2516 patients with HF from 69 centres in 11 European countries . The external validation cohort consisted of 1738 comparable patients from six centres in Scotl and , UK . Patients from the index cohort had a mean age of 69 years , 27 % were female , 83 % were in New York Heart Association ( NYHA ) class II-III and the mean left ventricular ejection fraction ( LVEF ) was 31 % . The full prediction models for mortality , hospitalization owing to HF , and the combined outcome , yielded c-statistic values of 0.73 , 0.69 , and 0.71 , respectively . Predictors of mortality and hospitalization owing to HF were remarkably different . The five strongest predictors of mortality were more advanced age , higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide , lower haemoglobin , and failure to prescribe a beta-blocker . The five strongest predictors of hospitalization owing to HF were more advanced age , previous hospitalization owing to HF , presence of oedema , lower systolic blood pressure and lower estimated glomerular filtration rate . Patients from the validation cohort were aged 74 years , 34 % were female , 85 % were in NYHA class II-III , and mean LVEF was 41 % ; c-statistic values for the full and compact model were comparable to the index cohort . CONCLUSION A small number of variables , which are usually readily available in the routine clinical setting , provide useful prognostic information for patients with HF . Predictors of mortality were remarkably different from predictors of hospitalization owing to HF BACKGROUND Several recent studies have suggested an increased cancer risk among patients with heart failure ( HF ) . However , these studies are constrained by limited size and follow-up , lack of comprehensive data on other health attributes , and adjudicated cancer outcomes . OBJECTIVES This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality . METHODS The study assembled a cohort from the Physicians ' Health Studies I and II , 2 r and omized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011 , respectively , that included annual health evaluations and determination of cancer and HF diagnoses . In the primary analysis , the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer , modeling HF as a time-varying exposure . In a complementary analysis , the study used the l and mark method and identified cancer-free participants at 70 years of age , distinguishing between those with and without HF , and likewise performed Cox regression . Sensitivity analyses were performed at 65 , 75 , and 80 years of age . RESULTS Among 28,341 Physicians ' Health Study participants , 1,420 developed HF . A total of 7,363 cancers developed during a median follow-up time of 19.9 years ( 25th to 75th percentile : 11.0 to 26.8 years ) . HF was not associated with cancer incidence in crude ( hazard ratio : 0.92 ; 95 % confidence interval : 0.80 to 1.08 ) or multivariable-adjusted analysis ( hazard ratio : 1.05 ; 95 % confidence interval : 0.86 to 1.29 ) . No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment . Results were similar when using the l and mark method at all l and mark ages . CONCLUSIONS HF is not associated with an increased risk of cancer among male physicians BACKGROUND Heart failure ( HF ) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized . The authors previously described an increased risk of cancer among HF patients compared with community controls . OBJECTIVES This study examined whether HF was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infa rct ion ( MI ) survivors . METHODS A prospect i ve cohort study was conducted among Olmsted County , Minnesota , residents with incident MI from 2002 to 2010 . Patients with prior cancer or HF diagnoses were excluded . RESULTS A total of 1,081 participants ( mean age 64 ± 15 years ; 60 % male ) were followed for 5,327 person-years ( mean 4.9 ± 3.0 years ) . A total of 228 patients developed HF , and 98 patients developed cancer ( excluding nonmelanoma skin cancer ) . Incidence density rates for cancer diagnosis ( per 1,000 person-years ) were 33.7 for patients with HF and 15.6 for patients without HF ( p = 0.002 ) . The hazard ratio ( HR ) for cancer associated with HF was 2.16 ( 95 % confidence interval [ CI ] : 1.39 to 3.35 ) ; adjusted for age , sex , and Charlson comorbidity index ; HR : 1.71 ( 95 % CI : 1.07 to 2.73 ) . The HRs for mortality associated with cancer were 4.90 ( 95 % CI : 3.10 to 7.74 ) for HF-free and 3.91 ( 95 % CI : 1.88 to 8.12 ) for HF patients ( p for interaction = 0.76 ) . CONCLUSIONS Patients who develop HF after MI have an increased risk of cancer . This finding extends our previous report of an elevated cancer risk after HF compared with controls , and calls for a better underst and ing of shared risk factors and underlying mechanisms AIMS The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction ( HFPEF ) remain poorly characterized . This study aim ed to investigate this . METHODS AND RESULTS The Karolinska-Rennes ( KaRen ) Study was a multinational prospect i ve observational study design ed to characterize HFPEF . Inclusion required acute HF , defined by the Framingham criteria , LVEF ≥ 45 % , and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospect ively for 18 months . Predictors of the primary ( HF hospitalization or all-cause mortality ) and secondary ( all-cause mortality ) outcomes were assessed with multivariable Cox regression . A total of 539 patients [ 56 % women ; median ( interquartile range ) age 79 ( 72 - 84 ) years ; NT-pro-BNP/BNP 2448 (1290 - 4790)/429 ( 229 - 805 ) ng/L ] were included . Known history of HF was present in 40 % . Co-morbidities included hypertension ( 78 % ) , atrial fibrillation/flutter ( 65 % ) , anaemia ( 51 % ) , renal dysfunction ( 46 % ) , CAD ( 33 % ) , diabetes ( 30 % ) , lung disease ( 25 % ) , and cancer ( 16 % ) . The primary outcome occurred in 268 patients [ 50 % ; 106 deaths ( 20 % ) and 162 HF hospitalizations ( 30 % ) ] . Important independent predictors of the primary and /or secondary outcomes were age , history of non-cardiovascular syncope , valve disease , anaemia , lower sodium , and higher potassium , but no cardiovascular co-morbidities . Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis . CONCLUSION HFPEF was associated with higher age , female gender , hypertension , atrial fibrillation/flutter , and numerous non-cardiovascular co-morbidities . Prognosis was determined by non-cardiovascular co-morbidities , but use of conventional heart failure medications may still be associated with improved outcomes |
11,252 | 31,875,689 | Conclusions : Respiratory muscle training may be an effective alternative for improving respiratory muscle strength , swallowing function and phonatory parameters in subjects with Parkinson ’s disease . | Objective : To determine the effectiveness of respiratory muscle training in persons with Parkinson ’s disease . | Aim The aim of the present study was to compare threshold inspiratory muscle training ( IMT ) and expiratory muscle training ( EMT ) in elderly male patients with moderate degree of COPD . Material s and methods Forty male patients with moderate degree of COPD were recruited for this study . They were r and omly divided into two groups : the IMT group who received inspiratory training with an intensity ranging from 15 % to 60 % of their maximal inspiratory pressure , and the EMT group who received expiratory training with an equal intensity which was adjusted according to the maximal expiratory pressure . Both groups received training three times per week for 2 months , in addition to their prescribed medications . Results Both IMT and EMT groups showed a significant improvement in forced vital capacity , forced expiratory volume in the first second , forced expiratory volume in the first second% from the predicted values , and forced vital capacity% from the predicted value , with no difference between the groups . Both types of training result ed in a significant improvement in blood gases ( SaO2 % , PaO2 , PaCO2 , and HCO3 ) , with the inspiratory muscle group showing the best results . Both groups showed a significant improvement in the 6-min walking distance : an increase of about 25 % in the inspiratory muscle group and about 2.5 % in the expiratory muscle group . Conclusion Both IMT and EMT must be implemented in pulmonary rehabilitation programs in order to achieve improvements in pulmonary function test , respiratory muscle strength , blood oxygenation , and 6-min walking distance OBJECTIVE To determine the effects of a short- duration , combined ( inspiratory and expiratory ) , progressive resistance respiratory muscle training ( RMT ) protocol on respiratory muscle strength , fatigue , health-related quality of life , and functional performance in individuals with mild-to-moderate multiple sclerosis ( MS ) . DESIGN Quasi-experimental before-after trial . SETTING University rehabilitation research laboratory . PARTICIPANTS Volunteers with MS ( N=21 ) were divided into 2 groups : RMT ( n=11 ; 9 women , 2 men ; mean age ± SD , 50.9 ± 5.7y , mean Exp and ed Disability Status Scale score ± SD , 3.2 ± 1.9 ) and a control group that did not train ( n=10 ; 7 women , 3 men ; mean age ± SD , 56.2 ± 8.8y , mean Exp and ed Disability Status Scale score ± SD , 4.4 ± 2.1 ) . Exp and ed Disability Status Scale scores ranged from 1 to ≤6.5 . No patients withdrew from the study . INTERVENTION Training was a 5-week combined progressive resistance RMT program , 3d/wk , 30 minutes per session . MAIN OUTCOME MEASURES The primary outcome measures were maximal inspiratory pressure and expiratory pressure and the Modified Fatigue Impact Scale . All subjects completed secondary measures of pulmonary function , the six-minute walk test , the timed stair climb , the Multiple Sclerosis Self-Efficacy Scale , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the Physical Activity Disability Scale . RESULTS Maximal inspiratory pressure and expiratory pressure ( mean ± SD ) increased 35 % ± 22 % ( P<.001 ) and 26 % ± 17 % ( P<.001 ) , respectively , whereas no changes were noted in the control group ( 12 % ± 23 % and -4 % ± 17 % , respectively ) . RMT improved fatigue ( Modified Fatigue Impact Scale , P<.029 ) , with no change or worsening in the control group . No changes were noted in the six-minute walk test , stair climb , Multiple Sclerosis Self-Efficacy Scale , or Physical Activity Disability Scale in the RMT group . The control group had decreases in emotional well-being and general health ( Medical Outcomes Study 36-Item Short-Form Health Survey ) . CONCLUSIONS A short- duration , combined RMT program improved inspiratory and expiratory muscle strength and reduced fatigue in patients with mild to moderate MS Objective : Dysphagia is the main cause of aspiration pneumonia and death in Parkinson disease ( PD ) with no established restorative behavioral treatment to date . Reduced swallow safety may be related to decreased elevation and excursion of the hyolaryngeal complex . Increased submental muscle force generation has been associated with expiratory muscle strength training ( EMST ) and subsequent increases in hyolaryngeal complex movement provide a strong rationale for its use as a dysphagia treatment . The current study 's objective was to test the treatment outcome of a 4-week device-driven EMST program on swallow safety and define the physiologic mechanisms through measures of swallow timing and hyoid displacement . Methods : This was a r and omized , blinded , sham-controlled EMST trial performed at an academic center . Sixty participants with PD completed EMST , 4 weeks , 5 days per week , for 20 minutes per day , using a calibrated or sham , h and held device . Measures of swallow function including judgments of swallow safety ( penetration – aspiration [ PA ] scale scores ) , swallow timing , and hyoid movement were made from videofluoroscopic images . Results : No pretreatment group differences existed . The active treatment ( EMST ) group demonstrated improved swallow safety compared to the sham group as evidence d by improved PA scores . The EMST group demonstrated improvement of hyolaryngeal function during swallowing , findings not evident for the sham group . Conclusions : EMST may be a restorative treatment for dysphagia in those with PD . The mechanism may be explained by improved hyolaryngeal complex movement . Classification of evidence : This intervention study provides Class I evidence that swallow safety as defined by PA score improved post EMST BACKGROUND Pulmonary and respiratory muscle function impairment are common in patients with Parkinson 's disease ( PD ) . Inspiratory muscle training may improve strength , dyspnea and functional capacity in healthy subjects and in those with chronic obstructive pulmonary disease . This study investigated the effect of specific inspiratory muscle training ( SIMT ) on pulmonary functions , inspiratory muscle performance , dyspnea and quality of life , in patients with PD . PATIENTS AND METHODS Twenty patients with PD ( stage II and III Hoehn and Yahr scale ) were recruited for the study and were divided into two groups : ( a ) ten patients who received SIMT and ( b ) ten patients who received sham training , for three months . Pulmonary functions , the respiratory muscle strength and endurance , the perception of dyspnea ( POD ) and the quality of life were studied before and within one week after the training period . All subjects trained daily , six times a week , each session consisting of 1/2 hour , for 12 weeks . RESULTS Following the training period , there was a significant improvement , in the training group but not in the control group , in the following parameters : inspiratory muscle strength , ( PImax , increased from 62.0 + /- 8.2 to 78.0 + /- 7.5 cm of H2O ( p < 0.05 ) , inspiratory muscle endurance ( increased from 20.0 + /- 2.8 to 29.0 + /- 3.0 cm of H2O ( p < 0.05 ) , and the POD ( decreased from 17.9 + /- 3.2 to 14.0 + /- 2.4 units ( p < 0.05 ) . There was a close correlation between the increase in the inspiratory muscle performance and the decrease in the POD . CONCLUSIONS The inspiratory muscle performance may be improved by SIMT in patients with PD . This improvement is associated with a significant decrease in their POD BACKGROUND Recently , resistance expiratory muscle strength training ( EMST ) has been reported as a remedial treatment for dysphagia . OBJECTIVE To investigate the effect of resistance EMST on the swallowing function in stroke patients with oropharyngeal dysphagia . METHODS Forty-two stroke patients with dysphagia were r and omly assigned to two groups : an experimental group ( n = 13 ) and a placebo group ( n = 13 ) . The experimental group performed EMST using a portable EMST device , while the placebo group performed EMST using a sham EMST device with no loading . The intervention was performed 5 days per week for 4weeks , in five sets of 5 breaths through the device for a total of 25 breaths per day . Both groups underwent conventional dysphagia treatment for 30 minutes/day , 5 days/week , for 4 weeks . Videofluoroscopic dysphagia scale ( VDS ) and penetration-aspiration scale ( PAS ) based on a videofluoroscopic swallowing study ( VFSS ) were assessed to analyze the oropharyngeal swallowing function . RESULTS The experimental group showed more improvement in pharyngeal phase of the VDS ( p = 0.018 and 0.006 , respectively ) and PAS compared to the placebo group ( p = 0.014 ) . CONCLUSIONS We suggest that EMST could improve the effects of dysphagia observed in post-stroke elderly patients based on swallowing function Objective : To compare the effects of an inspiratory versus and expiratory muscle-training program on voluntary and reflex peak cough flow in patients with Parkinson disease . Design : A r and omized controlled study . Setting : Home-based training program . Participants : In all , 40 participants with diagnosis of Parkinson ’s disease were initially recruited in the study and r and omly allocated to three study groups . Of them , 31 participants completed the study protocol ( control group , n = 10 ; inspiratory training group , n = 11 ; and expiratory training group , n = 10 ) Intervention : The inspiratory and expiratory group performed a home-based inspiratory and expiratory muscle-training program , respectively ( five sets of five repetitions ) . Both groups trained six times a week for two months using a progressively increased resistance . The control group performed expiratory muscle training using the same protocol and a fixed resistance . Main measures : Spirometric indices , maximum inspiratory pressure , maximum expiratory pressure , and peak cough flow during voluntary and reflex cough were assessed before and at two months after training . Results : The magnitude of increase in maximum expiratory pressure ( d = 1.40 ) and voluntary peak cough flow ( d = 0.89 ) was greater for the expiratory muscle-training group in comparison to the control group . Reflex peak cough flow had a moderate effect ( d = 0.27 ) in the expiratory group in comparison to the control group . Slow vital capacity ( d = 0.13 ) and forced vital capacity ( d = 0.02 ) had trivial effects in the expiratory versus the control group . Conclusions : Two months of expiratory muscle-training program was more beneficial than inspiratory muscle-training program for improving maximum expiratory pressure and voluntary peak cough flow in patients with Parkinson ’s disease Expiratory muscle strength training ( EMST ) involves forcible blowing as a means of generating high expiratory pressure , against adjustable resistance . EMST has recently been introduced as a potential treatment for dysphagia . This study was performed to investigate the effects of EMST on the activity of suprahyoid muscles , aspiration and dietary stages in stroke patients with dysphagia . Twenty-seven stroke patients with dysphagia were r and omly divided into two groups . The experimental group performed EMST with a 70 % threshold value of maximal expiratory pressure , using an EMST device , 5 days a week for 4 weeks . The placebo group trained with a sham device . The EMST regime involved 5 sets of 5 breaths through the EMST device for a total of 25 breaths per day . Activity in the suprahyoid muscle group was measured using surface electromyography ( sEMG ) . Further , the penetration-aspiration scale ( PAS ) was used to assess the results of the videofluoroscopic swallowing study ( VFSS ) . In addition , dietary stages were evaluated using the Functional Oral Intake Scale ( FOIS ) . The experimental group exhibited improved suprahyoid muscle group activity and PAS results , when compared to the placebo group . Following intervention , statistical analysis indicated significant differences in measured suprahyoid muscle activity ( P = 0·01 ) , liquid PAS outcomes ( P = 0·03 ) and FOIS results ( P = 0·06 ) , but not semisolid type PAS outcomes ( P = 0·32 ) , between the groups . This study confirms EMST as an effective treatment for the development of suprahyoid muscle activity in stroke patients with dysphagia . Additionally , improvements in aspiration and penetration outcomes were observed 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 . Respiratory symptoms are recognized as sequelae of motor dysfunction in idiopathic Parkinson 's disease ( IPD ) and these symptoms have the potential to cause problems with swallow , cough , voice and speech . Specifically , maneuvers that require rapid activation and coordination of upper airway and chest wall musculature become progressively impaired as motor dysfunction progresses during the natural course of the disease . This study reports on the maximum inspiratory and expiratory pressures produced by 28 participants ( average age 64 ) diagnosed with moderate to severe IPD ( average stage 2.5 with a range of 2.0 - 3.0 ) . All measures were collected during the " medication on " state . Outcomes of a specific respiratory muscle strength training technique for improving maximum expiratory pressure are reported for three of the patients in this study . Techniques that focus on strengthening the respiratory muscles in patients with IPD ( other than with low load breathing exercises ) , have not been previously reported . The results of this pilot study demonstrate that respiratory muscle weakness may be an important factor in the respiratory complications in IPD and that respiratory muscle strength training has the potential to improve expiratory muscle strength for this population . This improvement has the potential to positively impact high forced respiratory activities , such as forced breathing maneuvers , swallow , cough and speech functions that require greater magnitude and duration of expiration 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 evaluate the contribution of respiratory muscle weakness ( part 1 ) and respiratory muscle training ( part 2 ) to pulmonary function , cough efficacy , and functional status in patients with advanced multiple sclerosis ( MS ) . DESIGN Survey ( part 1 ) and r and omized controlled trial ( part 2 ) . SETTING Rehabilitation center for MS . PATIENTS Twenty-eight bedridden or wheelchair-bound MS patients ( part 1 ) ; 18 patients were r and omly assigned to a training group ( n = 9 ) or a control group ( n = 9 ) ( part 2 ) . INTERVENTION The training group ( part 2 ) performed three series of 15 contractions against an expiratory resistance ( 60 % maximum expiratory pressure [ PEmax ] ) two times a day , whereas the control group performed breathing exercises to enhance maximal inspirations . MAIN OUTCOME MEASURES Forced vital capacity ( FVC ) , inspiratory , and expiratory muscle strength ( PImax and PEmax ) , neck flexion force ( NFF ) , cough efficacy by means of the Pulmonary Index ( PI ) , and functional status by means of the Extended Disability Status Scale ( EDSS ) . RESULTS Part 1 revealed a significantly reduced FVC ( 43 % + /- 26 % predicted ) , PEmax ( 18 % + /- 8 % predicted ) , and PImax ( 27 % + /- 11 % predicted ) , whereas NFF was only mildly reduced ( 93 % + /- 26 % predicted ) . The PI ( median score , 10 ) and EDSS ( median score , 8.5 ) were severely reduced . PEmax was significantly correlated to FVC , EDSS , and PI ( r = .77 , -.79 , and -.47 , respectively ) . In stepwise multiple regression analysis . PEmax was the only factor contributing to the explained variance in FVC ( R2 = .60 ) , whereas body weight ( R2 = .41 ) was the only factor for the PI . In part 2 , changes in PImax and PEmax tended to be higher in the training group ( p = .06 and p = .07 , respectively ) . The PI was significantly improved after 3 months of training compared with the control group ( p < .05 ) . After 6 months , the PI remained significantly better in the training group . CONCLUSIONS Expiratory muscle strength was significantly reduced and related to FVC , cough efficacy , and functional status . Expiratory muscle training tended to enhance inspiratory and expiratory muscle strength . In addition , subjectively and objective ly rated cough efficacy improved significantly and lasted for 3 months after training cessation INTRODUCTION In individuals with Parkinson 's disease ( PD ) , respiratory muscle weakness and rigidity , bradykinesia of abdominal muscles and stiffness of the chest wall , affect the respiratory component of voice intensity due to reduced pulmonary capacity and airflow needed to vibrate the vocal folds . It may be possible to improve voice production by strengthening respiratory muscles . The purpose of this study was to evaluate the effects of inspiratory and expiratory muscle training on voice production outcomes in individuals with PD . METHOD Thirty-one participants with PD were r and omly allocated to three study groups ( control group n = 10 , inspiratory training group , n = 11 , and expiratory training group , n = 11 ) . The inspiratory and expiratory group performed a home-based inspiratory and expiratory muscle training program , respectively ( five sets of five repetitions ) . Both groups trained six times a week for 2 months using a progressively increased resistance . The control group performed expiratory muscle training using the same protocol and a fixed resistance . Phonatory measures , maximum inspiratory/expiratory pressure , and spirometric indexes were assessed before and at 2 months after training . RESULTS Differences in peak subglottic pressure were moderate ( d = 0.59 ) between expiratory and inspiratory groups , large between inspiratory and control groups ( d = 1.32 ) , and large between expiratory and control groups ( d = 1.96 ) . Differences in maximum phonation time were large ( d = 1.26 ) between inspiratory and control groups , moderate ( negative ) between expiratory and inspiratory groups ( d = -0.60 ) , and moderate between expiratory and control groups ( d = 0.72 ) . Differences in peak sound pressure level were large ( d = 1.27 ) between inspiratory and control groups , trivial between expiratory and inspiratory groups ( d = -0.18 ) , and large between expiratory and control groups ( d = 1.10 ) . CONCLUSIONS Inspiratory muscle training is effective in improving maximum phonation time , and expiratory muscle training is more effective for improving peak subglottic pressure , and peak sound pressure level in individuals with PD BACKGROUND Aspiration pneumonia is a leading cause of death in people with Parkinson disease ( PD ) . The pathogenesis of these infections is largely attributed to the presence of dysphagia with silent aspiration or aspiration without an appropriate cough response . The goal of this study was to test reflex cough thresholds and associated urge-to-cough ( UTC ) ratings in participants with PD with and without dysphagia . METHODS Twenty participants with PD were recruited for this study . They completed a capsaicin challenge with three r and omized blocks of 0 , 50 , 100 , and 200 μM capsaicin and rated their UTC by modified Borg scale . The concentration of capsaicin that elicited a two-cough response , total number of coughs , and sensitivity of the participant to the cough stimulus ( UTC ) were measured . The dysphagia severity of participants with PD was identified with the penetration-aspiration scale . RESULTS Most participants with PD did not have a consistent two-cough response to 200 μM capsaicin . UTC ratings and total number of coughs produced at 200 μM capsaicin were significantly influenced by dysphagia severity but not by general PD severity , age , or disease duration . Increasing levels of dysphagia severity result ed in significantly blunted cough sensitivity ( UTC ) . CONCLUSIONS UTC ratings may be important in underst and ing the mechanism underlying morbidity related to aspiration pneumonia in people with PD and dysphagia . Further underst and ing of decreased UTC in people with PD and dysphagia will be essential for the development of strategies and treatments to address airway protection deficits in this population |
11,253 | 22,301,923 | Chocolate or cocoa improved FMD regardless of the dose consumed , whereas doses > 50 mg epicatechin/d result ed in greater effects on systolic and diastolic BP .
GRADE ( Grading of Recommendations , Assessment , Development and Evaluation , a tool to assess quality of evidence and strength of recommendations ) suggested low- to moderate- quality evidence of beneficial effects , with no suggestion of negative effects .
We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR . | BACKGROUND There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease ( CVD ) .
OBJECTIVE The objective was to systematic ally review the effects of chocolate , cocoa , and flavan-3-ols on major CVD risk factors . | Evidence suggests that flavonoid-containing diets reduce cardiovascular risk , but the mechanisms responsible are unclear . In the present study , we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD ( coronary artery disease ) . Forty subjects ( 61+/-8 years ; 30 male ) with CAD were recruited to a 6-week r and omized double-blind placebo-controlled study . Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily ( total flavanols , 444 mg/day ) or matching isocaloric placebos daily ( total flavanols , 19.6 mg/day ) for 6 weeks . Brachial artery FMD ( flow-mediated dilation ) and SAC ( systemic arterial compliance ) were assessed at baseline , 90 min following the first beverage and after 3 and 6 weeks of daily consumption . Soluble cellular adhesion molecules and FBF ( forearm blood flow ) responses to ACh ( acetylcholine chloride ; 3 - 30 microg/min ) and SNP ( sodium nitroprusside ; 0.3 - 3 microg/min ) infusions , forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks . FMD , SAC and FBF responses did not differ between groups at baseline . No acute or chronic changes in FMD or SAC were seen in either group . No difference in soluble cellular adhesion molecules , FBF responses to ischaemia , exercise , SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks . These data suggest that over a 6-week period , flavanol-rich cocoa does not modify vascular function in patients with established CAD Background Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease ( CVD ) due to chocolate 's high levels of stearic acid and antioxidant flavonoids . However , debate still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall . Methods We review ed English- language MEDLINE publications from 1966 through January 2005 for experimental , observational , and clinical studies of relations between cocoa , cacao , chocolate , stearic acid , flavonoids ( including flavonols , flavanols , catechins , epicatechins , and procynadins ) and the risk of cardiovascular disease ( coronary heart disease ( CHD ) , stroke ) . A total of 136 publications were selected based on relevance , and quality of design and methods . An up date d meta- analysis of flavonoid intake and CHD mortality was also conducted . Results The body of short-term r and omized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure , anti-inflammation , anti-platelet function , higher HDL , decreased LDL oxidation . Additionally , a large body of trials of stearic acid suggests it is indeed cholesterol-neutral . However , epidemiologic studies of serum and dietary stearic acid are inconclusive due to many method ologic limitations . Meanwhile , the large body of prospect i ve studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality . Our up date d meta- analysis indicates that intake of flavonoids may lower risk of CHD mortality , RR = 0.81 ( 95 % CI : 0.71–0.92 ) comparing highest and lowest tertiles . Conclusion Multiple lines of evidence from laboratory experiments and r and omized trials suggest stearic acid may be neutral , while flavonoids are likely protective against CHD mortality . The highest priority now is to conduct larger r and omized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes Consumption of flavanol-rich dark chocolate ( DC ) has been shown to decrease blood pressure ( BP ) and insulin resistance in healthy subjects , suggesting similar benefits in patients with essential hypertension ( EH ) . Therefore , we tested the effect of DC on 24-hour ambulatory BP , flow-mediated dilation ( FMD ) , and oral glucose tolerance tests ( OGTTs ) in patients with EH . After a 7-day chocolate-free run-in phase , 20 never-treated , grade I patients with EH ( 10 males ; 43.7±7.8 years ) were r and omized to receive either 100 g per day DC ( containing 88 mg flavanols ) or 90 g per day flavanol-free white chocolate ( WC ) in an isocaloric manner for 15 days . After a second 7-day chocolate-free period , patients were crossed over to the other treatment . Noninvasive 24-hour ambulatory BP , FMD , OGTT , serum cholesterol , and markers of vascular inflammation were evaluated at the end of each treatment . The homeostasis model assessment of insulin resistance ( HOMA-IR ) , quantitative insulin sensitivity check index ( QUICKI ) , and insulin sensitivity index ( ISI ) were calculated from OGTT values . Ambulatory BP decreased after DC ( 24-hour systolic BP −11.9±7.7 mm Hg , P<0.0001 ; 24-hour diastolic BP −8.5±5.0 mm Hg , P<0.0001 ) but not WC . DC but not WC decreased HOMA-IR ( P<0.0001 ) , but it improved QUICKI , ISI , and FMD . DC also decreased serum LDL cholesterol ( from 3.4±0.5 to 3.0±0.6 mmol/L ; P<0.05 ) . In summary , DC decreased BP and serum LDL cholesterol , improved FMD , and ameliorated insulin sensitivity in hypertensives . These results suggest that , while balancing total calorie intake , flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH BACKGROUND Studies suggest cardioprotective benefits of dark chocolate containing cocoa . OBJECTIVE This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults . DESIGN R and omized , placebo-controlled , single-blind crossover trial of 45 healthy adults [ mean age : 53 y ; mean body mass index ( in kg/m(2 ) ) : 30 ] . In phase 1 , subjects were r and omly assigned to consume a solid dark chocolate bar ( containing 22 g cocoa powder ) or a cocoa-free placebo bar ( containing 0 g cocoa powder ) . In phase 2 , subjects were r and omly assigned to consume sugar-free cocoa ( containing 22 g cocoa powder ) , sugared cocoa ( containing 22 g cocoa powder ) , or a placebo ( containing 0 g cocoa powder ) . RESULTS Solid dark chocolate and liquid cocoa ingestion improved endothelial function ( measured as flow-mediated dilatation ) compared with placebo ( dark chocolate : 4.3 + /- 3.4 % compared with -1.8 + /- 3.3 % ; P < 0.001 ; sugar-free and sugared cocoa : 5.7 + /- 2.6 % and 2.0 + /- 1.8 % compared with -1.5 + /- 2.8 % ; P < 0.001 ) . Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo ( dark chocolate : systolic , -3.2 + /- 5.8 mm Hg compared with 2.7 + /- 6.6 mm Hg ; P < 0.001 ; and diastolic , -1.4 + /- 3.9 mm Hg compared with 2.7 + /- 6.4 mm Hg ; P = 0.01 ; sugar-free cocoa : systolic , -2.1 + /- 7.0 mm Hg compared with 3.2 + /- 5.6 mm Hg ; P < 0.001 ; and diastolic : -1.2 + /- 8.7 mm Hg compared with 2.8 + /- 5.6 mm Hg ; P = 0.014 ) . Endothelial function improved significantly more with sugar-free than with regular cocoa ( 5.7 + /- 2.6 % compared with 2.0 + /- 1.8 % ; P < 0.001 ) . CONCLUSIONS The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults . Sugar content may attenuate these effects , and sugar-free preparations may augment them BACKGROUND Numerous studies indicate that flavanols may exert significant vascular protection because of their antioxidant properties and increased nitric oxide bioavailability . In turn , nitric oxide bioavailability deeply influences insulin-stimulated glucose uptake and vascular tone . Thus , flavanols may also exert positive metabolic and pressor effects . OBJECTIVE The objective was to compare the effects of either dark or white chocolate bars on blood pressure and glucose and insulin responses to an oral-glucose-tolerance test in healthy subjects . DESIGN After a 7-d cocoa-free run-in phase , 15 healthy subjects were r and omly assigned to receive for 15 d either 100 g dark chocolate bars , which contained approximately 500 mg polyphenols , or 90 g white chocolate bars , which presumably contained no polyphenols . Successively , subjects entered a further cocoa-free washout phase of 7 d and then were crossed over to the other condition . Oral-glucose-tolerance tests were performed at the end of each period to calculate the homeostasis model assessment of insulin resistance ( HOMA-IR ) and the quantitative insulin sensitivity check index ( QUICKI ) ; blood pressure was measured daily . RESULTS HOMA-IR was significantly lower after dark than after white chocolate ingestion ( 0.94 + /- 0.42 compared with 1.72 + /- 0.62 ; P < 0.001 ) , and QUICKI was significantly higher after dark than after white chocolate ingestion ( 0.398 + /- 0.039 compared with 0356 + /- 0.023 ; P = 0.001 ) . Although within normal values , systolic blood pressure was lower after dark than after white chocolate ingestion ( 107.5 + /- 8.6 compared with 113.9 + /- 8.4 mm Hg ; P < 0.05 ) . CONCLUSION Dark , but not white , chocolate decreases blood pressure and improves insulin sensitivity in healthy persons Cocoa powder is rich in polyphenols , such as catechins and procyanidins , and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis . Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder ( 13 , 19.5 , and 26 g/d ) in normocholesterolemic and mildly hypercholesterolemic humans . In this comparative , double-blind study , we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds ( placebo-cocoa group ) or 3 levels of cocoa powder containing high-polyphenolic compounds ( 13 , 19.5 , and 26 g/d for low- , middle- , and high-cocoa groups , respectively ) for 4 wk . The test powders were consumed as a beverage after the addition of hot water , twice each day . Blood sample s were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids . Plasma oxidized LDL concentrations decreased in the low- , middle- , and high-cocoa groups compared with baseline . A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or = 3.23 mmol/L at baseline . In these subjects , plasma LDL cholesterol , oxidized LDL , and apo B concentrations decreased , and the plasma HDL cholesterol concentration increased , relative to baseline in the low- , middle- , and high-cocoa groups . The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol , an elevation in HDL cholesterol , and the suppression of oxidized LDL Flavanols from chocolate appear to increase nitric oxide bioavailability , protect vascular endothelium , and decrease cardiovascular disease ( CVD ) risk factors . We sought to test the effect of flavanol-rich dark chocolate ( FRDC ) on endothelial function , insulin sensitivity , beta-cell function , and blood pressure ( BP ) in hypertensive patients with impaired glucose tolerance ( IGT ) . After a run-in phase , 19 hypertensives with IGT ( 11 males , 8 females ; 44.8 + /- 8.0 y ) were r and omized to receive isocalorically either FRDC or flavanol-free white chocolate ( FFWC ) at 100 g/d for 15 d. After a wash-out period , patients were switched to the other treatment . Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry , respectively , flow-mediated dilation ( FMD ) , oral glucose tolerance test , serum cholesterol and C-reactive protein , and plasma homocysteine were evaluated after each treatment phase . FRDC but not FFWC ingestion decreased insulin resistance ( homeostasis model assessment of insulin resistance ; P < 0.0001 ) and increased insulin sensitivity ( quantitative insulin sensitivity check index , insulin sensitivity index ( ISI ) , ISI(0 ) ; P < 0.05 ) and beta-cell function ( corrected insulin response CIR(120 ) ; P = 0.035 ) . Systolic ( S ) and diastolic ( D ) BP decreased ( P < 0.0001 ) after FRDC ( SBP , -3.82 + /- 2.40 mm Hg ; DBP , -3.92 + /- 1.98 mm Hg ; 24-h SBP , -4.52 + /- 3.94 mm Hg ; 24-h DBP , -4.17 + /- 3.29 mm Hg ) but not after FFWC . Further , FRDC increased FMD ( P < 0.0001 ) and decreased total cholesterol ( -6.5 % ; P < 0.0001 ) , and LDL cholesterol ( -7.5 % ; P < 0.0001 ) . Changes in insulin sensitivity ( Delta ISI - Delta FMD : r = 0.510 , P = 0.001 ; Delta QUICKI - Delta FMD : r = 0.502 , P = 0.001 ) and beta-cell function ( Delta CIR(120 ) - Delta FMD : r = 0.400 , P = 0.012 ) were directly correlated with increases in FMD and inversely correlated with decreases in BP ( Delta ISI - Delta 24-h SBP : r = -0.368 , P = 0.022 ; Delta ISI - Delta 24-h DBP r = -0.384 , P = 0.017 ) . Thus , FRDC ameliorated insulin sensitivity and beta-cell function , decreased BP , and increased FMD in IGT hypertensive patients . These findings suggest flavanol-rich , low-energy cocoa food products may have a positive impact on CVD risk factors BACKGROUND Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis . OBJECTIVE We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects . DESIGN Twenty-five subjects were r and omly assigned to ingest either 12 g sugar/d ( control group ) or 26 g cocoa powder and 12 g sugar/d ( cocoa group ) for 12 wk . Blood sample s were collected before the study and 12 wk after intake of the test drinks . Plasma lipids , LDL oxidative susceptibility , and urinary oxidative stress markers were measured . RESULTS At 12 wk , we measured a 9 % prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group . This prolongation in the cocoa group was significantly greater than the reduction measured in the control group ( -13 % ) . A significantly greater increase in plasma HDL cholesterol ( 24 % ) was observed in the cocoa group than in the control group ( 5 % ) . A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL . At 12 wk , there was a 24 % reduction in dityrosine from baseline concentrations in the cocoa group . This reduction in the cocoa group was significantly greater than the reduction in the control group ( -1 % ) . CONCLUSION It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol BACKGROUND In recent years , there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa . OBJECTIVE The objective of the study was to examine the short-term ( 6 wk ) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults . DESIGN A double-blind , placebo-controlled , fixed-dose , parallel-group clinical trial was used . Participants ( n = 101 ) were r and omly assigned to receive a 37-g dark chocolate bar and 8 ounces ( 237 mL ) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk . RESULTS No significant group ( dark chocolate and cocoa or placebo)-by-trial ( baseline , midpoint , and end-of-treatment assessment s ) interactions were found for the neuropsychological , hematological , or blood pressure variables examined . In contrast , the midpoint and end-of-treatment mean pulse rate assessment s in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group . Results of a follow-up question naire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment . CONCLUSIONS This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research . Consumption of dark chocolate and cocoa was , however , associated with significantly higher pulse rates at 3- and 6-wk treatment assessment BACKGROUND Flavonoids are polyphenolic compounds of plant origin with antioxidant effects . Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro . Little is known about how cocoa powder and dark chocolate , rich sources of polyphenols , affect these cardiovascular disease risk factors . OBJECTIVE We evaluated the effects of a diet high in cocoa powder and dark chocolate ( CP-DC diet ) on LDL oxidative susceptibility , serum total antioxidant capacity , and urinary prostagl and in concentrations . DESIGN We conducted a r and omized , 2-period , crossover study in 23 healthy subjects fed 2 diets : an average American diet ( AAD ) controlled for fiber , caffeine , and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate ( CP-DC diet ) , providing approximately 466 mg procyanidins/d . RESULTS LDL oxidation lag time was approximately 8 % greater ( P = 0.01 ) after the CP-DC diet than after the AAD . Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4 % greater ( P = 0.04 ) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time ( r = 0.32 , P = 0.03 ) . HDL cholesterol was 4 % greater after the CP-DC diet ( P = 0.02 ) than after the AAD ; however , LDL-HDL ratios were not significantly different . Twenty-four-hour urinary excretion of thromboxane B(2 ) and 6-keto-prostagl and in F(1)(alpha ) and the ratio of the 2 compounds were not significantly different between the 2 diets . CONCLUSION Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility , increasing serum total antioxidant capacity and HDL-cholesterol concentrations , and not adversely affecting prostagl and ins BACKGROUND Flavonoids may be partly responsible for some health benefits , including antiinflammatory action and a decreased tendency for the blood to clot . An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans . OBJECTIVE This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo . DESIGN Thirty-two healthy subjects were assigned to consume active ( 234 mg cocoa flavanols and procyanidins/d ) or placebo ( < or = 6 mg cocoa flavanols and procyanidins/d ) tablets in a blinded parallel- design ed study . Platelet function was determined by measuring platelet aggregation , ATP release , and expression of activation-dependent platelet antigens by using flow cytometry . Plasma was analyzed for oxidation markers and antioxidant status . RESULTS Plasma concentrations of epicatechin and catechin in the active group increased by 81 % and 28 % , respectively , during the intervention period . The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group . Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group ( P < 0.05 ) , whereas plasma oxidation markers and antioxidant status did not change in either group . CONCLUSIONS Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function . These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins BACKGROUND Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease . Because atherosclerosis is considered a low- grade inflammatory disease , some feeding trials have analyzed the effects of cocoa ( an important source of flavonoids ) on inflammatory biomarkers , but the results have been controversial . OBJECTIVE The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients . DESIGN Forty-two high-risk volunteers ( 19 men and 23 women ; mean + /- SD age : 69.7 + /- 11.5 y ) were included in a r and omized crossover feeding trial . All subjects received 40 g cocoa powder with 500 mL skim milk/d ( C+M ) or only 500 mL skim milk/d ( M ) for 4 wk . Before and after each intervention period , cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated . RESULTS Adherence to the dietary protocol was excellent . No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups . However , in monocytes , the expression of VLA-4 , CD40 , and CD36 was significantly lower ( P = 0.005 , 0.028 , and 0.001 , respectively ) after C+M intake than after M intake . In addition , serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower ( both P = 0.007 ) after C+M intake than after M intake . CONCLUSIONS These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease . These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis . This trial was registered in the Current Controlled Trials at London , International St and ard R and omized Controlled Trial Number , at controlled-trials.com as IS RCT N75176807 BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Background : Dark chocolate derived from the plant ( Theobroma cacao ) is a rich source of flavonoids . Cardioprotective effects including antioxidant properties , inhibition of platelet activity , and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids . Objective : To investigate the effects of flavonoid-rich dark chocolate on endothelial function , measures of oxidative stress , blood lipids , and blood pressure in healthy adult subjects . Design : The study was a r and omized , double-blind , placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects . Subjects were r and omly assigned to daily intake of high-flavonoid ( 213 mg procyanidins , 46 mg epicatechin ) or low-flavonoid dark chocolate bars ( 46 g , 1.6 oz ) . Results : High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation ( FMD ) of the brachial artery ( mean change = 1.3 ± 0.7 % ) as compared to low-flavonoid chocolate consumption ( mean change = −0.96 ± 0.5 % ) ( p = 0.024 ) . No significant differences were noted in the resistance to LDL oxidation , total antioxidant capacity , 8-isoprostanes , blood pressure , lipid parameters , body weight or body mass index ( BMI ) between the two groups . Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group ( 204.4 ± 18.5 nmol/L , p ≤ 0.001 ) but not in the low-flavonoid group ( 17.5 ± 9 nmol/L , p = 0.99 ) . Conclusion : Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults . No changes in oxidative stress measures , lipid profiles , blood pressure , body weight or BMI were seen Background Flavanol-rich chocolate and lycopene-rich tomato extract have attracted interest as potential alternative treatment options for hypertension , a known risk factor for cardiovascular morbidity and mortality . Treatment of prehypertension ( SBP 120–139/DBP 80–89 mmHg ) may forestall progression to hypertension . However , there has been only limited research into non-pharmacological treatment options for prehypertension . We investigated the effect of dark chocolate or tomato extract on blood pressure , and their acceptability as an ongoing treatment option in a prehypertensive population . Methods Our trial consisted of two phases : a r and omised controlled three-group-parallel trial over 12 weeks ( phase 1 ) followed by a crossover of the two active treatment arms over an additional 12-week period ( phase 2 ) . Group 1 received a 50 g daily dose of dark chocolate with 70 % cocoa containing 750 mg polyphenols , group 2 were allocated one tomato extract capsule containing 15 mg lycopene per day , and group 3 received one placebo capsule daily over 8 weeks followed by a 4-week washout period . In phase 2 the active treatment groups were crossed over to receive the alternative treatment . Median blood pressure , weight , and abdominal circumference were measured 4-weekly , and other characteristics including physical activity , general health , energy , mood , and acceptability of treatment were assessed by question naire at 0 , 8 and 20 weeks . We analysed changes over time using a linear mixed model , and one time point differences using Kruskal-Wallis , Fisher's-Exact , or t-tests . Results Thirty-six prehypertensive healthy adult volunteers completed the 6-month trial . Blood pressure changes over time within groups and between groups were not significant and independent of treatment . Weight and other characteristics did not change significantly during the trial . However , a marked difference in acceptability between the two treatment forms ( chocolate or capsule ) was revealed ( p < 0.0001 ) . Half of the participants allocated to the chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20 % considered it an unacceptable long-term treatment option , whereas all participants found it easy and acceptable to take a capsule each day for blood pressure . Conclusion Our study did not find a blood pressure lowering effect of dark chocolate or tomato extract in a prehypertensive population . Practicability of chocolate as a long-term treatment option may be limited . Trial registration http://www.anzctr.org.au Identifier : Background Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer . The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome ( CFS ) has not been studied previously . Methods We conducted a double blinded , r and omised , clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate ( HCL/PR ) in comparison to simulated iso-calorific chocolate ( cocoa liquor free/low polyphenols(CLF/LP ) ) on fatigue and residual function in subjects with chronic fatigue syndrome . Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled . Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP , with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate . Results Ten subjects were enrolled in the study . The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [ median ( range ) Exact Sig . ( 2-tailed ) ] [ 33 ( 25 - 38 ) vs. 21.5 ( 6 - 35 ) 0.01 ] , but that deteriorated significantly when subjects were given simulated iso-calorific chocolate ( CLF/CP ) [ 28.5 ( 17 - 20 ) vs. 34.5 ( 13 - 26 ) 0.03 ] . The residual function , as assessed by the London H and icap scale , also improved significantly after the HCL/PR arm [ 0.49 ( 0.33 - 0.62 ) vs. 0.64 ( 0.44 - 0.83 ) 0.01 ] and deteriorated after iso-calorific chocolate [ 00.44 ( 0.43 - 0.68 ) vs. 0.36 ( 0.33 - 0.62)0.03 ] . Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm , but deteriorated after CLF/CP . Mean weight remained unchanged throughout the trial . Conclusion This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome The consumption of a diet rich in certain flavonoids , including the flavanol sub-class , has been associated with a reduced risk for vascular disease . We evaluated the effects of the regular consumption ( 14 d ) of a flavanol-containing milk chocolate ( FCMC ) or cocoa butter chocolate ( CBC ) on variables related to vascular disease risk , oxidative stress and physical activity . Twenty-eight free-living , young ( 18–20 years old ) male soccer players consumed daily 105 g of FCMC ( 168 mg of flavanols ) or CBC ( < 5 mg of flavanols ) , as part of their normal diet . The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure ( -5 mm Hg ) , mean blood pressure ( -5 mm Hg ) , plasma cholesterol ( -11 % ) , LDL-cholesterol ( -15 % ) , malondialdehyde ( -12 % ) , urate ( -11 % ) and lactate dehydrogenase ( LDH ) activity ( -11 % ) , and an increase in vitamin E/cholesterol ( + 12 % ) . No relevant changes in these variables were associated with CBC consumption . No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood sample s. In conclusion , FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress . The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results OBJECTIVES To assess the long-term effects of chocolate consumption amongst patients with established coronary heart disease . DESIGN In a population -based inception cohort study , we followed 1169 non-diabetic patients hospitalized with a confirmed first acute myocardial infa rct ion ( AMI ) between 1992 and 1994 in Stockholm County , Sweden , as part of the Stockholm Heart Epidemiology Program . Participants self-reported usual chocolate consumption over the preceding 12 months with a st and ardized question naire distributed during hospitalization and underwent a health examination 3 months after discharge . Participants were followed for hospitalizations and mortality with national registries for 8 years . RESULTS Chocolate consumption had a strong inverse association with cardiac mortality . When compared with those never eating chocolate , the multivariable-adjusted hazard ratios were 0.73 ( 95 % confidence interval , 0.41 - 1.31 ) , 0.56 ( 0.32 - 0.99 ) and 0.34 ( 0.17 - 0.70 ) for those consuming chocolate less than once per month , up to once per week and twice or more per week respectively . Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes . In contrast , intake of other sweets was not associated with cardiac or total mortality . CONCLUSIONS Chocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI . Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds , confirmation of this strong inverse relationship from other observational studies or large-scale , long-term , controlled r and omized trials is needed Impaired endothelial vasodilatation may contribute to the exaggerated blood pressure ( BP ) responses to exercise in individuals who are overweight/obese . The present study investigated whether consumption of cocoa flavanols , which improve endothelium-dependent flow-mediated dilatation ( FMD ) , can modify BP responsiveness to exercise . Twenty-one volunteers ( eight females and thirteen males , 54.9 ( se 2.2 ) years , BMI 31.6 ( se 0.8 ) kg/m2 , systolic BP 134 ( se 2 ) mmHg , diastolic BP ( DBP ) 87 ( se 2 ) mmHg ) were r and omised to consume single servings of either a high-flavanol ( HF , 701 mg ) or a low-flavanol ( LF , 22 mg ) cocoa beverage in a double-blind , cross-over design with 3 - 7-d washout between treatments . Two hours after cocoa consumption , FMD was measured , followed by continuous beat-to-beat assessment ( Finapres ) of BP before and during 10 min of cycling at 75 % of age-predicted maximum heart rate . Averaged data from two assessment s on each type of beverage were compared by analysis of covariance using pre-exercise BP as the covariate . Pre-exercise BP was similar after taking LF and HF ( 153 ( se 3)/88 ( se 3 ) v. 153 ( se 4)/87 ( se 2 ) mmHg , respectively , P>0.05 ) . However , the BP response to exercise ( area under BP curve ) was attenuated by HF compared with LF . BP increases were 68 % lower for DBP ( P = 0.03 ) and 14 % lower for mean BP ( P = 0.05 ) . FMD measurements were higher after taking HF than after taking LF ( 6.1 ( se 0.6 ) % v. 3.4 ( se 0.5 ) % , P < 0.001 ) . By facilitating vasodilation and attenuating exercise-induced increases in BP , cocoa flavanols may decrease cardiovascular risk and enhance the cardiovascular benefits of moderate intensity exercise in at-risk individuals OBJECTIVE The prospect i ve association between insulin levels and risk of cardiovascular disease ( CVD ) is controversial . The objective of the present study was to investigate the relationship of the homeostasis model assessment of insulin resistance ( HOMA-IR ) , as well as insulin levels , with risk of nonfatal and fatal CVD over the 8-year follow-up of the San Antonio Heart Study . RESEARCH DESIGN AND METHODS Between 1984 and 1988 , r and omly selected Mexican-American and non-Hispanic white residents of San Antonio participated in baseline examinations that included fasting blood sample s for glucose , insulin , and lipids , a glucose tolerance test , anthropometric measurements , and a lifestyle question naire . Between 1991 and 1996 , 2,569 subjects who were free of diabetes at baseline were reexamined using the same protocol . RESULTS Over the follow-up period , 187 subjects experienced an incident cardiovascular event ( heart attack , stroke , heart surgery , angina , or CVD death ) . Logistic regression analysis indicated that risk of a CVD event increased across quintiles of HOMA-IR after adjustment for age , sex , and ethnicity ( P for trend < 0.0001 ; quintile 5 vs. quintile 1 , odds ratio [ OR ] 2.52 , 95 % CI 1.46 - 4.36 ) . Additional adjustment for LDL , triglyceride , HDL , systolic blood pressure , smoking , alcohol consumption , exercise , and waist circumference only modestly reduced the magnitude of these associations ( P for trend 0.02 ; quintile 5 vs. quintile 1 , OR 1.94 , 95 % CI 1.05 - 3.59 ) . Furthermore , there were no significant interactions between HOMA-IR and ethnicity , sex , hypertension , dyslipidemia , glucose tolerance ( impaired glucose tolerance versus normal glucose tolerance ) , or obesity . The magnitude and direction of the relationship between insulin concentration and incident CVD were similar . CONCLUSIONS We found a significant association between HOMA-IR and risk of CVD after adjustment for multiple covariates . The topic remains controversial , however , and additional studies are required , particularly among women and minority population BACKGROUND Small , short-term , intervention studies indicate that cocoa-containing foods improve endothelial function and reduce blood pressure . We studied whether habitual cocoa intake was cross-sectionally related to blood pressure and prospect ively related with cardiovascular mortality . METHODS Data used were of 470 elderly men participating in the Zutphen Elderly Study and free of chronic diseases at baseline . Blood pressure was measured at baseline and 5 years later , and causes of death were ascertained during 15 years of follow-up . Habitual food consumption was assessed by the cross-check dietary history method in 1985 , 1990 , and 1995 . Cocoa intake was estimated from the consumption of cocoa-containing foods . RESULTS One third of the men did not use cocoa at baseline . The median cocoa intake among users was 2.11 g/d . After adjustment , the mean systolic blood pressure in the highest tertile of cocoa intake was 3.7 mm Hg lower ( 95 % confidence interval [ CI ] , -7.1 to -0.3 mm Hg ; P = .03 for trend ) and the mean diastolic blood pressure was 2.1 mm Hg lower ( 95 % CI , -4.0 to -0.2 mm Hg ; P = .03 for trend ) compared with the lowest tertile . During follow-up , 314 men died , 152 of cardiovascular diseases . Compared with the lowest tertile of cocoa intake , the adjusted relative risk for men in the highest tertile was 0.50 ( 95 % CI , 0.32 - 0.78 ; P = .004 for trend ) for cardiovascular mortality and 0.53 ( 95 % CI , 0.39 - 0.72 ; P < .001 ) for all-cause mortality . CONCLUSION In a cohort of elderly men , cocoa intake is inversely associated with blood pressure and 15-year cardiovascular and all-cause mortality BACKGROUND Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance . Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium . OBJECTIVE The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure , improve endothelial dysfunction , and ameliorate insulin resistance in subjects with essential hypertension . DESIGN We conducted a r and omized , placebo-controlled , double-blind , crossover trial of a flavanol-rich cocoa drink ( 150 mL twice a day , approximately 900 mg flavanols/d ) in individuals with essential hypertension ( n = 20 ) . Antihypertensive medications were discontinued before study enrollment . After a 7-d cocoa-free run-in period , cocoa or flavanol-poor placebo ( approximately 28 mg flavanols/d ) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm . Blood pressure was measured thrice weekly . At baseline and after each treatment period , we assessed insulin sensitivity ( hyperinsulinemic-isoglycemic glucose clamp ) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment ( Doppler ultrasound with or without microbubble contrast ) . RESULTS Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [ median percentage increase from baseline ( 25th-75th percentile ) : 8.3 ( 4.2 - 11.3 ) compared with 5.9 ( -0.3 to 9.6 ) ; P < 0.04 ] . Nevertheless , cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment , circulating plasma concentrations of adipocytokines , or endothelial adhesion molecules . CONCLUSIONS Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension . This trial was registered at clinical trials.gov as NCT00099476 AIMS To investigate the association of chocolate consumption with measured blood pressure ( BP ) and the incidence of cardiovascular disease ( CVD ) . METHODS AND RESULTS Dietary intake , including chocolate , and BP were assessed at baseline ( 1994 - 98 ) in 19 357 participants ( aged 35 - 65 years ) free of myocardial infa rct ion ( MI ) and stroke and not using antihypertensive medication of the Potsdam arm of the European Prospect i ve Investigation into Cancer and Nutrition . Incident cases of MI ( n = 166 ) and stroke ( n = 136 ) were identified after a mean follow-up of approximately 8 years . Mean systolic BP was 1.0 mmHg [ 95 % confidence interval ( CI ) -1.6 to -0.4 mmHg ] and mean diastolic BP 0.9 mmHg ( 95 % CI -1.3 to -0.5 mmHg ) lower in the top quartile compared with the bottom quartile of chocolate consumption . The relative risk of the combined outcome of MI and stroke for top vs. bottom quartiles was 0.61 ( 95 % CI 0.44 - 0.87 ; P linear trend = 0.014 ) . Baseline BP explained 12 % of this lower risk ( 95 % CI 3 - 36 % ) . The inverse association was stronger for stroke than for MI . CONCLUSION Chocolate consumption appears to lower CVD risk , in part through reducing BP . The inverse association may be stronger for stroke than for MI . Further research is needed , in particular r and omized trials CONTEXT Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies . Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure ( BP ) due to the action of the cocoa polyphenols , but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear . OBJECTIVE To determine effects of low doses of polyphenol-rich dark chocolate on BP . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled , investigator-blinded , parallel-group trial involving 44 adults aged 56 through 73 years ( 24 women , 20 men ) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors . The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006 . INTERVENTION Participants were r and omly assigned to receive for 18 weeks either 6.3 g ( 30 kcal ) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate . MAIN OUTCOME MEASURES Primary outcome measure was the change in BP after 18 weeks . Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide ( S-nitrosoglutathione ) and oxidative stress ( 8-isoprostane ) , and bioavailability of cocoa polyphenols . RESULTS From baseline to 18 weeks , dark chocolate intake reduced mean ( SD ) systolic BP by -2.9 ( 1.6 ) mm Hg ( P < .001 ) and diastolic BP by -1.9 ( 1.0 ) mm Hg ( P < .001 ) without changes in body weight , plasma levels of lipids , glucose , and 8-isoprostane . Hypertension prevalence declined from 86 % to 68 % . The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 ( 0.12 ) nmol/L ( P < .001 ) , and a dark chocolate dose result ed in the appearance of cocoa phenols in plasma . White chocolate intake caused no changes in BP or plasma biomarkers . CONCLUSIONS Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00421499 Background Evidence suggests that variations in fasting glucose and insulin amongst those without frank type 2 diabetes mellitus are important determinants of cardiovascular disease . However , the relative importance of variations in fasting insulin , glucose , and glycated haemoglobin as risk factors for cardiovascular disease in women without diabetes is unclear . Our aim was to determine the independent associations of fasting insulin , glucose , and glycated haemoglobin with coronary heart disease and stroke in older women . Methods and Findings We undertook a prospect i ve cohort study of 3,246 British women aged 60–79 y , all of whom were free of baseline coronary heart disease , stroke , and diabetes , and all of whom had fasting glucose levels below 7 mmol/l . Fasting insulin and homeostasis model assessment for insulin sensitivity ( HOMA-S ) were linearly associated with a combined outcome of coronary heart disease or stroke ( n = 219 events ) , but there was no association of fasting glucose or glycated haemoglobin with these outcomes . Results were similar for coronary heart disease and stroke as separate outcomes . The age , life-course socioeconomic position , smoking , and physical activity adjusted hazard ratio for a combined outcome of incident coronary heart disease or stroke per one st and ard deviation of fasting insulin was 1.14 ( 95 % CI 1.02–1.33 ) . Additional adjustment for other components of metabolic syndrome , low-density lipoprotein cholesterol , fasting glucose , and glycated haemoglobin had little effect on this result . Conclusions Our findings suggest that in women in the 60–79 y age range , insulin resistance , rather than insulin secretion or chronic hyperglycaemia , is a more important risk factor for coronary heart disease and stroke . Below currently used thresholds of fasting glucose for defining diabetes , neither fasting glucose nor glycated haemoglobin are associated with cardiovascular disease BACKGROUND Epidemiologic studies suggest that high flavonoid intake confers a benefit on cardiovascular outcome . Endothelial function , arterial stiffness , and wave reflections are important determinants of cardiovascular performance and are predictors of cardiovascular risk . METHODS The effect of flavonoid-rich dark chocolate ( 100 g ) on endothelial function , aortic stiffness , wave reflections , and oxidant status were studied for 3 h in 17 young healthy volunteers according to a r and omized , single-blind , sham procedure-controlled , cross-over protocol . Flow-mediated dilation ( FMD ) of the brachial artery , aortic augmentation index ( AIx ) , and carotid-femoral pulse wave velocity ( PWV ) were used as measures of endothelial function , wave reflections , and aortic stiffness , respectively . Plasma oxidant status was evaluated with measurement of plasma malondialdehyde ( MDA ) and total antioxidant capacity ( TAC ) . RESULTS Chocolate led to a significant increase in resting and hyperemic brachial artery diameter throughout the study ( maximum increase by 0.15 mm and 0.18 mm , respectively , P < .001 for both ) . The FMD increased significantly at 60 min ( absolute increase 1.43 % , P < .05 ) . The AIx was significantly decreased with chocolate throughout the study ( maximum absolute decrease 7.8 % , P < .001 ) , indicating a decrease in wave reflections , whereas PWV did not change to a significant extent . Plasma MDA and TAC did not change after chocolate , indicating no alterations in plasma oxidant status . CONCLUSIONS Our study shows for the first time that consumption of dark chocolate acutely decreases wave reflections , that it does not affect aortic stiffness , and that it may exert a beneficial effect on endothelial function in healthy adults . Chocolate consumption may exert a protective effect on the cardiovascular system ; further studies are warranted to assess any long-term effects CONTEXT The Framingham Heart Study produced sex-specific coronary heart disease ( CHD ) prediction functions for assessing risk of developing incident CHD in a white middle-class population . Concern exists regarding whether these functions can be generalized to other population s. OBJECTIVE To test the validity and transportability of the Framingham CHD prediction functions per a National Heart , Lung , and Blood Institute workshop organized for this purpose . DESIGN , SETTING , AND SUBJECTS Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infa rct ion . These functions were applied to 6 prospect ively studied , ethnically diverse cohorts ( n = 23 424 ) , including whites , blacks , Native Americans , Japanese American men , and Hispanic men : the Atherosclerosis Risk in Communities Study ( 1987 - 1988 ) , Physicians ' Health Study ( 1982 ) , Honolulu Heart Program ( 1980 - 1982 ) , Puerto Rico Heart Health Program ( 1965 - 1968 ) , Strong Heart Study ( 1989 - 1991 ) , and Cardiovascular Health Study ( 1989 - 1990 ) . MAIN OUTCOME MEASURES The performance , or ability to accurately predict CHD risk , of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts ' data . Comparisons included evaluation of the e quality of relative risks for st and ard CHD risk factors , discrimination , and calibration . RESULTS For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up . Among Japanese American and Hispanic men and Native American women , the Framingham functions systematic ally overestimated the risk of 5-year CHD events . After recalibration , taking into account different prevalences of risk factors and underlying rates of developing CHD , the Framingham functions worked well in these population s. CONCLUSIONS The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different setting s and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events This study investigated the effects of regular consumption of dark chocolate ( DC ) , rich in cocoa polyphenols , on plasma metabolites , hormones , and markers of oxidative stress after prolonged exhaustive exercise . Twenty active men cycled at 60 % maximal oxygen uptake ( VO2max ) for 1.5 hr , with the intensity increased to 90 % VO2max for a 30-s period every 10 min , followed by a ride to exhaustion at 90 % VO2max . In the 2 wk before exercise participants consumed 40 g of DC or an isocarbohydrate-fat control cocoa liquor-free chocolate ( CON ) twice daily and once 2 hr before exercise in a r and omized , counterbalanced , crossover design . Venous blood sample s were taken immediately before exercise , postexercise ( fixed duration ) , postexhaustion , and after 1 hr of recovery . F2-isoprostanes were significantly lower ( post hoc tests : p < .001 ) at exhaustion and after 1 hr of recovery with DC . Oxidized low-density lipoproteins were significantly lower with DC ( p < .001 ) both before and after exercise and at exhaustion . DC was also associated with ~21 % greater rises in free fatty acids during exercise ( main effect : p < .05 ) . Changes in circulating glucose , insulin , glucagon , cortisol , and interleukin (IL)-6 , IL-10 , and IL-1ra were unaffected by treatment . Time to exhaustion at 90 % VO2max was not significantly different between trials ( 398 ± 204 and 374 ± 194 s for DC and CON , respectively ) . These results suggest that regular DC intake is associated with reduced oxidative-stress markers and increased mobilization of free fatty acids after exercise but has no observed effect on exercise performance OBJECTIVES This study was design ed to assess the effect of flavanol-rich food on the circulating pool of bioactive nitric oxide ( NO ) and endothelial dysfunction in smokers . BACKGROUND Studies suggest that smoking-related vascular disease is caused by impaired NO synthesis and that diets rich in flavanols can increase bioactive NO in plasma . METHODS In smokers ( n = 11 ) , the effects of flavanol-rich cocoa on circulating NO species in plasma ( RXNO ) measured by reductive gas-phase chemiluminescence and endothelial function as assessed by flow-mediated dilation ( FMD ) were characterized in a dose-finding study orally administering cocoa containing 88 to 370 mg flavanols and in a r and omized double-blind crossover study using 100 ml cocoa drink with high ( 176 to 185 mg ) or low ( < 11 mg ) flavanol content on two separate days . In addition to cocoa drink , ascorbic acid and NO-synthase inhibitor L-NMMA ( n = 4 ) were applied . RESULTS There were significant increases in RXNO ( 21 + /- 3 nmol/l to 29 + /- 5 nmol/l ) and FMD ( 4.5 + /- 0.8 % to 6.9 + /- 0.9 % , each p < 0.05 ) at 2 h after ingestion of 176 to 185 mg flavanols , a dose potentially exerting maximal effects . These changes correlated with increases in flavanol metabolites . Cocoa-associated increases in RXNO and FMD were reversed by L-NMMA . Ascorbic acid had no effect . CONCLUSIONS The circulating pool of bioactive NO and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink . The increase in circulating NO pool may contribute to beneficial vascular health effects of flavanol-rich food Endothelial dysfunction characterizes many disease states including sub clinical atherosclerosis . The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal , healthy individuals when administered either acutely or over a period of several days , or weeks . Women experience increased risk for cardiovascular disease after menopause , which can be associated with endothelial dysfunction . Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known . The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women . Thirty-two postmenopausal hypercholesterolemic women were r and omly assigned to consume a high-flavanol cocoa beverage ( high cocoa flavanols (CF)—446 mg of total flavanols ) , or a low-flavanol cocoa beverage ( low CF—43 mg of total flavanols ) for 6 weeks in a double-blind study ( n=16 per group ) . Endothelial function was determined by brachial artery-reactive hyperemia . Plasma was analyzed for lipids ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol ) , hormones ( follicle-stimulating hormone ) , total nitrate/nitrite , activation of cellular adhesion markers ( vascular cell adhesion molecule 1 , intercellular adhesion molecule 1 , E-Selectin , P-Selectin ) , and platelet function and reactivity . Changes in these plasma markers were then correlated to brachial reactivity . Brachial artery hyperemic blood flow increased significantly by 76 % ( P<0.05 vs. baseline ) after the 6-week cocoa intervention in the high CF group , compared with 32 % in the low CF cocoa group ( P = ns vs. baseline ) . The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated ( r2=0.8 ) with a significant decrease ( 11 % ) in plasma levels of soluble vascular cell adhesion molecule-1 . Similar responses were not observed after chronic use of low CF . There were no significant differences between high and low CF in other biochemical markers and parameters measured . This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women . In addition , our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity OBJECTIVES Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients . BACKGROUND Even in fully medicated diabetic patients , overall prognosis is unfavorable due to deteriorated cardiovascular function . Based on epidemiological data , diets rich in flavanols are associated with a reduced cardiovascular risk . METHODS In a feasibility study with 10 diabetic patients , we assessed vascular function as flow-mediated dilation ( FMD ) of the brachial artery , plasma levels of flavanol metabolites , and tolerability after an acute , single-dose ingestion of cocoa , containing increasing concentrations of flavanols ( 75 , 371 , and 963 mg ) . In a subsequent efficacy study , changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day , thrice-daily dietary intervention with either flavanol-rich cocoa ( 321 mg flavanols per dose ) or a nutrient-matched control ( 25 mg flavanols per dose ) . Both studies were undertaken in a r and omized , double-masked fashion . Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites , respectively . RESULTS A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD ( at 2 h : from 3.7 + /- 0.2 % to 5.5 + /- 0.4 % , p < 0.001 ) . A 30-day , thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30 % ( p < 0.0001 ) , while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study . Treatment was well tolerated without evidence of tachyphylaxia . Endothelium-independent responses , blood pressure , heart rate , and glycemic control were unaffected . CONCLUSIONS Diets rich in flavanols reverse vascular dysfunction in diabetes , highlighting therapeutic potentials in cardiovascular disease 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 Consumption of flavanol-containing cocoa products has been shown to lower blood pressure ( BP ) , but the minimum dose required to reduce BP is not known . This study aim ed to examine the effect of three different doses of cocoa flavanols ( CF ) on 24-h mean arterial BP . Twenty four hour ambulatory BP ( 24-ABP ) monitoring was performed in 32 men and 20 postmenopausal women with untreated mild hypertension ( seated clinic BP > 130/85 and < 160/100 mm Hg ) . Participants were r and omized and instructed to consume daily a reconstituted cocoa beverage containing 33 , 372 , 712 or 1052 mg day−1 of CF for 6 weeks in a double-blind , parallel comparison . Seated clinic BP and 24-h ABP were measured at 0 , 3 and 6 weeks . Seated clinic BP did not change during the study period . There were significant reductions in 24-h systolic ( 5.3±5.1 mm Hg ; P=0.001 ) , diastolic ( 3±3.2 mm Hg ; P=0.002 ) and mean arterial BP ( 3.8±3.2 mm Hg ; P=0.0004 ) at the 1052 mg day−1 CF only . No reduction in BP was seen at any other dose . No evidence of dose – response was seen in this experiment . The highest dose of 1052 mg CF per day was found to significantly lower BP . These results support previous evidence for CF to lower BP , however more research is needed to establish the most effective dose and food matrix OBJECTIVES In patients with coronary artery disease ( CAD ) medically managed according to currently accepted guidelines , we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells ( CACs ) . BACKGROUND Dietary flavanols can improve endothelial dysfunction . The CACs , also termed endothelial progenitor cells , are critical for vascular repair and maintenance of endothelial function . METHODS In a r and omized , controlled , double-masked , cross-over trial , 16 CAD patients ( 64+/-3 years of age ) received a dietary high-flavanol intervention ( HiFI [ 375 mg ] ) and a macronutrient- and micronutrient-matched low-flavanol intervention ( LoFI [ 9 mg ] ) twice daily in r and om order over 30 days . RESULTS Endothelium-dependent vasomotor function , as measured by flow-mediated vasodilation of the brachial artery , improved by 47 % in the HiFI period compared with the LoFI period . After HiFI , the number of CD34+/KDR+-CACs , as measured by flow cytometry , increased 2.2-fold as compared with after LoFI . The CAC functions , as measured by the capacity to survive , differentiate , proliferate , and to migrate were not different between the groups . The HiFI led to a decrease in systolic blood pressure ( mean change over LoFI : -4.2+/-2.7 mm Hg ) , and increase in plasma nitrite level ( mean change over LoFI : 74+/-32 nM ) . Applying a mixed-effects linear regression model , the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs . CONCLUSIONS Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs . ( Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients : Interaction Between Endothelial Progenitor Cells , Reactivity of Micro- and Macrocirculation ; NCT00553774 ) BACKGROUND Studies of cocoa suggest an array of cardiovascular benefits ; however , the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function ( EF ) have yet to be established . METHODS 44 adults ( BMI 25 - 35 kg/m2 ) participated in a r and omized , controlled , crossover trial . Participants were r and omly assigned to a treatment sequence : sugar-free cocoa beverage , sugar-sweetened cocoa beverage , and sugar-sweetened cocoa-free placebo . Treatments were administered daily for 6 weeks , with a 4-week washout period . RESULTS Cocoa ingestion improved EF measured as flow-mediated dilation ( FMD ) compared to placebo ( sugar-free cocoa : change , 2.4 % [ 95 % CI , 1.5 to 3.2 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 3.2 % [ 95 % CI , 1.8 to 4.6 ] ; p<0.001 and sugar-sweetened cocoa : change , 1.5 % [ 95 % CI , 0.6 to 2.4 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 2.3 % [ 95 % CI , 0.9 to 3.7 ] ; p=0.002 ) . The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater , but not significantly . Other biomarkers of cardiac risk did not change appreciably from baseline . BMI remained stable throughout the study . CONCLUSIONS Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk , and does not cause weight gain . Sugar-free preparations may further augment endothelial function BACKGROUND The absorption of cocoa flavanols in the small intestine is limited , and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota . OBJECTIVE We assessed the prebiotic potential of cocoa flavanols in a r and omized , double-blind , crossover , controlled intervention study . DESIGN Twenty-two healthy human volunteers were r and omly assigned to either a high-cocoa flavanol ( HCF ) group ( 494 mg cocoa flavanols/d ) or a low-cocoa flavanol ( LCF ) group ( 23 mg cocoa flavanols/d ) for 4 wk . This was followed by a 4-wk washout period before volunteers crossed to the alternant arm . Fecal sample s were recovered before and after each intervention , and bacterial numbers were measured by fluorescence in situ hybridization . A number of other biochemical and physiologic markers were measured . RESULTS Compared with the consumption of the LCF drink , the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial ( P < 0.01 ) and lactobacilli ( P < 0.001 ) population s but significantly decreased clostridia counts ( P < 0.001 ) . These microbial changes were paralleled by significant reductions in plasma triacylglycerol ( P < 0.05 ) and C-reactive protein ( P < 0.05 ) concentrations . Furthermore , changes in C-reactive protein concentrations were linked to changes in lactobacilli counts ( P < 0.05 , R(2 ) = -0.33 for the model ) . These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments . CONCLUSION This study shows , for the first time to our knowledge , that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans , which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods . This trial was registered at clinical trials.gov as NCT01091922 |
11,254 | 28,992,533 | We found that functional abnormalities in OCD cluster within cortico-striatal thalamic circuits .
Within these circuits , the abnormalities identified showed significant dependence on the affective or non-affective nature of the tasks employed as circuit probes .
In studies using affective tasks , patients overactivated regions involved in salience , arousal and habitual responding ( anterior cingulate cortex , insula , cau date head and putamen ) and underactivated regions implicated in cognitive and behavioral control ( medial prefrontal cortex , posterior cau date ) .
In studies using non-affective cognitive tasks , patients overactivated regions involved in self-referential processing ( precuneus , posterior cingulate cortex ) and underactivated subcortical regions that support goal -directed cognition and motor control ( pallidum , ventral anterior thalamus , posterior cau date ) .
The overall pattern suggests that OCD-related brain dysfunction involves increased affective and self-referential processing , enhanced habitual responding and blunted cognitive control | Obsessive compulsive disorder ( OCD ) is characterized by intrusive thoughts and repetitive ritualistic behaviors and has been associated with diverse functional brain abnormalities .
We sought to synthesize current evidence from functional magnetic resonance imaging ( fMRI ) studies and examine their alignment to pathogenetic models of OCD . | This functional magnetic resonance imaging study investigated the disgust- and fear-reactivity of patients suffering from obsessive-compulsive disorder ( OCD ) . Ten OCD patients were scanned while viewing blocks of pictures showing OCD triggers from their personal environment and OCD-irrelevant disgust-inducing , fear-inducing and neutral scenes . Afterwards , the patients rated the intensity of the induced disgust , fear and OCD symptoms . The responses were compared with those of 10 healthy control subjects . The disorder-relevant pictures provoked intense OCD symptoms in the clinical group associated with increased activation in the bilateral prefrontal cortex , the left insula , the right supramarginal gyrus , the left cau date nucleus and the right thalamus . The patients gave higher disgust and fear ratings than the controls for all aversive picture categories . Neural responses towards the disorder-irrelevant disgusting and fear-inducing material included more pronounced insula activation in patients than controls . Summarizing , photos of individual OCD-triggers are an effective means of symptom provocation and activation of the fronto-striato-thalamo-parietal network . The increased insular reactivity of OCD patients during all aversive picture conditions might mirror their susceptibility to experience negative somatic states In subjects with obsessive-compulsive disorder ( OCD ) , lower pre-treatment metabolism in the right orbitofrontal cortex ( OFC ) and anterior cingulate gyrus ( AC ) has been associated with a better response to clomipramine . We sought to determine pre-treatment metabolic predictors of response to behavioral therapy ( BT ) vs. pharmacotherapy in subjects with OCD . To do this , [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine . A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC , AC , and cau date by treatment response ( change in Yale-Brown Obsessive-Compulsive Scale ) in the larger BT group . Left OFC metabolism ( normalized to the ipsilateral hemisphere ) alone was selected as predicting treatment response in the BT-treated group ( F = 6.07 , d.f . = 1,17 , P = 0.025 ) . Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group ( tau = 0.35 , P = 0.04 ) , but worse outcome ( tau = -0.57 , P = 0.03 ) in the fluoxetine-treated group . These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication BACKGROUND Cognitive behavioral therapy ( CBT ) with exposure and response prevention ( ERP ) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder ( OCD ) . However , little is known about the impact of CBT on frontostriatal dysfunctioning , known to be the neuronal correlate of OCD . METHOD A probabilistic reversal learning ( RL ) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging ( fMRI ) experiment . Patients were scanned before and after intensive CBT , controls twice at comparable intervals . RESULTS Strategy change within the RL task involved activity in a broad frontal network in patients and controls . No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons . However , a re analysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects . A group by time effect was found in the cau date nucleus , demonstrating increased activity for patients over the course of time . Patients with greater clinical improvement , reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale ( YBOCS ) scores , showed more stable activation in the pallidum . CONCLUSIONS Although these findings are preliminary and need to be replicated in larger sample s , they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD , the cau date nucleus and the pallidum |
11,255 | 26,220,460 | Findings revealed that moral distress negatively affects clinicians ' wellbeing and job retention . | Moral distress occurs when professionals can not carry out what they believe to be ethically appropriate actions .
This review describes the publication trend on moral distress and explores its relationships with other constructs . | Moral distress is the knowledge of the ethically appropriate action to take but the inability to act upon it . This phenomenon is one experienced in the critical care setting . To help staff members cope with moral distress , a team conducted workshops at one facility to help the staff identify and cope with this distress . The workshop consisted of discussion s of distressing situations in the intensive care unit , didactic information on moral distress , formulation of an individual plan to reduce stress , and strategies to deal with moral distress in the intensive care unit . This article discusses the workshop and its effect on participants ' coping with moral distress Moral distress is described as the painful feelings and psychological disequilibrium when a person believes she knows the morally right action to take and is unable to carry it out because of external or internal constraints . It has been studied in intensive care unit ( ICU ) nurses , but to the best of our knowledge not in burn ICU nurses . A pilot study was performed to gather initial data on moral distress among nurses treating burn victims . Findings from an intervention aim ed at decreasing the level of moral distress in these nurses are reported . Nurses ( n = 13 ) were recruited from one U.S. burn ICU and were r and omized into two groups . A separate sample pretest post-test design was used . Group A completed the Moral Distress Scale-Revised ( MDS-R ) and Self-efficacy ( SE ) Scale before a 4-week educational intervention involving weekly 60-minute sessions , and Group B completed both scales afterward . Participants also completed written evaluations after each session . The MDS-R and SE Scale were readministered to both groups 6 weeks after the intervention was completed . Given the size and distribution of the sample , nonparametric data analyses were used . The MDS-R median score for Group B ( 92.0 ) was significantly different statistically from Group A ( 40.5 ) with P = .032 directly after the intervention was completed . No significant difference was found in the median SE scores between Group A ( 34.5 ) and Group B ( 34.0 ; P = .616 ) . The median for Group B was 69 and Group A was 60.5 ( P = .775 ) . At the 6-week follow up , the difference between the two groups was no longer observed . Defining and discussing moral distress may have contributed to increased awareness and higher levels of moral distress in Group B directly postintervention . The changes in moral distress levels postintervention and at the 6-week follow up highlight the need to examine the intervention in a larger sample Objective In this study , we tested an exp and ed model of Kanter ’s structural empowerment , which specified the relationships among structural and psychological empowerment , job strain , and work satisfaction . Background Strategies proposed in Kanter ’s empowerment theory have the potential to reduce job strain and improve employee work satisfaction and performance in current restructured healthcare setting s. The addition to the model of psychological empowerment as an outcome of structural empowerment provides an underst and ing of the intervening mechanisms between structural work conditions and important organizational outcomes . Methods A predictive , nonexperimental design was used to test the model in a r and om sample of 404 Canadian staff nurses . The Conditions of Work Effectiveness Question naire , the Psychological Empowerment Question naire , the Job Content Question naire , and the Global Satisfaction Scale were used to measure the major study variables . Results Structural equation modelling analyses revealed a good fit of the hypothesized model to the data based on various fit indices ( χ2 = 1140 , df = 545 , χ2/df ratio = 2.09 , CFI = 0.986 , RMSEA = 0.050 ) . The amount of variance accounted for in the model was 58 % . Staff nurses felt that structural empowerment in their workplace result ed in higher levels of psychological empowerment . These heightened feelings of psychological empowerment in turn strongly influenced job strain and work satisfaction . However , job strain did not have a direct effect on work satisfaction . Conclusions These results provide initial support for an exp and ed model of organizational empowerment and offer a broader underst and ing of the empowerment process We prospect ively studied the relationship between interdisciplinary collaboration and patient outcomes in the medical intensive care unit ( MICU ) using nurses ' and residents ' reports of amount of collaboration involved in making decisions about transferring patients from the MICU to a unit with a less intense level of care . Either readmission to the MICU or death was considered a negative patient outcome . Nurses ' reports of collaboration were significantly ( p = 0.02 ) and positively associated with patient outcome , controlling for severity of illness . Patient predicted risk of negative outcome decreased from 16 % , when the nurse reported no collaboration in decision making , to 5 % when the process was fully collaborative . There was an interaction of collaboration with availability of alternative choices in the transfer decision-making situation . When alternatives were available , collaboration was more strongly associated with patient outcome . There was no significant relationship between residents ' reports of collaboration and patient outcomes . The correlation between amount of collaboration reported by nurses and residents about the same decisions was quite low ( r = 0.10 ) Study purpose was to describe critical care nurses ' levels of moral distress and the effects of that distress on their professional practice environment . A descriptive , correlational , prospect i ve , survey design was used . The intensity of moral distress was inversely related to physician/nurse collegial relationships and the frequency of moral distress was inversely related to all aspects of the professional practice environment except foundations for quality of care . It is important to monitor the frequency of moral distress . Strategies to improve the nurse 's sense of control over practice , teamwork , communication , and autonomy need to be developed and tested in future research Moral distress is a phenomenon of increasing concern in nursing practice , education and research . Previous research has suggested that moral distress is associated with perceptions of ethical climate , which has implication s for nursing practice and patient outcomes . In this study , a r and omly selected sample of registered nurses was surveyed using Corley ’s Moral Distress Scale and Olson ’s Hospital Ethical Climate Survey ( HECS ) . The registered nurses reported moderate levels of moral distress intensity . Moral distress intensity and frequency were found to be inversely correlated with perceptions of ethical climate . Each of the HECS factors ( peers , patients , managers , hospitals and physicians ) was found to be significantly correlated with moral distress . Based on these findings , we highlight insights for practice and future research that are needed to enhance the development of strategies aim ed at improving the ethical climate of nurses ’ workplaces for the benefit of both nurses and patients The purpose of this study was to describe Finnish ICU nurses ' ( n=172 ) experiences of autonomy in their work . The research was carried out as part of a project concerned with empowerment in intensive care nursing . Viewed from a psychological perspective , empowerment is understood as referring to the ability to make goal -directed decisions and to take action towards meeting the goals set out . Autonomy , then , is seen as part of empowerment . The data were collected with a structured question naire specially design ed for this study . The r and om sample was drawn from 31 Finnish adult intensive care units . The respondents were registered nurses working in eight adult intensive care units . The data were analysed using statistical methods . Autonomy was defined as being composed of three bases : knowledge base ( independence , right and responsibility in decision-making ) , action base ( independence , right and responsibility in actions ) and value base ( independence , right and responsibility in values ) . The majority of the respondents felt they had more autonomy in decision-making and actions concerning patient care than in decision-making and actions concerning the intensive care unit as a whole . Autonomy usually increased with work experience . Work will be continued to study the autonomy of nurses in different health care organisations in Finl and |
11,256 | 23,397,183 | Non-EBIs had multiple method ological limitations ; the most common was not finding a significant positive effect .
Compared to EBIs , non-EBIs were less likely to use peer intervention deliverers , include sexual communication in their interventions , and intervene at the community level . | Gay , bisexual , and other men who have sex with men ( MSM ) are disproportionately affected by HIV but few MSM-specific evidence -based interventions ( EBIs ) have been identified for this vulnerable group .
We conducted a systematic review to identify reasons for the small number of EBIs for MSM . | In a r and omized trial of a behavioral intervention among substance-using men who have sex with men , aim ed at reducing sexual risk behavior , Mansergh and colleagues fail to find evidence of a reduction in risk from the intervention Numerous herpesvirus infections are associated with clinical ly relevant outcomes as well as an accelerated HIV replication rate and subsequent disease progression . Stress management interventions mayimprovemarkersofcellularimmunecontroloverlatent herpesvirus infections and these changes appear to be mediated by perceptions of increased social support availability . We examined the effects ofagroup-based cognitive behavioral stress management ( CBSM ) intervention on distress , dysphoria , perceived socialsupport , and herpesvirus immunoglobulin G ( IgG ) antibody titers during the 6to 12 months following the intervention . Of those who were initially r and omized , 49 HIV-infected men were followed during the 6-to 12-month period after r and omization to either a 10-week CBSM intervention ( n=31 ) or amodified wait-list control condition ( n = 18 ) . Measures of distress , dysphoria , social support , and blood sample s for herpesvirus Ig Gtiters were taken at baseline , immediately following CBSM and at-6-to 12-month follow-up . Men in CBSM displayed maintenance of previously observed intervention effects on dysphoria , reliable alliance support , and herpesvirus IgG antibody titers ( i.e. , Epstein-Barr virus capsid antigen ; EBV-VCA ) . Intervention-related changes in EBV-VCA were unrelated to changes in lymphocyte subsets ( i.e. , CD4 + , CD8 + , and CD4+:CD8 + ) or changes in measures of dysphoria and social support during the investigation period . Data indicate that HIV-infected men participating in a CBS Mintervention maintain better psychosocial status and immunologic control of latent EBV infection up to 1 year after its conclusion BACKGROUND Effective interventions are needed to prevent acquisition of HIV infection in men who have sex with men . To date , no behavioural interventions specifically for this risk group have been tested with HIV infection as the primary outcome . METHODS This multisite two-group r and omised controlled phase IIb trial tested the efficacy of a behavioural intervention in preventing HIV infection among 4295 men who have sex with men . The experimental intervention consisted of ten one-on-one counselling sessions followed by maintenance sessions every 3 months . The st and ard condition was twice-yearly Project RESPECT individual counselling . Twice-yearly follow-up visits included testing for HIV antibody and assessment of behavioural outcomes . FINDINGS The rate of acquisition of HIV infection was 18.2 % ( 95 % CI -4.7 to 36.0 ) lower in the intervention group than the st and ard group . Adjustment for baseline covariates attenuated the intervention effect to 15.7 % ( -8.4 to 34.4 ) . The effect was more favourable in the first 12 - 18 months of follow-up . The occurrence of unprotected receptive anal intercourse with HIV-positive and unknown-status partners was 20.5 % ( 10.9 to 29.0 ) lower in the intervention than in the st and ard group . INTERPRETATION The results from the primary analyses allow us to rule out that the experimental intervention is associated with a 35 % lower rate of HIV acquisition than in the st and ard group . The overall estimate of a difference of 18.2 % , more favourable estimates of effect in the first 12 - 18 months , and similar effects on risk behaviours suggest that prevention of HIV infection among men who have sex with men by a behavioural intervention is feasible . Further work should be done to develop more effective interventions Background : Brief and low-burden HIV risk reduction counseling interventions are needed for population s at greatest risk for HIV infection . Purpose : This r and omized controlled trial tested a brief theory-based counseling intervention delivered entirely over the telephone for men who engage in unprotected intercourse with men . Methods : Participants received either risk reduction counseling that included information , motivational enhancement and behavior skills building , or brief HIV education counseling . A total of 319 participants completed follow-up assessment s over a 10-month period . Descriptive and r and om effects mixed models are used to evaluate findings . Results : Results demonstrate that a brief telephone intervention can reach and engage high-risk men in risk reduction counseling . Nearly one third of participants identified as men of color ; the median age was 33 years . Participants in both counseling conditions increased their motivation and behavioral skills to practice safer sex and reduced their number of sex partners and frequencies of engaging in unprotected anal sex over the study observation period . However , there were few differences between intervention conditions . Conclusions : The effects of repeated measurement reactivity and brief interpersonal consciousness raising may account for the lack of differences between counseling conditions and the decrease in risk for all participants over time BACKGROUND As many as one in three HIV-positive people continue unprotected sexual practice s after learning that they are HIV infected . This article reports the outcomes of a theory-based intervention to reduce risk of HIV transmission for people living with HIV infection . METHODS Men ( n=233 ) and women ( n=99 ) living with HIV-AIDS were r and omly assigned to receive either ( 1 ) a five-session group intervention focused on strategies for practicing safer sexual behavior , or ( 2 ) a five-session , contact-matched , health-maintenance support group ( st and ard-of-care comparison ) . Participants were followed for 6 months post-intervention . RESULTS The intervention to reduce risk of HIV transmission result ed in significantly less unprotected intercourse and greater condom use at follow-up . Transmission-risk behaviors with non-HIV-positive sexual partners and estimated HIV transmission rates over a 1-year horizon were also significantly lower for the behavioral risk-reduction intervention group . CONCLUSIONS This study is among the first to demonstrate successful HIV-transmission risk reduction result ing from a behavioral intervention tailored for HIV-positive men and women At the time of this writing , no r and omized controlled trial ( RCT ) of an intervention to reduce unsafe sex among Latino gay and bisexual men ( LGBM ) had been published . We report the results of an RCT conducted in New York City in which 180 LGBM were assigned either to an intervention developed specifically for this population or to a wait-list control group . The intervention was based on empowerment theory and used factors identified in prior research as determinants of unsafe sex . By eligibility criteria , all men had engaged in unprotected anal intercourse ( UAI ) within two months of the baseline assessment . At first ( two months ) and second ( six months later ) follow-up assessment s , approximately half of the men in the experimental group reported no UAI . Yet , a similar proportion of the control group also reported no UAI . Baseline data indicate that although the men had been the subject of social oppression and sexual prejudice ( homophobia ) , they did not feel disempowered , externally controlled or fatalistic , and they reported self-efficacy and intentionality to enact safer sex . Lessons learned are discussed , as well as notes of caution for future research employing a similar conceptual framework Objective : To test the efficacy of brief , safer-sex counseling by medical providers of HIV-positive patients during medical visits . Setting : Six HIV clinics in California . Design : Clinics were r and omized to intervention arms evaluated with cohorts of r and omly selected patients measured before and after the intervention . Participants : Five-hundred and eighty-five HIV-positive persons , sexually active prior to enrollment . Interventions : Prevention counseling from medical providers supplemented with written information . Two clinics used a gain-framed approach ( positive consequences of safer-sex ) , two used a loss-frame approach ( negative consequences of unsafe sex ) , and two were attention-control clinics ( medication adherence ) . Interventions were given to all patients who attended the clinics . Outcome measure : Self-reported unprotected anal or vaginal intercourse ( UAV ) . Results : Among participants who had two or more sex partners at baseline , UAV was reduced 38 % ( P < 0.001 ) among those who received the loss-frame intervention . UAV at follow-up was significantly lower in the loss-frame arm [ odds ratio ( OR ) , 0.42 ; 95 % confidence interval ( CI ) , 0.19–0.91 ; P = 0.03 ] compared with the control arm . Using generalized estimating equations ( GEE ) to adjust for clustering did not change the conclusions ( OR , 0.34 ; 95 % CI , 0.24–0.49 ; P = 0.0001 ) . Similar results were obtained in participants with casual partners at baseline . No effects were seen in participants with only one partner or only a main partner at baseline . No significant changes were seen in the gain-frame arm . Conclusions : Brief provider counseling emphasizing the negative consequences of unsafe sex can reduce HIV transmission behaviors in HIV-positive patients presenting with risky behavioral profiles Objectives : To evaluate the effects of an enhanced peer-led intervention on transmission risk behavior and serostatus disclosure of HIV-seropositive gay and bisexual men . Design : A r and omized intervention trial . Methods : HIV-seropositive gay and bisexual men were recruited from New York City and San Francisco and were r and omly assigned to either a st and ard or an enhanced intervention . The st and ard intervention consisted of one session that provided safer sex information . The enhanced intervention consisted of six sessions and included safer sex information , interactive learning activities , and discussion groups that were facilitated by HIV-seropositive peers . Participants completed audio computer-assisted self interview ( A-CASI ) assessment s at baseline and 3 and 6-month follow-ups . Optional testing for sexually transmitted infections was offered at baseline and the 6-month follow-up . Results : A total of 811 participants met the inclusion criteria for outcome analyses . Of these , 85 and 90 % were retained for the 3 and 6-month follow-ups , respectively . Compared with the st and ard intervention , fewer men assigned to the enhanced intervention reported unprotected receptive anal intercourse with a negative or unknown-serostatus partner at 3 months ( 21 versus 26 % , P < 0.05 ) . However , there were no other significant differences in transmission risk or serostatus disclosure at 3 or 6 months . Conclusion : The enhanced intervention was associated with only a limited reduction in transmission risk at 3 months relative to the st and ard intervention . The characteristics of the intervention that may have reduced its efficacy are identified and directions for future research are suggested There is an increasing interest in developing interventions for HIV and STD prevention that can be delivered on the Internet . However , we know little about what it takes to identify , recruit and retain participants in interventions so that we can test their efficacy and effectiveness . Objectives for this investigation were to evaluate rates of recruitment and retention in an Internet-based r and omized controlled trial ( RCT ) to increase sexually transmitted disease ( STD ) prevention among men who have sex with men ( MSM ) . The Smart Sex Quest study was a RCT conducted online . Eligible participants were MSM , at least 18 years old and US residents . After completing a baseline risk assessment , participants were exposed to tailored or control messages and asked to return to the site at three months for a follow-up interview . From January 2002 through June 2003 , 3,625 persons logged on as potential study participants ; of these , 563 were not eligible , while 1,286 left the site without filling out a baseline survey . Complete baseline data were available for 1,776 participants , all of whom were eligible to complete a follow-up . Complete follow-up data were available for 270 ( 15.2 % ) participants . While the Internet is a valuable tool for conducting research , conducting this longitudinal research online was severely affected by a loss to follow-up , and analyzing outcome data was hampered by significant differences between those who did and did not complete the study . Alternate ways to recruit for and evaluate online trials must be considered To the extent that men who have sex with men ( MSM ) use the Internet , it serves as a promising medium for behavioral intervention . The present study sought to investigate the efficacy of a web-based skills training and motivational intervention in a r and omized trial ( N = 112 ) conducted completely online . After a detailed assessment , MSM were r and omly assigned to an online intervention or a control website . The experimental intervention consisted of risk assessment and feedback , motivational exercises , skills training , and education while the control intervention focused on relaxation skills . Follow-up data were collected 3 months later and analyzed with repeated- measures MANOVA . Although both groups evidence d across-the-board reductions in unprotected sex , perhaps due to the detailed assessment , the experimental group showed greater reductions with the riskiest partners , those of positive or unknown serostatus . Thus , this study gives preliminary evidence that a brief web-based intervention offering cognitive behavioral skills training and motivational enhancement can effectively reduce sexual risk in MSM Behavior change can curtail the spread of acquired immune deficiency syndrome ( AIDS ) . In this study , 104 gay men with a history of frequent AIDS high-risk behavior completed self-report , self-monitoring , and behavioral measures related to AIDS risk . The sample was r and omly divided into experimental and waiting-list control groups . The experimental intervention provided AIDS risk education , cognitive-behavioral self-management training , sexual assertion training , and attention to the development of steady and self-affirming social supports . Experimental group participants greatly reduced their frequency of high-risk sexual practice s and increased behavioral skills for refusing sexual coercions , AIDS risk knowledge , and adoption of " safer sex " practice s. Change was maintained at the 8-month follow-up Summary HIV risky behaviors and health practice s were examined among young people living with HIV ( YPLH ) in Los Angeles , San Francisco , and New York over 15 months in response to receiving a preventive intervention . YPLH aged 16 to 29 years ( n = 175 ; 26 % black and 42 % Latino ; 69 % gay men ) were r and omly assigned to a 3-module intervention totaling 18 sessions delivered by telephone , in person , or a delayed-intervention condition . Intention-to-treat analyses found that the in-person intervention result ed in a significantly higher proportion of sexual acts protected by condoms overall and with HIV-seronegative partners . Pre- and postanalyses of YPLH in the delayed-intervention condition alone found that YPLH tended to have fewer sexual partners , used fewer drugs , reported less emotional distress , and decreased their use of antiretroviral therapies . Prevention programs can be delivered in alternative formats while retaining efficacy . When YPLH are using hard drugs , drug treatment may be needed before delivery of preventive interventions Background Methamphetamine use is associated with HIV acquisition and transmission among men who have sex with men ( MSM ) . Contingency management ( CM ) , providing positive reinforcement for drug abstinence and withholding reinforcement when abstinence is not demonstrated , may facilitate reduced methamphetamine use and sexual risk . We compared CM as a st and -alone intervention to a minimal intervention control to assess the feasibility of conducting a larger , more definitive trial of CM ; to define the frequency of behavioral outcomes to power such a trial ; and , to compute preliminary estimates of CM 's effectiveness . Methods We r and omly assigned 127 MSM from Seattle , WA who use methamphetamine to receive a 12-week CM intervention ( n = 70 ) or referral to community re sources ( n = 57 ) . Results Retention at 24 weeks was 84 % . Comparing consecutive study visits , non-concordant UAI declined significantly in both study arms . During the intervention , CM and control participants were comparably likely to provide urine sample s containing methamphetamine ( adjusted relative risk [ aRR ] = 1.09 ; 95%CI : 0.71 , 1.56 ) and to report non-concordant UAI ( aRR = 0.80 ; 95%CI : 0.47 , 1.35 ) . However , during post-intervention follow-up , CM participants were somewhat more likely to provide urine sample s containing methamphetamine than control participants ( aRR = 1.21 ; 95%CI : 0.95 , 1.54 , P = 0.11 ) . Compared to control participants , CM participants were significantly more likely to report weekly or more frequent methamphetamine use and use of more than eight quarters of methamphetamine during the intervention and post-intervention periods . Conclusions While it is possible to enroll and retain MSM who use methamphetamine in a trial of CM conducted outside drug treatment , our data suggest that CM is not likely to have a large , sustained effect on methamphetamine use . Trial Registration Clinical Trials.gov Identifier The Internet may be important for delivering human immunodeficiency virus ( HIV ) risk reduction to men who have sex with men ( MSM ) in rural areas . This r and omized control trial ( RCT ) tested the acceptability and efficacy of an Internet-delivered HIV risk-reduction intervention . Two modules include a conversation between an HIV-negative man and an HIV-positive man , with interactive graphics . Ninety men were r and omly assigned to intervention or wait-list control and 79 % completed the study . An ' intent-to-treat ' model was used . HIV/acquired immune deficiency syndrome ( AIDS ) knowledge , self-efficacy and outcome expectancies increased after participating in the intervention , and changes were maintained at 1-week follow-up . Participants said they would participate again . This RCT provides support for the acceptability and efficacy of the Internet for delivering HIV prevention messages to rural MSM Background Reducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission . Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks , it is unknown how to best provide “ prevention with positives ” in clinical setting s. Positive Choice , an interactive , patient-tailored computer program , was developed in the United States to improve clinic-based assessment and counseling for risky behaviors . Methodology and Findings We conducted a parallel groups r and omized controlled trial ( December 2003–September 2006 ) at 5 San Francisco area outpatient HIV clinics . Eligible patients ( HIV-positive English-speaking adults ) completed an in-depth computerized risk assessment . Participants reporting substance use or sexual risks ( n = 476 ) were r and omized in stratified blocks . The intervention group received tailored risk-reduction counseling from a “ Video Doctor ” via laptop computer and a printed Educational Worksheet ; providers received a Cueing Sheet on reported risks . Compared with control , fewer intervention participants reported continuing illicit drug use ( RR 0.81 , 95 % CI : 0.689 , 0.957 , p = 0.014 at 3 months ; and RR 0.65 , 95 % CI : 0.540 , 0.785 , p<0.001 at 6 months ) and unprotected sex ( RR 0.88 , 95 % CI : 0.773 , 0.993 , p = 0.039 at 3 months ; and RR 0.80 , 95 % CI : 0.686 , 0.941 , p = 0.007 at 6 months ) . Intervention participants reported fewer mean days of ongoing illicit drug use ( -4.0 days vs. -1.3 days , p = 0.346 , at 3 months ; and -4.7 days vs. -0.7 days , p = 0.130 , at 6 months ) than did controls , and had fewer casual sex partners at ( −2.3 vs. −1.4 , p = 0.461 , at 3 months ; and −2.7 vs. −0.6 , p = 0.042 , at 6 months ) . Conclusions The Positive Choice intervention achieved significant cessation of illicit drug use and unprotected sex at the group-level , and modest individual-level reductions in days of ongoing drug use and number of casual sex partners compared with the control group . Positive Choice , including Video Doctor counseling , is an efficacious and appropriate adjunct to risk-reduction efforts in outpatient setting s , and holds promise as a public health HIV intervention . Trial Registration Clinical trials.gov Objectives The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Isl and ers ( API ) than white homosexual men in the United States . The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate . HIV risk reduction is urgently needed in this population . Subjects and methods We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994 . Participants were r and omized into a single , 3-h skills training group or a wait-list control group . The intervention consisted of four components : ( 1 ) development of positive self-identity and social support , ( 2 ) safer sex education , ( 3 ) eroticizing safer sex , and ( 4 ) negotiating safer sex . Data were collected at baseline and 3 months after the intervention . Results Significant reductions in number of sexual partners were observed among all treatment subjects , regardless of ethnicity ( P= 0.003 ) . Treatment decreased the number of partners reported at 3-month follow-up by 46 % [ 95 % confidence interval ( CI ) , 28–77 ] . Chinese and Filipino men further benefited from the intervention : treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts ( odds ratio = 0.41 ; 95 % CI , 0.19–0.89 ; P= 0.024 ) . Conclusions We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API . Cities with significant API population s should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men Objectives : This paper review s the potential intervention approaches that have been used to prevent HIV through reducing risky sexual behaviours , summarizes the evidence on their effectiveness , primarily from trials , and discusses the way forward both in terms of research and programmes . Methods : An up date of a recent systematic review of HIV prevention interventions , focusing on trials that have included HIV as an outcome . Results : Five major intervention approaches have been used : community-wide sexual health education , adolescent sexual health interventions , interventions among groups most at risk , promotion of HIV testing and counseling , and interventions among HIV-positive individuals . The latter have often been underemphasized in programmes and research . Effective targeting of interventions to prevent HIV acquisition requires an underst and ing of HIV incidence by age and sex , whereas HIV prevalence patterns are critical for targeting interventions to reduce HIV transmission ( positive prevention ) . Unfortunately , none of the nine behavioural r and omized trials with HIV outcomes have shown a significant impact on HIV . Sometimes this has clearly been due to issues in trial design such as inadequate sample size or low coverage , but not always . Although more encouraging , trials with behavioural outcomes only can not be used to assume an impact on HIV due to the potential for misreporting and biases in reported sexual behaviour . Conclusion : Future research and programmes should place greater emphasis on interventions to reduce HIV transmission as well as acquisition , the sexual norms of the wider population , include a focus on concurrency , and on greatly increasing community acceptance and use of condoms Few behavioral interventions have been conducted to reduce high-risk sexual behavior among HIV-positive Men who have Sex with Men ( HIV+ MSM ) . Hence , we lack well-proven interventions for this population . Positive Connections is a r and omized controlled trial ( n = 675 HIV+ MSM ) comparing the effects of two sexual health seminars — for HIV+ MSM and all MSM — with a contrast prevention video arm . Baseline , 6- , 12- and 18-month follow-up surveys assessed psychosexual variables and frequency of serodiscordant unprotected anal intercourse ( SDUAI ) . At post-test , intentions to avoid transmission were significantly higher in the sexual health arms . However , SDUAI frequency decreased equally across arms . HIV+ MSM engaging in SDUAI at baseline were more likely to leave the study . Tailoring interventions to HIV+ MSM did not increase their effectiveness in this study . A sexual health approach appeared as effective as an untailored video-based HIV prevention intervention in reducing SDUAI among HIV+ MSM This controlled prospect i ve study assessed the effectiveness of a sexual health approach to HIV prevention for men who have sex with men ( MSM ) . Participants ( N = 422 Midwestern MSM ) were r and omly assigned to the intervention group , who participated in a 2-day comprehensive human sexuality seminar design ed to context ually address long-term risk factors and cofactors , or to the control group , who watched 3 hours of HIV prevention videos . Risk behavior during the preceding 3 months was measured at baseline , 3-month follow-up , and 12-month follow-up . Any unprotected anal intercourse outside a long-term seroconcordant relationship was the dependent variable . Of the total , 14%-24 % of the participants were considered at risk of acquiring or transmitting HIV . At the 12-month follow-up , the control reported a 29 % decrease in the use of condoms during anal intercourse ; the intervention group reported an 8 % increase ( t = 2.546 ; p = .015 ) . The sexual health seminars appear a promising new intervention at significantly reducing unprotected anal intercourse between men BACKGROUND Methamphetamine use has been associated with rising STI/HIV transmission rates , particularly among men who have sex with men ( MSM ) . Interventions which successfully reduce risk for HIV transmission among this population are a public health priority . This study examined the efficacy of a behavioral intervention for increasing safer sex behaviors in the context of ongoing methamphetamine use in a sample of HIV-positive , methamphetamine-using MSM . METHODS Three-hundred and forty-one participants from San Diego , CA were r and omly assigned to receive either a safer sex behavioral intervention ( EDGE ) or a time-equivalent diet- and -exercise attention-control condition . R and om effects regression analyses were used to evaluate change in safer sex behaviors over a 12-month period . RESULTS Participants in the EDGE intervention engaged in significantly more protected sex acts at the 8-month ( p=0.034 ) and 12-month assessment ( p=0.007 ) . By 12-months post-baseline , a greater percentage of protected sex acts was observed for EDGE ( 25.8 % ) vs. control participants ( 18.7 % ) ( p=0.038 ) . There was a significant time-by-intervention interaction ( p=0.018 ) for self-efficacy for condom use , suggesting that EDGE participants ' self-efficacy demonstrated a greater increase over time compared to control participants . CONCLUSIONS These results suggest that it is possible to reduce high risk sexual behaviors in the context of ongoing methamphetamine use among HIV-infected MSM CONTEXT High-risk sexual behavior is increasingly prevalent among men who have sex with men ( MSM ) and among men with a history of repeat testing for HIV . OBJECTIVES The study assessed whether one counseling intervention session focusing on self-justifications ( thoughts , attitudes , or beliefs that allow the participant to engage in high-risk sexual behaviors ) at most recent unprotected anal intercourse ( UAI ) is effective in reducing future high-risk behaviors among HIV-negative men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , controlled , counseling intervention trial was conducted at an anonymous testing site in San Francisco , California , between May 1997 and January 2000 . Participants were 248 MSM with a history of at least one previous negative HIV test result and self-reported UAI ( receptive or insertive ) in the previous 12 months with partners of unknown or discordant HIV status . Two intervention groups received st and ard HIV test counseling plus a cognitive-behavioral intervention , and two control groups received only st and ard HIV test counseling . Follow-up evaluation was at 6 and 12 months . MAIN OUTCOME MEASURE Number of episodes of UAI with non primary partners ( of unknown or discordant HIV status ) in the 90 days preceding the interview was measured via self-report during face-to-face interview . RESULTS A novel counseling intervention focusing on self-justifications significantly decreased the proportion of participants reporting UAI with non primary partners of unknown or discordant HIV status at 6 and 12 months ( from 66 % to 21 % at 6 months and to 26 % at 12 months , p = .002 ; p < .001 ) as compared with a control group when added to st and ard client-centered HIV counseling and testing . CONCLUSIONS A specific , single-session counseling intervention focusing on a reevaluation of a person 's self-justifications operant during a recent occasion of high-risk behavior may prove useful in decreasing individual risk behavior and thus limiting community-level HIV transmission This article reports pilot data from a newly developed disclosure intervention and associated measures specifically tailored for disclosure to casual sexual partners . Treatment consisted of a four-session , theoretically driven intervention focusing on the costs and benefits of disclosure . Using a r and omized control , crossover design 77 men were r and omized into one of three conditions ( wait-list control , facilitator only , and computer and facilitator ) . Results of the study suggest that facilitated administration of the pilot intervention was effective in reducing mean scores on the HIV disclosure behavior and attitude scales and that these reductions were both statistically and practically significant Men who have sex with men ( MSM ) , especially MSM of color , are disproportionately impacted by HIV/AIDS compared to heterosexuals and Caucasians . Nonetheless , fewer sexual and ethnic minorities participate in prevention interventions for people with HIV . We consider recruitment for Positive Connections , a r and omized controlled trial comparing unsafe sex prevention interventions primarily for HIV-positive ( HIV+ ) MSM in six US epicenters . One community-based organization ( CBO ) in each city recruited adult MSM , particularly men of color and HIV+ . Recruitment methods included on-line and print advertising , outreach events , health professionals , and social networks . Data on demographics , HIV status , and recruitment method were collected at registration . We tested for differences in registration proportions and attendance rates by recruitment strategy , stratified on race/ethnicity and serostatus . Of the 1,119 registrants , 889 attended the intervention . The sample comprised 41 % African American , 18 % Latino/Hispanic , and 77 % HIV+ . Friend referral was reported by the greatest proportion of registrants , particularly among African American ( 33 % ) and HIV+ men ( 25 % ) . Print advertising yielded the largest proportions of non-Hispanic white ( 27 % ) and HIV-negative registrants ( 25 % ) . Registrants recruited on-line were the least likely to attend ( 45 % versus 69 % average ) ; this effect was strongest among Latino/Hispanic ( 27 % attendance ) and non-Hispanic white men ( 36 % ) . Retention during the follow-up period did not differ by serostatus , race/ethnicity , or recruitment method . Differential attendance and retention according to recruitment strategy , serostatus , and racial/ethnic group can inform planning for intervention sample size goals BACKGROUND Community-level interventions may be helpful in population -focused HIV prevention . If members of population s at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers , decreases in risk behaviour may be possible . We assessed a community-level intervention to lower the risk of HIV infection , focusing on men patronising gay bars in eight small US cities . METHODS We used a r and omised community-level field design . Four cities received the intervention and four control cities did not . Participants were men from each city who went to gay bars . Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up . In the control cities , HIV educational material s were placed in the bars . In the intervention cities , we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation . FINDINGS Population -level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up , after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis , in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months ( baseline 1.68 occasions ; follow-up 0.59 : p = 0.04 ) and an increase in the mean percentage of occasions of anal intercourse protected by condoms ( baseline 44.7 % ; follow-up 66.8 % , p = 0.02 ) . Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports . INTERPRETATION Popular and well-liked members of a community who systematic ally endorse and recommend risk-reduction behaviour can influence the sexual-risk practice s of others in their social networks . Natural styles of communication , such as conversations , brought about population -level changes in risk behaviour OBJECTIVE Changes in immunologic status were evaluated in 25 HIV-infected men r and omly assigned to a 10-week stress management intervention or a wait-list control condition . METHOD The authors monitored changes in number of transitional naive T cells ( CD4(+)CD45RA(+)CD29(+ ) ) over 6 - 12 months after the completion of the intervention . RESULTS Men receiving stress management had higher CD4(+ ) CD45RA(+)CD29(+ ) cell counts at follow-up than did the control subjects . This difference was independent of initial number of naive T cells and HIV virus load . CONCLUSIONS Stress management is associated with immunologic reconstitution in HIV-positive gay men Objectives : To test the efficacy and acceptability of a single-session personalized cognitive counseling ( PCC ) intervention delivered by paraprofessionals during HIV voluntary counseling and testing . Methods : HIV-negative men who have sex with men ( MSM ; n = 336 ) were r and omly allocated to PCC or usual counseling ( UC ) between October 2002 and September 2004 . The primary outcome was the number of episodes of unprotected anal intercourse ( UAI ) with any non primary partner of nonconcordant HIV serostatus in the preceding 90 days , measured at baseline , 6 months , and 12 months . Impact was assessed as “ intent to treat ” by r and om-intercept Poisson regression analysis . Acceptability was assessed by a st and ardized client satisfaction survey . Results : Men receiving PCC and UC reported comparable levels of HIV nonconcordant UAI at baseline ( mean episodes : 4.2 vs. 4.8 , respectively ; P = 0.151 ) . UAI decreased by more than 60 % to 1.9 episodes at 6 months in the PCC arm ( P < 0.001 vs. baseline ) but was unchanged at 4.3 episodes for the UC arm ( P = 0.069 vs. baseline ) . At 6 months , men receiving PCC reported significantly less risk than those receiving UC ( P = 0.029 for difference to PCC ) . Risk reduction in the PCC arm was sustained from 6 to 12 months at 1.9 ( P = 0.181 ) , whereas risk significantly decreased in the UC arm to 2.2 during this interval ( P < 0.001 vs. 6 months ; P = 0.756 vs. PCC at 12 months ) . Significantly more PCC participants were “ very satisfied ” with the counseling experience ( 78.2 % ) versus UC participants ( 59.2 % ) ( P = 0.002 ) . Conclusions : Both interventions were effective in reducing high-risk sexual behavior among MSM repeat testers . PCC participants demonstrated significant behavioral change more swiftly and reported a more satisfying counseling experience than UC participants The authors examined the effectiveness of motivational interviewing ( MI ) on club drug use and risky sex in non-treatment-seeking men who have sex with men ( MSM ) . MSM ( N = 150 ) were assessed and r and omly assigned to 4 sessions of MI or an educational control intervention . Follow-up occurred at quarterly intervals for 1 year . Primary outcomes were days of any club drug use and number of unsafe sex acts . On average , club drug use declined during follow-up . A significant interaction effect showed that MI was associated with less club drug use during follow-up compared with education but only among participants with lower severity of drug dependence ( p < .02 ; small to medium effect size ) . MI did not result in a significant reduction in risky sex relative to education . The results support the use of MI targeting club drug use in at-risk or mildly dependent users not seeking treatment but not in more severely dependent users . MI does not appear effective in reducing risky sexual behavior in this population OBJECTIVES We describe the intervention tested in EXPLORE , an HIV prevention trial aim ed at men who have sex with men ( MSM ) , and test the empirical basis of the individually tailored intervention . METHODS Data on participants ' self-efficacy , communication skills , social norms , and enjoyment of unprotected anal intercourse were examined in relation to sexual risk . Combinations of these factors , together with alcohol use and noninjection drug use , were also examined . RESULTS The individual factors examined were associated with sexual risk behavior . The cohort was shown to be heterogeneous in regard to the presence of combinations of these risk-related factors . CONCLUSIONS Baseline data from the EXPLORE study support the efficacy of the individually tailored intervention used OBJECTIVE Primary care may be an effective venue for delivering behavioral interventions for sexual safety among HIV-positive men who have sex with men ( MSM ) ; however , few studies show efficacy for such an approach . We tested the efficacy of the Treatment Advocacy Program ( TAP ) , a 4-session , primary -care-based , individual counseling intervention led by HIV-positive MSM " peer advocates " in reducing unprotected sex with HIV-negative or unknown partners ( HIV transmission risk ) . METHOD We r and omized 313 HIV-positive MSM to TAP or st and ard care . HIV transmission risk was assessed at baseline , 6 months , and 12 months ( 251 participants completed all study waves ) . We conducted intent-to-treat analyses using general estimating equations to test the interaction of group ( TAP vs. st and ard care ) by follow-up period . RESULTS At study completion , TAP participants reported greater transmission risk reduction than did those receiving st and ard care , χ2(2 , N = 249 ) = 6.6 , p = .04 . Transmission risk among TAP participants decreased from 34 % at baseline to about 20 % at both 6 and 12 months : Transmission risk ranged from 23 % to 25 % among comparison participants . CONCLUSIONS TAP reduced transmission risk among HIV-positive MSM , although results are modest . Many participants and peer advocates commented favorably on the computer structure of the program . We feel that the key elements of TAP-computer-based and individually tailored session content , delivered by peers , in the primary care setting -warrant further exploration Objective : The primary objective of this study was to develop and test a highly interactive Internet-based HIV prevention intervention for men who have sex with men ( MSM ) . MSM remain the group at highest risk for HIV/AIDS in the United States and similar countries . As the Internet becomes popular for seeking sex , online interventions to reduce sexual risk are critical . Given previous studies , a secondary objective was to demonstrate that good retention is possible in online trials . Design : A r and omized controlled trial with 3-month , 6-month , 9-month , and 12-month follow-up design was employed . Methods : In 2008 , 650 participants were r and omized to an online , interactive sexual risk reduction intervention or to a waitlist null control . Results : Retention was 76–89 % over 12 months . At 3-month follow-up , results showed a 16 % reduction in reported unprotected anal intercourse risk among those in the treatment condition versus control [ 95 % confidence interval ( 95 % CI ) of rate ratio : 0.70–1.01 ] . No meaningful differences were observed at 12-month follow-up . Conclusion : Internet-based , persuasive computing programs hold promise as an effective new approach to HIV prevention for MSM , at least in the short term . Further , online trials can be conducted with acceptable retention provided strong retention protocol s are employed . Four directions for future research are identified Black men who have sex with men ( MSM ) in the United States experience disproportionately high rates of HIV and other sexually transmitted infections ( STIs ) ; however , the number of evidence -based interventions for Black MSM is limited . This study evaluated the efficacy of ManyMen , ManyVoices ( 3MV ) , a small-group HIV/STI prevention intervention developed by Black MSM-serving community-based organizations and a university-based HIV/STI prevention and training program . The study sample included 338 Black MSM of HIV-negative or unknown HIV serostatus residing in New York city . Participants were r and omly assigned to the 3MV intervention condition ( n = 164 ) or wait-list comparison condition ( n = 174 ) . Relative to comparison participants , 3MV participants reported significantly greater reductions in any unprotected anal intercourse with casual male partners ; a trend for consistent condom use during receptive anal intercourse with casual male partners ; and significantly greater reductions in the number of male sex partners and greater increases in HIV testing . This study is the first r and omized trial to demonstrate the efficacy of an HIV/STI prevention intervention for Black MSM OBJECTIVE Although many studies have documented patterns of emotional distress in persons with HIV disease , there have been few controlled evaluations of therapy outcomes with these individuals . This research evaluated the effects of brief cognitive-behavioral or social support group therapy with this population . METHOD Sixty-eight depressed men with HIV infection were r and omly assigned to one of three conditions : eight-session cognitive-behavioral groups , eight-session social support groups , or a comparison condition . Before and after intervention and at 3-month follow-up , all participants were individually assessed by using measures of symptoms of distress as well as substance use and sexual practice s. RESULTS Relative to the comparison group , both the cognitive-behavioral and social support group therapies produced reductions in depression , hostility , and somatization . The social support intervention also produced reductions in overall psychiatric symptoms and tended to reduce maladaptive interpersonal sensitivity , anxiety , and frequency of unprotected receptive anal intercourse , while the cognitive-behavioral intervention result ed in less frequent illicit drug use during the follow-up period . Tests for clinical significance of change particularly underscored benefits of the social support group intervention both at postintervention and at long-term follow-up . CONCLUSIONS Brief group therapy for depressed persons with HIV infection produced reductions in symptoms of distress . The two forms of therapy result ed in shared and unique improvements in functioning , although social support groups focused on emotional coping presented greater evidence of clinical ly significant change . As more persons contract HIV infection and live longer with HIV disease , further research is needed to evaluate outcomes of mental health services with these individuals We tested the impact of stress management training on sexual behavior and immune functioning in 64 gay men infected with human immunodeficiency virus ( HIV ) . Subjects r and omized to the stress management group met for eight two-hour sessions and one all day retreat to learn systematic relaxation , health behavior change , and stress management skills . Compared to those r and omized to a wait list control , treatment subjects reported significantly fewer sexual partners in the prior month at post-test ( 1.10 vs 2.29 for controls ) . There were no differences between groups in lymphocyte numbers and function Objective : To examine factors that explain the effect of a cognitive-behavioral intervention on reductions in HIV transmission risk among HIV-infected men who have sex with men ( MSM ) . Method : Of the 1910 HIV-infected MSM screened , 616 participants considered to be at risk of transmitting HIV were r and omized to a 15-session , individually delivered cognitive-behavioral intervention ( n = 301 ) or a wait-list control ( n = 315 ) . Results : Consistent with previous intent-to-treat findings , there was an overall reduction in transmission risk acts among MSM in both intervention and control arms , with significant intervention effects observed at the 5- , 10- , 15- , and 20-month assessment s ( risk ratios = 0.78 , 0.62 , 0.48 , and 0.38 , respectively ) . These intervention-related decreases in HIV transmission risk acts seemed to be partially due to sustained serosorting practice s. MSM in the intervention condition reported a significantly greater proportion of sexual partners who were HIV infected at the 5- and 10-month assessment s ( risk ratios = 1.14 and 1.18 ) . Conclusions : The Healthy Living Project , a cognitive-behavioral intervention , is efficacious in reducing transmission risk acts among MSM . This seems to have been due in large part to the fact that MSM in the intervention condition reported sustained serosorting practice BACKGROUND Methamphetamine-dependent gay and bisexual men ( GBM ) are at high risk for HIV transmission , largely due to drug-associated sexual risk behaviors . This project evaluated the efficacy of four behavioral drug abuse treatments for reducing methamphetamine use and sexual risk behaviors among this population . METHODS In this r and omized controlled trial , 162 methamphetamine-dependent ( SCID-verified ) GBM in Los Angeles County were r and omly assigned to one of four treatment conditions for 16 weeks : st and ard cognitive behavioral therapy ( CBT , n=40 ) , contingency management ( CM , n=42 ) , combined cognitive behavioral therapy and contingency management ( CBT+CM , n=40 ) , and a culturally tailored cognitive behavioral therapy ( GCBT , n=40 ) . Stimulant use was assessed thrice-weekly during treatment using urine drug screens ( 48 measures ) . Sexual risk behaviors were monitored monthly ( four measures ) . Follow-up assessment s were conducted at 6 ( 80.0 % ) and 12 months ( 79.9 % ) . RESULTS Statistically significant differences in retention ( F(3,158)=3.78 , p<.02 ) , in longest period of consecutive urine sample s negative for methamphetamine metabolites ( F(3,158)=11.80 , p<.001 ) , and in the Treatment Effectiveness Score were observed by condition during treatment ( F(3,158)=7.35 , p<.001 ) with post hoc analyses showing the CM and CBT+CM conditions to perform better than st and ard CBT . GEE modeling results showed GCBT significantly reduced unprotected receptive anal intercourse ( URAI ) during the first 4 weeks of treatment ( X2=6.75 , p<.01 ) . During treatment between-group differences disappeared at follow-up with overall reductions in outcomes sustained to 1-year . CONCLUSIONS Among high-risk methamphetamine-dependent GBM , drug abuse treatments produced significant reductions in methamphetamine use and sexual risk behaviors . Drug abuse treatments merit consideration as a primary HIV prevention strategy for this population This study evaluates two AIDS risk-reduction interventions targeted at homosexual and bisexual men . Participants were r and omized into two peer-led interventions : both involved a lecture on ' safer sex ' , and one provided a skills-training component during which men could discuss and rehearse the negotiation of safer sexual encounters . Follow-up data collection assessed self-reported changes in sexual behavior at 6 and 12 months . Skills training increased condom use for insertive anal intercourse . In sessions providing skills training , condom use increased , on average , by 44 % between pre-test and second follow-up compared with only 11 % on average in sessions which did not provide such training Objective To provide the first data which evaluates an HIV risk reduction intervention design ed to reduce HIV high-risk sexual behavior in African-American homosexual and bisexual men . Subjects Participants ( n = 318 ) were recruited from bars , bathhouses , and erotic bookstores , and through homosexual African-American organizations , street outreach , media advertisements , and personal referrals of individuals aware of the study . Methods Participants were r and omized into a single or triple session experimental group or a wait-list control group . Both experimental interventions included AIDS risk education , cognitive-behavioral self-management training , assertion training , and attempts to develop self-identity and social support . Data collection involved assessment s of self-reported changes in sexual behavior at 12− and 18-month follow-up . Results Participants in the triple session intervention greatly reduced their frequency of unprotected anal intercourse ( from 46 to 20 % ) at the 12-month follow-up evaluation and ( from 45 % to 20 % ) at the 18-month follow-up evaluation . However , levels of risky behavior for the control group remained constant ( from 26 to 23 % and from 24 to 18 % ) at 12− and 18-month follow-up evaluations , respectively . In addition , levels of risky behavior for the single session intervention decreased only slightly ( from 47 to 38 % and from 50 to 38 % ) at the 12− and 18-month follow-up evaluations , respectively . Conclusions Results were interpreted to demonstrate the superiority of a triple session over a single session intervention in reducing risky sexual behavior in this cohort This r and omized clinical trial ( N = 253 ) evaluated the efficacy of a theory-based intervention design ed to reduce both alcohol use and incidence of unprotected sexual behaviors among HIV-positive men who have sex with men with alcohol use disorders . An integrated , manualized intervention , using both individual counseling and peer group education/support , was compared with a control condition in which participants received re source referrals . The intervention was based on the transtheoretical model 's stages and processes of change , and motivational interviewing was used to enhance client readiness for change . Major findings include treatment effects for reduction in number of drinks per 30-day period , number of heavy drinking days per 30-day period , and number of days on which both heavy drinking and unprotected sex occurred . Practitioners employing this intervention may achieve enhanced client outcomes in reduction of both alcohol use and risky sexual behavior Background : Although several studies have characterized patterns and predictors of continued risky sexual behavior in HIV-infected rural persons , far less research has evaluated interventions to reduce risky sex in this group . This pilot r and omized clinical trial compared 2 brief telephone-administered interventions design ed to reduce continued risky sexual behaviors in HIV-infected rural persons . Methods : Participants were 79 HIV-infected rural persons who reported 1 or more occasions of unprotected anal , vaginal , or oral sex in the past 2 months . Participants were recruited through AIDS service organizations in rural areas of 27 states and assigned r and omly to either a 2-session , motivational interviewing plus skills-building intervention ( i.e. , integrated intervention ; n = 48 ) or a 2-session , skills-building only comparison intervention ( n = 31 ) . Participants completed self-report measures of sexual behaviors and factors related to risky sex at preintervention and 2-month follow-up . Results : Before enrolling into the intervention , 37 % of participants had 2 or more sexual partners in the past 2 months , 29 % had sex with 1 or more partners without knowing their partners ' HIV serostatus , and almost one-third of participants located sex partners in high-risk environments ( e.g. , public parks , roadside rest areas ) . A 2 × 2 repeated measures multivariate analyses of variance found that integrated intervention participants reported greater increases in risk-reduction motivation and greater increases in condom-protected vaginal and oral intercourse occasions at follow-up compared to skills-building only participants . Conclusions : Brief telephone-administered interventions that integrate motivational interviewing with skills-building show potential to reduce risky sexual behaviors in HIV-infected rural persons . Additional and large-scale evaluations of this intervention approach appear warranted While the HIV epidemic has disproportionately affected African American and Latino men who have sex with men ( MSM ) , few HIV prevention interventions have focused on African American and Latino men who have sex with both men and women ( MSMW ) . Even fewer interventions target HIV-positive African American and Latino MSM and MSMW with histories of childhood sexual abuse ( CSA ) , a population that may be vulnerable to high-risk sexual behaviors , having multiple sexual partners , and depression . The Men ’s Health Project , a small r and omized clinical trial , compared the effects of two 6-session interventions , the Sexual Health Intervention for Men ( S-HIM ) , guided by social learning theory and aim ed at decreasing high-risk sexual behaviors , number of sexual partners , and depressive symptoms , and a st and ard health promotion control ( SHP ) . A community sample of 137 HIV-positive gay and non-gay identifying African American and Latino MSM and MSMW with histories of CSA was recruited . Results were based on an “ intent to treat ” analyses of baseline to post , 3 and 6 month follow-ups . The sample as a whole reported reductions in sexual risk behaviors and number of sexual partners from baseline to post-test , and from the 3 to 6 month follow-ups , although the decrease in sexual risk behavior from baseline to post-test was significant only for S-HIM participants . No significant differences between conditions were reported for depressive symptoms , but the total sample reported a significant decrease at 6 months . These findings highlight the importance of addressing sexual decision-making and psychological adjustment for ethnic men , while being sensitive to CSA histories and sexual minority status , and suggest the need to develop additional strategies to heighten HIV risk reduction over time |
11,257 | 23,399,312 | In summary , existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation | Repetitive transcranial magnetic stimulation ( rTMS ) is a safe and effective treatment for major depression ( MD ) .
However , the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials .
Thus , we conducted a systematic review and meta- analysis of r and omized , double-blind and sham-controlled trials ( RCTs ) on high frequency ( HF- ) , low frequency ( LF- ) and bilateral rTMS for MD . | BACKGROUND Carefully design ed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation ( TMS ) in psychiatric disorders . A major method ological concern is the design of the " sham " control for TMS . An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment . Strategies employed so far include alterations in the position of the stimulating coil , but there has been little systematic study of their validity . In this study , we investigated the effects of different coil positions on cortical activation and scalp sensation . METHODS In nine normal subjects , single TMS pulses were administered at a range of intensities with a " figure eight " coil held in various positions over the left primary motor cortex . Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle . Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed . RESULTS None of the coil positions studied met the criteria for an ideal sham . Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex . CONCLUSIONS The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive " stimulation . " Further research is needed to develop the best sham condition for a range of applications BACKGROUND Studies of repetitive transcranial magnetic stimulation ( rTMS ) in depression have mostly involved once-daily treatment , with positive but modest clinical results . This study tested the efficacy and safety of twice-daily rTMS over 2 weeks . METHOD Thirty-eight depressed subjects enrolled in a double-blind , sham-controlled trial of twice-daily rTMS ( left prefrontal cortex , 10 Hz , 110 % intensity , 1500 stimuli per session ) over 2 weeks . Mood and neuropsychological functioning were assessed weekly by blind raters , using the Montgomery-Asberg Depression Rating Scale ( MADRS ) as the primary outcome measure , plus the Hamilton Rating Scale for Depression ( HRSD ) and self-report measures . After the blind period , 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS . RESULTS Subjects were moderately treatment resistant . Active treatment result ed in significantly greater improvement than sham over the 2-week blind period on one outcome measure only ( MADRS p<0.05 ) . Subjects showed further improvement over the 6 weeks of active rTMS . Neuropsychological test scores did not change significantly . CONCLUSIONS rTMS given twice daily was effective and safe , with no adverse neuropsychological effects OBJECTIVE There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation ( rTMS ) as a neuromodulatory treatment . However , there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects , which may be particularly strong in psychiatric patients . This is due to the fact that existing sham rTMS procedures are less than optimal . A new placebo tool is introduced here , called real electro-magnetic placebo ( REMP ) device , which can simulate the scalp sensation induced by the real TMS , while leaving both the visual impact and acoustic sensation of real TMS unaltered . METHODS Physical , neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures ( at different intensities ) were tested in subjects who were expert or naïve of TMS . Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures , namely the commercially available Magstim sham coil and tilting the real coil by 90 degrees . RESULTS The REMP device , besides producing scalp sensations similar to the real TMS , attenuated the TMS-induced electric field ( as measured by a dipole probe ) to a biologically inactive level . Behaviourally , neither expert nor naïve TMS subjects identified the " coil at 90 degrees " or the " Magstim sham coil " as a real TMS intervention , whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real . CONCLUSIONS The " goodness of sham " of the REMP device is demonstrated by physical , neurophysiological , and behavioural results . SIGNIFICANCE Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS , as in case of patients undergoing a clinical rTMS trial OBJECTIVE High-frequency left-side repetitive transcranial magnetic stimulation ( rTMS ) and low-frequency stimulation to the right prefrontal cortex have both been shown to have antidepressant effects , but doubts remain about the magnitude of previously demonstrated treatment effects . The authors evaluated sequentially combined high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex for treatment-resistant depression . METHOD The authors conducted a 6-week double-blind , r and omized , sham-controlled trial in 50 patients with treatment-resistant depression . Three trains of low-frequency rTMS to the right prefrontal cortex of 140 seconds ' duration at 1 Hz were applied daily , followed immediately by 15 trains of 5 seconds ' duration of high-frequency left-side rTMS at 10 Hz . Sham stimulation was applied with the coil angled at 45 degrees from the scalp , resting on the side of one wing of the coil . The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale . RESULTS There was a significantly greater response to active than sham stimulation at 2 weeks and across the full duration of the study . A significant proportion of the study group receiving active treatment met response ( 11 of 25 [ 44 % ] ) or remission ( nine of 25 [ 36 % ] ) criteria by study end compared to the sham stimulation group ( two of 25 [ 8 % ] and none of 25 respectively ) . CONCLUSIONS Sequentially applying both high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex , has substantial treatment efficacy in patients with treatment-resistant major depression . The treatment response accumulates to a clinical ly meaningful level over 4 to 6 weeks of active treatment BACKGROUND Repetitive transcranial magnetic stimulation ( TMS ) as a treatment for depression has shown statistically significant effects , but the clinical significance of these effects has been question ed . METHODS Patients with medication-resistant depression were r and omized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110 % the estimated prefrontal cortex threshold . Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains . The primary end point was treatment response defined as a > or=50 % decrease in Hamilton Depression Rating Scale ( HDRS ) score at both 1 and 2 weeks following the final repetitive TMS treatment . Remission was defined as a HDRS score < 8 . RESULTS The response rate for the TMS group was 30.6 % ( 11/35 ) , significantly ( p = .008 ) greater than the 6.1 % ( 2/33 ) rate in the sham group . The remission rate for the TMS group was 20 % ( 7/35 ) , significantly ( p = .033 ) greater than the 3 % ( 1/33 ) rate in the sham group . The HDRS scores showed a significantly ( p < .002 ) greater decrease over time in the TMS group compared with the sham group . CONCLUSIONS Transcranial magnetic stimulation can produce statistically and clinical ly significant antidepressant effects in patients with medication-resistant major depression CONTEXT Daily left prefrontal repetitive transcranial magnetic stimulation ( rTMS ) has been studied as a potential treatment for depression , but previous work had mixed outcomes and did not adequately mask sham conditions . OBJECTIVE To test whether daily left prefrontal rTMS safely and effectively treats major depressive disorder . DESIGN Prospect i ve , multisite , r and omized , active sham-controlled ( 1:1 r and omization ) , duration -adaptive design with 3 weeks of daily weekday treatment ( fixed-dose phase ) followed by continued blinded treatment for up to another 3 weeks in improvers . SETTING Four US university hospital clinics . PATIENTS Approximately 860 out patients were screened , yielding 199 antidepressant drug-free patients with unipolar nonpsychotic major depressive disorder . INTERVENTION We delivered rTMS to the left prefrontal cortex at 120 % motor threshold ( 10 Hz , 4-second train duration , and 26-second intertrain interval ) for 37.5 minutes ( 3000 pulses per session ) using a figure-eight solid-core coil . Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations . MAIN OUTCOME MEASURE In the intention-to-treat sample ( n = 190 ) , remission rates were compared for the 2 treatment arms using logistic regression and controlling for site , treatment resistance , age , and duration of the current depressive episode . RESULTS Patients , treaters , and raters were effectively masked . Minimal adverse effects did not differ by treatment arm , with an 88 % retention rate ( 90 % sham and 86 % active ) . Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters ( 14.1 % active rTMS and 5.1 % sham ) ( P = .02 ) . The odds of attaining remission were 4.2 times greater with active rTMS than with sham ( 95 % confidence interval , 1.32 - 13.24 ) . The number needed to treat was 12 . Most remitters had low antidepressant treatment resistance . Almost 30 % of patients remitted in the open-label follow-up ( 30.2 % originally active and 29.6 % sham ) . CONCLUSION Daily left prefrontal rTMS as monotherapy produced statistically significant and clinical ly meaningful antidepressant therapeutic effects greater than sham . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00149838 Abstract Objectives . High frequency left-sided ( HFL ) and low frequency right-sided ( LFR ) unilateral repetitive transcranial magnetic stimulation ( rTMS ) are efficacious in treatment-resistant major depression ( TRD ) . Similar benefit has been suggested for sequential bilateral rTMS ( LFR then HFL ) . There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS . Therefore , this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD . Methods . Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital . Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale ( HDRS ) greater than 21 were r and omized to receive unilateral , bilateral , or sham rTMS . The rates of remission were compared among the three treatment groups . Results . The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy ( ECT ) during the current episode . The remission rate was significantly higher in the bilateral group than the sham group . The remission rate in the unilateral group did not differ from either group . Conclusion . These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation ( rTMS ) treatment trials is a central issue . On the one h and , the ideal sham condition should not have a real stimulation effect ; on the other h and , it should not be recognized as sham by patients , particularly when considering that real stimulation conditions come along with rTMS specific side effects . Within the course of a multi-centre trial assessing the antidepressant effects of rTMS , patients were r and omized to sham or real stimulation , in both cases using a st and ard stimulation coil . In one centre , patients ( n=33 ) were asked about their impression whether they received the sham or the real treatment , and if they would recommend the treatment to others . 29 patients returned the question naires and were included into the analysis . From 15 subjects with real stimulation , 11 suggested to have obtained real , and 4 to have obtained sham . From 14 sham stimulated subjects , 9 suggested to have obtained the real condition and 5 to have been sham stimulated . This difference was not significant ( p=0.60 , chi square test ) . In addition , the major part of patients in both stimulation conditions would recommend rTMS to others . In both conditions , real and sham , the majority of subjects believed to have obtained the real condition . This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition . The results imply the feasibility of a valid sham condition with a " real " coil OBJECTIVES Repetitive transcranial magnetic stimulation ( rTMS ) has been shown to improve depressive symptoms . We design ed and carried out the following left prefrontal rTMS study to determine the safety , feasibility , and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder ( BPAD ) . METHODS We recruited and enrolled 23 depressed BPAD patients ( 12 BPI depressed state , nine BPII depressed state , two BPI mixed state ) . Patients were r and omly assigned to receive either daily left prefrontal rTMS ( 5 Hz , 110 % motor threshold , 8 sec on , 22 sec off , over 20 min ) or placebo each weekday morning for 2 weeks . Motor threshold and subjective rating scales were obtained daily , and blinded Hamilton Rating Scale for Depression ( HRSD ) and Young Mania Rating Scales ( YMRS ) were obtained weekly . RESULTS Stimulation was well tolerated with no significant adverse events and with no induction of mania . We failed to find a statistically significant difference between the two groups in the number of antidepressant responders ( > 50 % decline in HRSD or HRSD < 10 - 4 active and 4 sham ) or the mean HRSD change from baseline over the 2 weeks ( t = -0.22 , p = 0.83 ) . Active rTMS , compared with sham rTMS , produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t = 1.58 , p = 0.13 ) . The motor threshold did not significantly change after 2 weeks of active treatment ( t = 1.11 , p = 0.28 ) . CONCLUSIONS Daily left prefrontal rTMS appears safe in depressed BPAD subjects , and the risk of inducing mania in BPAD subjects on medications is small . We failed to find statistically significant TMS clinical antidepressant effects greater than sham . Further studies are needed to fully investigate the potential role , if any , of TMS in BPAD depression Blinding , or “ masking , ” is a crucial method for reducing bias in r and omized clinical trials . In this paper , we review important method ological aspects of blinding , emphasizing terminology , reporting , bias mechanisms , empirical evidence , and the risk of unblinding . Theoretical considerations and empirical analyses support the blinding of patients , health‐care providers , and outcome assessors as to the trial intervention to which patients have been allocated . We encourage extensive pretrial testing of blinding procedures and explicit reporting of who was in the blinded condition and the methods used to ensure blinding BACKGROUND Effectiveness of repetitive transcranial magnetic stimulation ( rTMS ) for major depression is unclear . The authors performed a r and omized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up . METHOD Fifty-nine patients with major depression were r and omly assigned to a 10-day course of either real ( n=29 ) or sham ( n=30 ) rTMS of the left dorsolateral prefrontal cortex ( DLPFC ) . Primary outcome measures were the 17-item Hamilton Depression Rating Scale ( HAMD ) and proportions of patients meeting criteria for response ( 50 % reduction in HAMD ) and remission ( HAMD8 ) after treatment . Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales , Brief Psychiatric Rating Scale ( BPRS ) score , and both self-reported and observer-rated cognitive changes . Patients had 6-week and 4-month follow-ups . RESULTS Overall , Hamilton Depression Rating Scale ( HAMD ) scores were modestly reduced in both groups but with no significant groupxtime interaction ( p=0.09 ) or group main effect ( p=0.85 ) ; the mean difference in HAMD change scores was -0.3 ( 95 % CI -3.4 to 2.8 ) . At end-of-treatment time-point , 32 % of the real group were responders compared with 10 % of the sham group ( p=0.06 ) ; 25 % of the real group met the remission criterion compared with 10 % of the sham group ( p=0.2 ) ; the mean difference in HAMD change scores was 2.9 ( 95 % CI -0.7 to 6.5 ) . There were no significant differences between the two groups on any secondary outcome measures . Blinding was difficult to maintain for both patients and raters . CONCLUSIONS Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression |
11,258 | 19,681,737 | 10 studies investigated criterion-related validity and provided evidence that while ultrasound may be a valid measure of trunk muscle size , the validity of ultrasound to quantify muscle activation is context -dependent , depending on the muscle involved , the contraction strategy utilised , and the intensity of muscle contraction .
It is valid to use rehabilitative ultrasound imaging to measure trunk muscle size and activation during most isometric sub-maximal contractions .
Ultrasound measures appear sensitive to both positive and negative change | QUESTIONS Is rehabilitative ultrasound imaging a valid measure of trunk muscle size and activation ?
Are rehabilitative ultrasound imaging measures sensitive to change ? | Study Design . A r and omized clinical trial with 1-year and 3-year telephone question naire follow-ups . Objective . To report a specific exercise intervention ’s long-term effects on recurrence rates in acute , first-episode low back pain patients . Summary of Background Data . The pain and disability associated with an initial episode of acute low back pain ( LBP ) is known to resolve spontaneously in the short-term in the majority of cases . However , the recurrence rate is high , and recurrent disabling episodes remain one of the most costly problems in LBP . A deficit in the multifidus muscle has been identified in acute LBP patients , and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity . Any relation between this deficit and recurrence rate was investigated in the long-term . Methods . Thirty-nine patients with acute , first-episode LBP were medically managed and r and omly allocated to either a control group or specific exercise group . Medical management included advice and use of medications . Intervention consisted of exercises aim ed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle . One year and three years after treatment , telephone question naires were conducted with patients . Results . Question naire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group . One year after treatment , specific exercise group recurrence was 30 % , and control group recurrence was 84 % ( P < 0.001 ) . Two to three years after treatment , specific exercise group recurrence was 35 % , and control group recurrence was 75 % ( P < 0.01 ) . Conclusion . Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone Study Design . A prospect i ve study of multifidus images . Objective . To compare the change of the cross-sectional area ( CSA ) of multifidus in subjects with and without chronic low back pain ( LBP ) at different postures . Summary of Background Data . Ultrasound imaging was shown to be useful in assessing acute LBP patients at rest only . Methods and Measures . Thirty-five male adults participated , including 19 normal and 16 chronic LBP patients . The CSAs of multifidus were assessed on ultrasound images acquired on both sides of the L4 and L5 levels with the subjects in prone lying , upright st and ing , and 25 ° and 45 ° forward stooping . Results . In the control group , the CSA of multifidus increased from prone lying to upright st and ing and then gradually decreased from 25 ° to 45 ° forward stooping . However , a reverse pattern of the CSA changes was identified in patients with chronic LBP . Conclusion . Multifidus contracts maximally at upright st and ing in the normal group , while maximum contraction of the muscle occurs at 25 ° forward stooping in the patient group . The role of multifidus may be altered in the stabilization of the lumbar spine of chronic LBP patients . Assessment of the change in muscle size reacting to different postures is found to be helpful OBJECTIVE To compare trunk muscle coordination in people with and without low back pain with varying speeds of limb movement . STUDY DESIGN Abdominal and back extensor muscle activity in association with upper limb movement was compared among three speeds of movement and between people with and without low back pain . PARTICIPANTS Fourteen subjects with a history of recurrent low back pain and a group of age- and sex-matched control subjects . MEASURES The onsets of electromyographic activity of the trunk and limb muscles , frequency of trunk muscle responses , and angular velocity of arm movements . RESULTS Early activation of transversus abdominis ( TrA ) and obliquus internus abdominis ( OI ) occurred in the majority of trials , with movement at both the fast and intermediate speeds for the control group . In contrast , subjects with low back pain failed to recruit TrA or OI in advance of limb movement with fast movement , and no activity of the abdominal muscles was recorded in the majority of intermediate speed trials . There was no difference between groups for slow movement . CONCLUSION The results indicate that the mechanism of preparatory spinal control is altered in people with lower back pain for movement at a variety of speeds Ultrasonography has recently been proposed for assessing changes in thickness and motion of the diaphragm during contraction in humans . Data on ultrasound assessment of abdominal muscles in humans are scarce . We therefore investigated the changes in thickness and the relevant mechanical effects of abdominal muscles using this technique during respiratory manoeuvres in normal subjects . We evaluated the thickness of the abdominal muscle layers in six normal male subjects ( aged 26 - 36 yrs ) using a 7.5 MHz B-mode ultrasound transducer . Gastric ( Pg ) and mouth pressures , muscle thickness of external oblique ( EO ) , internal oblique ( IO ) , transversus abdominis ( TA ) and rectus abdominis ( RA ) were assessed at functional residual capacity ( FRC ) , residual volume ( RV ) , total lung capacity ( TLC ) , during progressive ( PEEs ) and maximal expiratory efforts ( MEEs ) against a closed airway and during homolateral ( HTR ) and contralateral ( CTR ) trunk rotation . Abdominal muscle thickness was found to be reproducible ( coefficient of variation and two-way analysis of variance ) . Compared to FRC , the thickness of IO , TA and RA significantly increased at RV and during MEEs , whereas EO remained unchanged ; at TLC , the thickness of IO and TA significantly decreased . During PEEs , a significant relationship between increase in Pg and TA thickness was observed in all subjects , the thickness of the other abdominal muscles being inconsistently related to Pg . Finally , a significant increase in the thickness of IO and EO was found during HTR and CTR , respectively . We conclude that during maximal expiratory manoeuvres , transversus abdominis , internal oblique and rectus abdominis thickened similarly . Transversus abdominis seems to be the major contributor in generating abdominal expiratory pressure during progressive expiratory efforts . External oblique seems to be preferentially involved during trunk rotation . These results suggest the possible value of study ing the abdominal muscles by ultrasonography in various respiratory disorders BACKGROUND AND PURPOSE Low abdominal hollowing in four-point kneeling is used clinical ly to test and rehabilitate transversus abdominis ( TrA ) but many people find this exercise difficult to perform . Contracting pelvic floor muscles ( PF ) during low abdominal hollowing may facilitate contraction of TrA. Thickness increase in the abdominal muscles during low abdominal hollowing has been measured with real-time ultrasound scanning and may indicate muscle contraction . The present study investigated the effect of instructing PF contraction on TrA thickness increase during low abdominal hollowing . METHOD Twelve females and eight males with no reported pelvic floor dysfunction or low back pain in the last two years were taught low abdominal hollowing in four-point kneeling . Subjects performed low abdominal hollowing with and without instruction to contract PF in r and om order . Transversus abdominis , obliquus internus ( OI ) and obliquus externus ( OE ) thickness were measured with ultrasound scanning at rest and during both tests . RESULTS Mean increase in TrA thickness during low abdominal hollowing was 49.71 % ( SD 26.76 % ) , during low abdominal hollowing with PF it was 65.81 % ( SD 23.53 % ) . Paired Student 's t-tests indicated a significant difference between tests ( p = 0.015 ) . There were no significant differences between tests for OE or OI thickness increase . CONCLUSIONS Instructing healthy subjects to co-contract PF results in greater increase in TrA thickness during low abdominal hollowing in four-point kneeling . This may indicate greater contraction of TrA and thus be useful for clinicians training TrA. Further research could investigate the validity of change of thickness as a measure of abdominal muscle contraction , investigate the effect of instructing PF co-contraction on TrA in patients with low back pain and measure PF and TrA activity simultaneously This cross-sectional , prospect i ve study aim ed to produce normal reference data for measurements of the lumbar multifidus muscle . A total of 120 subjects , 68 females ( aged 20 - 64 years ) and 52 males ( 20 - 69 years ) were studied . Bilateral transverse ultrasound images were made of multifidus at the fourth and fifth lumbar vertebrae ( L4 & L5 ) . Cross-sectional area ( CSA , cm(2 ) ) and linear dimensions ( AP , anteroposterior ; Lat , lateral ) were measured and the latter expressed as a ratio ( AP/Lat ) to reflect shape . Relationships between CSA and anthropometric measures were examined . Multifidus CSA was larger in males ( P<0.001 ) and age had no effect . The CSA was larger at L5 than L4 ( P<0.001 ) and highly correlated between the two levels ( males r=0.82 , females 0.80 ) . Differences in muscle shape were observed for gender , age and vertebral level . Between-side symmetry was high for size but not shape ( CSA < 10 % difference ) . Linear measurements multiplied ( APxLat ) correlated highly with CSA ( all groups r0.94 , P<0.0001 ) . The AP dimension was also acceptably predictive of CSA at L4 ( r0.79 ) . There were no clinical ly useful correlations between CSA and anthropometric measures . These findings provide normal references ranges for objective assessment of lumbar multifidus . This paper also addresses specific practical issues when scanning multifidus 1 . Human gastrocnemius medialis architecture was analysed in vivo , by ultrasonography , as a function of joint angle at rest and during voluntary isometric contractions up to the maximum force ( MCV ) . maximum force ( MVC ) . 2 . At rest , as ankle joint angle increased from 90 to 150 deg , pennation increased from 15.8 to 27.7 deg , fibre length decreased from 57.0 to 34.0 mm and the physiological cross-sectional area ( PCSA ) increased from 42.1 to 63.5 cm2 . 3 . From rest to MVC , at a fixed ankle joint angle of 110 deg , pennation angle increased from 15.5 to 33.6 deg and fibre length decreased from 50.8 to 32.9 mm , with no significant change in the distance between the aponeuroses . As a result of these changes the PCSA increased by 34.8 % . 4 . Measurements of pennation angle , fibre length and distance between the aponeuroses of the gastrocnemius medialis were also performed by ultrasound on a cadaver leg and found to be in good agreement with direct anatomical measurements . 5 . It is concluded that human gastrocnemius medialis architecture is significantly affected both by changes of joint angle at rest and by isometric contraction intensity . The remarkable shortening observed during isometric contraction suggests that , at rest , the gastrocnemius muscle and tendon are considerably slack . The extrapolation of muscle architectural data obtained from cadavers to in vivo conditions should be made only for matching muscle lengths Study Design . Intrasubject controls with r and omized intervention order . Objective . To quantify the immediate change in posteroanterior ( PA ) spinal stiffness produced by different combinations of trunk muscle contraction . Summary of Background Data . The abdominal hollow and the abdominal brace are 2 different combinations of trunk muscle contractions that are commonly prescribed to increase spinal stability . Unfortunately , the immediate effect of these different contractions on spinal stiffness ( one indicator of spinal stability ) has not yet been quantified directly . Methods . Twenty-eight asymptomatic subjects were taught abdominal hollow and brace contractions then performed them in a r and omized order framed by periods of rest . Surface electromyography and B-mode ultrasound confirmed that all contractions were performed appropriately . During each test condition ( hollow , brace , and rest ) , a noninvasive indentation technique was used to quantify PA spinal stiffness . A repeated measures analysis of variance was used to assess the significance of changes in the PA spinal stiffness between test conditions . Results . Both the abdominal hollow and abdominal brace contractions increased PA spinal stiffness significantly when compared with the rest condition ( P < 0.001 ) . When the abdominal hollow and brace contractions were compared with each other , the abdominal brace contraction produced significantly greater PA spinal stiffness ( P < 0.05 ) . Conclusion . In asymptomatic subjects , the abdominal brace contraction provided an immediate PA stiffening effect that was significantly greater in magnitude when compared with conditions of rest and abdominal hollowing . These findings may allow clinicians to better match commonly prescribed contraction-based interventions with specific patient needs . Future work is required to assess the long-term effect of repeated abdominal brace and hollow contractions on PA spinal stiffness and low back pain Rehabilitative ultrasound imaging ( RUSI ) is considered a valid method to measure muscle activation in key spinal muscles in asymptomatic subjects . Research measuring muscle activation with RUSI in painful subjects is limited . The aim of this study was to determine if changes in muscle activation from experimentally induced pain can be measured by RUSI . Six male subjects performed tasks known to activate the transverse abdominis ( TrA ) and lumbar multifidus ( LM ) while RUSI measurements of muscle thickness were obtained during control and hypertonic saline conditions . The abdominal draw-in maneuver was used to volitionally activate the TrA and a series of upper extremity lifting tasks were used to automatically activate the LM . Pain was induced by injecting 5 % hypertonic saline into the longissimus muscle adjacent to the LM at the L4 level . The percent change in muscle thickness from rest to contraction represented muscle activation . Activation was significantly less ( p<0.01 ) during the painful condition on 4 of the 5 tasks performed for the LM and on the task performed for the TrA. These results indicate that RUSI can be used to measure pain-related changes in deep trunk muscle activation . Future research should include a larger sample size and women OBJECTIVE To investigate the relationship between changes in thickness and EMG activity in the transversus abdominis muscle of healthy subjects and the reliability of ultrasound measurements using different modes and transducers . DESIGN Convenience sampling . BACKGROUND Chronic low back pain is associated with transversus abdominis dysfunction but EMG studies of this muscle are restricted to invasive techniques . Since the thickness of transversus abdominis changes with activity , such changes measured from ultrasound images might provide insight into this muscle 's function non-invasively . In addition , little is known about the comparability of ultrasound measurements from different modes and transducers , nor the reliability of transversus abdominis measurements . METHODS In 9 healthy subjects ( aged 29 - 52 years , four male ) transversus abdominis was studied at rest and during activity ( 5 - 80 % max ) with simultaneous EMG and ultrasound ( M mode , 5 MHz curvilinear transducer ) measurements . Intra-rater reliability for thickness measurements was studied on 13 subjects using 7.5 MHz linear and 5 MHz curvilinear transducers in B and M modes . RESULTS Muscle thickness changes correlated well with EMG activity ( P < 0.001 , R2 = 0.87 ) and there were no significant differences between subjects ( P > 0.05 ) . Using 7.5 MHz head , the ICC for B mode was 0.989 and for M mode was 0.981 for between days reliability . The ICC for between transducer reliability was 0.817 . CONCLUSIONS Changes in thickness of transversus abdominis can be used to indicate changes in the electrical activity in this muscle . RELEVANCE Ultrasound scanning can be used in the clinical setting to provide objective information about transversus abdominis function STUDY DESIGN R and omized controlled trial . OBJECTIVE To determine if the provision of visual biofeedback using real-time ultrasound imaging enhances the ability to activate the multifidus muscle . BACKGROUND Increasingly clinicians are using real-time ultrasound as a form of biofeedback when re-educating muscle activation . The effectiveness of this form of biofeedback for the multifidus muscle has not been reported . METHODS AND MEASURES Healthy subjects were r and omly divided into groups that received different forms of biofeedback . All subjects received clinical instruction on how to activate the multifidus muscle isometrically prior to testing and verbal feedback regarding the amount of multifidus contraction , which occurred during 10 repetitions ( acquisition phase ) . In addition , 1 group received visual biofeedback ( watched the multifidus muscle contract ) using real-time ultrasound imaging . All subjects were reassessed a week later ( retention phase ) . RESULTS Subjects from both groups improved their voluntary contraction of the multifidus muscle in the acquisition phase ( P<.001 ) and the ability to recruit the multifidus muscle differed between groups ( P<.05 ) , with subjects in the group that received visual ultrasound biofeedback achieving greater improvements . In addition , the group that received visual ultrasound biofeedback retained their improvement in performance from week 1 to week 2 ( P>.90 ) , whereas the performance of the other group decreased ( P<.05 ) . CONCLUSION Real-time ultrasound imaging can be used to provide visual biofeedback and improve performance and retention in the ability to activate the multifidus muscle in healthy subjects BACKGROUND Delayed anticipatory muscle activity response in deep abdominal and back muscles has been observed in patients with low back pain , indicative of a pathological condition . Muscle activity onset is traditionally recorded by intramuscular electromyography , but there is a need for a non-invasive and less cumbersome recording method in large clinical studies . An experimental study was carried out to explore whether high-frame rate m-mode ultrasound could measure anticipatory muscle responses ( " onset " ) in the lumbar multifidus muscle reliably and comparably accurate to intramuscular electromyography . METHODS Muscle activity onset was recorded by ultrasound m-mode and intramuscular electromyography . Ultrasound m-mode with a temporal resolution of 500 s(-1 ) ( frames per second ) was used to record rapid movements caused by muscle deformations in multifidus . In ultrasound m-mode , the frequency of each echo signal from 0.15 mm incremental depth levels is analysed . The frequency of these signals is proportional to the velocity of the interrogated tissue . The mean amplitude of the high-pass filtered echo signals within a pre-set depth range was plotted against time , and used to indicate onset . The results were compared to muscle activity onset in the multifidus recorded simultaneously by intramuscular electromyography . FINDINGS High inter-rater agreement was found for visual determination of onset within both methods . The smallest detectable difference was 21 and 24 ms for electromyography and the ultrasound methods , respectively . The ultrasound m-mode method recorded muscle activity onset in the deep multifidus on average 16 ms ( SD 21 ) later than intramuscular electromyography . For single trials , large variation and thus unacceptable method agreement was found . INTERPRETATION Ultrasound m-mode imaging at high time resolution can detect onset of muscle activity comparably accurate to intramuscular electromyography , but with a small systematic delay that should be corrected for in onset determination by m-mode ultrasound . Regardless of recording method , onset estimates should be based on averaged values of repeated trials . Further studies are needed to explore the applicability of the ultrasound method in clinical setting Study Design A clinical study was conducted on 39 patients with acute , first‐episode , unilateral low back pain and unilateral , segmental inhibition of the multifidus muscle . Patients were allocated r and omly to a control or treatment group . Objectives To document the natural course of lumbar multifidus recovery and to evaluate the effectiveness of specific , localized , exercise therapy on muscle recovery . Summary of Background Data Acute low back pain usually resolves spontaneously , but the recurrence rate is high . Inhibition of multifidus occurs with acute , first‐episode , low back pain , and pathologic changes in this muscle have been linked with poor outcome and recurrence of symptoms . Methods Patients in group 1 received medical treatment only . Patients in group 2 received medical treatment and specific , localized , exercise therapy . Outcome measures for both groups included 4 weekly assessment s of pain , disability , range of motion , and size of the multifidus cross‐sectional area . Independent examiners were blinded to group allocation . Patients were reassessed at a 10‐week follow‐up examination . Results Multifidus muscle recovery was not spontaneous on remission of painful symptoms in patients in group 1 . Muscle recovery was more rapid and more complete in patients in group 2 who received exercise therapy ( P = 0.0001 ) . Other outcome measurements were similar for the two groups at the 4‐week examination . Although they resumed normal levels of activity , patients in group 1 still had decreased multifidus muscle size at the 10‐week follow‐up examination . Conclusions Multifidus muscle recovery is not spontaneous on remission of painful symptoms . Lack of localized , muscle support may be one reason for the high recurrence rate of low back pain following the initial episode BACKGROUND There is little information about the relationship between the changes of hemodynamics and the morphologic changes of the erector spinae muscle . METHODS Fifty healthy male volunteers participated . Ultrasonography was used to measure muscle thickness , and near-infrared spectroscopy was used to measure tissue blood volume and its oxygenation in the erector spinae muscle at L3 in six different relaxed trunk postures ( flexed 20 degrees , flexed 40 degrees , flexed maximum , neutral posture , extended 20 degrees , and extended maximum of the lumbar spine ) . We also evaluated the reproducibility of the near-infrared spectroscopy measurements . FINDINGS Near-infrared spectroscopy gave highly reproducible measurements . The thickness of the erector spinae muscle and the total and oxygenated hemoglobin were simultaneously increased during relaxed extension and decreased during relaxed flexion . Changes in the thickness of the erector spinae muscle with various lumbar curvature were similar in pattern to the changes in tissue blood volume and its oxygenation . INTERPRETATION The erector spinae muscles ' thickness , tissue blood volume , and its oxygenation are simultaneously increased during relaxed extension and decreased during relaxed flexion , as demonstrated by non-invasive near-infrared spectroscopy and ultrasonography . These findings might afford a better underst and ing of the pathomechanics of posture-related back symptoms . RELEVANCE The erector spinae muscles ' thickness , tissue blood volume , and its oxygenation are simultaneously increased during relaxed extension and decreased during relaxed flexion , as shown by non-invasive near-infrared spectroscopy and ultrasonography . Changes in hemodynamics and morphology of the erector spinae muscles in asymptomatic subjects are given for further research on the pathomechanism of back pain RATIONALE AND OBJECTIVES Quality Assessment of Diagnostic Accuracy Studies ( QUADAS ) is a new tool to measure the method ological quality of diagnostic accuracy studies in systematic review s. We used data from a systematic review of magnetic resonance spectroscopy ( MRS ) in the characterization of suspected brain tumors to provide a preliminary evaluation of the inter-rater reliability of QUADAS . MATERIAL S AND METHODS A structured literature search identified 19 diagnostic accuracy studies . These publications were distributed r and omly to primary and secondary review ers for dual independent assessment . Review ers recorded method ological quality by using QUADAS on a custom- design ed spreadsheet . We calculated correlation , percentage of agreement , and kappa statistic to assess inter-rater reliability . RESULTS Most studies in our review were judged to have used an accurate reference st and ard . Conversely , the MRS literature frequently failed to specify the length of time between index and reference tests or that the clinicians were unaware of the index test findings when reporting the reference st and ard . There was good correlation ( rho = 0.78 ) between review ers in assessment of the overall number of quality criteria met . However , mean agreement for individual QUADAS questions was only fair ( kappa = 0.22 ) and ranged from no agreement beyond chance ( kappa < 0 ) to moderate agreement ( kappa = 0.58 ) . CONCLUSION Inter-rater reliability in our study was relatively low . Nevertheless , we believe that QUADAS potentially is a useful tool for highlighting the strengths and weaknesses of existing diagnostic accuracy studies . Low reliability suggests that different review ers will reach different conclusions if QUADAS is used to exclude " low- quality " articles from meta-analyses . We discuss methods for improving the validity and reliability of QUADAS |
11,259 | 18,070,120 | Despite the high survival rate of RBBs , technical complications like debonding are frequent .
This in turn means that a substantial amount of extra chair time may be needed following the incorporation of RBBs .
There is thus an urgent need for studies with a follow-up time of 10 years or more , to evaluate the long-term outcomes | OBJECTIVES The objectives of this systematic review were to assess the 5-year survival of resin-bonded bridges ( RBBs ) and to describe the incidence of technical and biological complications . | OBJECTIVES A clinical trial , involving 203 resin-bonded bridges ( RBBs ) was undertaken to investigate the influence of retainer-type and luting material on the survival of these restorations . METHODS For this evaluation , 157 patients were available ( 14 % of the original sample was lost to follow-up or excluded from the study following the stopping criteria ) . Fifty per cent of the patients were question ed concerning the fate of the RBBs and 59 % of question ed patients were examined clinical ly . The patients that were seen for examination were representatives of the experimental groups . The findings from the clinical examination were compared with the data obtained from the question naire . Missing data were censored at the date of the last available information . Kaplan-Meier estimates were calculated to assess the survivals at the endpoints and compared using Cox 's proportional hazards procedure . RESULTS A significant difference was found between perforated ( P-type ) and etched ( E-type ) RBBs ( P = 0.05 ) for original bonded restorations but not when rebonded RBBs were taken into account . The results of the survival analysis were : anterior P-type , 49 + /- 7 % after 10.5 years : anterior E-type , 57 + /- 7 % after 10.5 years ; posterior P-type , 18 + /- 11 % after 6.8 years ; posterior E-type , 37 + /- 13 % after 10.2 years . Survivals of RBBs that were rebonded once during the evaluation period were 62 + /- 9 % ( 11.0 years ) for anterior RBBs and 51 + /- 11 % ( 10.2 years ) for posterior RBBs . CONCLUSIONS The factor location ( anterior versus posterior ) was as in previous analyses , highly significant . Differences in survival between cementation material s were not significant The etched-cast restoration was introduced in 1980 , and a prospect i ve study was initiated in March 1981 to determine if resin-bonded prostheses would prove to be a long-term alternative to traditional complete and partial coverage restorations . All resin-bonded restorations placed since that time in the author 's private prosthodontic practice have been recorded in the study . The success rate of 127 restorations has been 92.9 % , with a mean longevity of 5 years and 8 months OBJECTIVES All-ceramic resin-bonded fixed partial dentures ( RBFPDs ) were introduced as a conservative treatment approach 15 years ago . The purpose of this prospect i ve study was to evaluate the long-term clinical survival of RBFPDs made with a conventional two-retainer design or a cantilever single-retainer design . METHOD AND MATERIAL S A total of 37 anterior RBFPDs were made from the glass-infiltrated alumina ceramic In-Ceram . Sixteen RBFPDs with a conventional two-retainer design were inserted in 14 patients , and 21 RBFPDs with a cantilever single-retainer design were inserted in 16 patients . Panavia or Panavia 21 were used as luting agents either after silica-coating and silanation or after air-abrasion only . Patients were recalled every year for a clinical examination to evaluate the restorations with regard to function and possible failures . The mean observation time in the two-retainer group was 75.8 months , and in the single-retainer group it was 51.7 months . RESULTS No restoration debonded . In the two-retainer group , one restoration was lost because it fractured after 3 months at both connectors and one restoration was removed alio loco accidentally . Also in this group , four RBFPDs fractured within 15 months after insertion at one connector , but the pontic remained in situ as a cantilever RBFPD for several years . In the single-retainer group , only one FPD fractured and was lost 48 months after insertion . The 5-year survival rate was 73.9 % in the two-retainer group and 92.3 % in the single-retainer group . When unilateral fracture of a FPD was taken as criterion for failure , the five-year survival rate decreased to 67.3 % in the two-retainer group . CONCLUSIONS Cantilever all-ceramic resin-bonded fixed partial dentures made from high-strength oxide ceramics present a promising treatment alternative to two-retainer RBFPDs in the anterior region This study evaluated posterior resin-bonded prostheses using inlays as retainers . Thirty-nine patients missing at least one premolar or first molar received 51 resin-bonded fixed partial dentures with high noble alloy inlay retainers and a metal ceramic pontic . Resin luting material bonding to the framework was secured by the Silicoating method ( 24 fixed partial dentures ) , lost sugar crystal method ( 13 fixed partial dentures ) , or tin plating ( 14 fixed partial dentures ) . Clinical examinations were performed 1 week , 1 month , 6 months , 1 year , 2 years , and 5 years after cementation . None of the fixed partial dentures with silicoating or sugar crystal impressions lost retention , whereas two of the tin-plated fixed partial dentures required replacement . Resin-bonded inlay-retained prostheses appear to be a favorable alternative to other types of fixed partial dentures Abstract Within the framework of an on-going prospect i ve clinical study begun in 1985 , 120 adhesive-fixed partial dentures ( AFPD ) continued to be examined . The manufacture and the fitting of the AFPDs were carried out following a st and ard procedure . The preparation technique and the metal framework conditioning ( silica-coating , s and blasting and electrochemical etching ) has varied throughout the duration of the study . Using Kaplan-Meier analysis , the survival rate was determined and an analysis of risk with regard to location factors ( anterior , posterior ; maxilla , m and ible ) , conditioning and preparation techniques ( retentive/non-retentive ) was determined using the Cox regression model . The location of the AFPD had no influence on the survival rate . The survival time was determined mainly by the preparation technique . Strict preparation of seating grooves and pin holes made a 95 % survival rate possible after 10 years ( Kaplan-Meier estimation ) . Without retention , the risk of failure increased by a factor of 3.7 A total of 382 resin bonded bridges and splints were fitted , in 309 patients , in a teaching hospital . The restorations were evaluated after a period ranging from 5 months to 8 years . During the evaluation period 125 restorations ( 33 % ) debonded of which 69 ( 55 % ) were rebonded . The survival rates of the rebonded restorations at first , second , third or fourth rebond , where necessary , did not differ from the survival rate of the same restorations up to the first debond . Restorations constructed using the Rochette design had a significantly higher debond rate than the other design s. However , since they also exhibited a high rebond rate Rochette restorations continued to perform well over the study period . Splints had a higher debond rate as did restorations placed in patients in the age group 11 to 20 years , restorations involving more than two abutment teeth , and restorations containing more than one tooth OBJECTIVES To assess prospect ively over 10 years the incidences of technical and /or biological complications and failures occurring in a cohort of consecutive partially edentulous patients with fixed reconstructions on implants of the ITI Dental Implant System . METHODS Eighty-nine patients were available , 34 ( 38.2 % ) were male , 55 ( 61.8 % ) were female . At the 10-year examination ( range 8 - 12 years ) , they were 58.9 years old ( range 28 - 88 years ) . RESULTS Single crowns ( SC ) : 48 patients had been restored with 69 SC on 69 implants . Five of the implants with the crowns were lost because of biological failures . Two crowns ( 2.9 % ) were remade because of technical failures . Total failure amounted to seven ( 10 % ) . Implant borne fixed partial dentures ( I-I FPD ) : In 29 patients who had been restored with 33 implant borne suprastructures , the total number of failed I-I FPD was 2 ( 6.1 % ) . Tooth-implant borne fixed partial dentures ( I-T FPD ) : In 21 patients , 22 mixed tooth-implant borne reconstructions were constructed . The number of failed FPD reached 7 ( 31.8 % ) . Statistically significantly fewer biological failures occurred with I-I FPD compared with the I-T FPDs ( ANOVA , Bonferroni , P=0.022 ) . The I-T FPDs experienced statistically significantly more frequent technical failures compared with the other two groups of suprastructures ( P=0.003 , 0.031 ) . Consequences of complications : The occurrence of loss of retention as a complication increased the odds ratio ( OR ) to 17.6 ( P<0.001 ) to end up in a technical failure . Similarly , the event of a porcelain fracture increased the OR for the suprastructure to be a failure at 10 years to 11.0 ( P < or = 0.004 ) . Treatment of periimplantitis increased the OR to 5.44 ( P < or = 0.011 ) to result in a biological failure compared with implants in which this type of treatment was not applied . CONCLUSION The three groups of suprastructures demonstrated marked differences in their patterns of failures and complications . Complications increased the risk for failure . Support by CRF , University of Berne , Switzerl and STATEMENT OF PROBLEM It is important to evaluate the long-term clinical performance of resin-bonded fixed partial dentures and extracoronal attachments for removable prostheses . PURPOSE A prospect i ve , long-term clinical study was conducted to evaluate the success of resin-bonded fixed partial dentures since 1985 and of resin-bonded extracoronal attachments from 1987 . METHODS Until 1993 , a total of 130 resin-bonded fixed partial dentures had been seated in 101 patients , as well as 12 removable partial dentures ( RPDs ) with 24 extracoronal retainers in 10 patients . The clinical treatment protocol and the laboratory procedures were st and ardized . By the end of 1993 , it was possible to reexamine 98 patients with a total of 127 resin-bonded fixed partial dentures and all 10 patients with removable partial dentures . The average time in function for the resin-bonded fixed partial dentures at the time of examination was 3.4 years and 2.3 years for the removable restorations . RESULTS During the period of observation , one retainer failed on six of the resin-bonded fixed partial dentures , which represents a failure rate of 4.7 % . Debonding of extracoronal attachments was recorded for 8.3 % of the total number of retainers . CONCLUSION The resin-bonded fixed partial denture technique can be considered to be a clinical ly reliable method of treatment , and permits the expansion of indications beyond a classical three-unit resin-bonded fixed partial denture . Long-term clinical success of removable partial dentures with resin-bonded extracoronal retainers warrants additional clinical studies OBJECTIVES The purpose of this clinical pilot study was to evaluate the resin bond to alumina ceramic in vivo when using a bonding method which had been shown to be successful in laboratory testing . METHODS Seventeen resin-bonded all-ceramic bridges and splints fabricated from a glass-infiltrated alumina ceramic were tribochemically silica coated and resin bonded to their abutment teeth . The patients were recalled every 6 months to evaluate the restorations with regard to function and possible failures . RESULTS Over a mean observation time of 3.8 + /- 1.6 years some ceramic fractures occurred . However , the resin bond between the teeth and the alumina ceramic always remained stable . CONCLUSIONS Silica coating of alumina ceramic result ed in a durable resin bond over up to 5 years OBJECTIVES A r and omized controlled clinical trial was undertaken , to study the influence of some patient- and operator-dependent variables on the survival of posterior resin-bonded bridges ( PRBBs ) and to assess the survival of replacement ' PRBBs . This report contains some of the results of the 5-year analysis . METHODS Survival was defined at three levels : ( 1 ) complete survival ( without any debonding ) , ( 2 ) functional survival ( i.e. survival after one loss of retention ) and ( 3 ) replacement survival ( survival of ' replacement ' PRBBs , inserted after rebonded bridges suffered a second dislodgement ) . Potential risk factors were analysed with Cox 's proportional hazards model and differences were tested for significance with the Breslow test . Observed effects are expressed as conditional-relative-risk ( CRR ) . Survival of ' replacement ' PRBBs was assessed with the Kaplan-Meier method . RESULTS Factors showing significant influences on complete survival were : ' location ' ( highest risk for m and ibular PRBBs : CRR = 2.2 ) , ' aetiology ' ( higher risk in treatment of aplasia : CRR = 2.9 ) , and ' time of existence ' ( open spaces existing less than 2 years before insertion of PRBB : CRR : 2.0 ) . The factor ' large open spaces in the m and ible ' was a risk for both complete and functional survival ( CCR values 3.1 and 3.5 , respectively ) . The survival of m and ibular and maxillary ' replacement ' PRBBs after 5 years was 19 + /- 7 % and 31 + /- 18 % , respectively . CONCLUSIONS Risk factors for PRBBs were : ' location ' , ' aetiology ' , ' time of existence ' , ' isolation method ' and ' large open spaces in the m and ible ' . M and ibular ' replacement ' PRBBs showed such an unacceptably low survival rate that fabrication is not recommended A clinical trial , concerning 203 resin-bonded bridges ( RBBs ) , was performed for investigation of the influence of retainer-type and cementation material s on the survival of these restorations . The survival rates after a 7.5-year follow-up were 75 % for anterior RBBs and 44 % for posterior bridges . Etched metal RBBs ( E-bridges ) were significantly more retentive than perforated RBBs ( P-bridges ) ; the survival rates were 78 % and 63 % , respectively . With respect to the cementation material s , Clearfil F , in combination with E-bridges , had the best overall survival ( 89 % , anterior and posterior ) . Maxillary anterior RBBs were more susceptible to failure than m and ibular anterior RBBs Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges . Improved bonding procedures and preparation design s , however , may have a positive effect on the functional durability of these restorations . The present study reports the final analysis of a r and omized controlled clinical trial in which different design s of posterior resin-bonded bridges were evaluated for a period of at least 5 years . The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations . Survival in this study was defined at two levels : ( 1 ) ' complete ' survival ( survival without any debonding ) , and ( 2 ) ' functional ' survival ( survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding ) . With regard to ' complete ' survival , no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth ( etching/Clearfil F2 , s and blasting/Panavia EX , and silica-coating/Microfill Pontic C ) . The variable ' preparation form ' ( conventional preparation form vs. modified preparation form ) for complete survival was statistically in favor of the modified preparation form ( 62 % vs. 46 % ) , but did not influence the functional survival . With regard to ' functional ' survival , the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems ( 90 % survival vs. 72 % and 75 % , p < 0.01 ) . Factor location was found to be highly significant for both survival levels [ Cox 's PH model , p = 0.0002 ( Cox , 1972 ) ] : The five-year ' complete ' survival rates were 65 % for maxillary restorations and 40 % for m and ibular restorations , while the five-year ' functional ' survival rates were 89 % and 68 % , respectively . It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival . Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the m and ible . The bonding systems used in this study appear to have no influence on the chance of failure . In rebonded posterior resin-bonded bridges , the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested |
11,260 | 12,639,084 | Such criteria result in good sensitivity but poor specificity .
Semi-Recumbent Patient Positioning Background and Practice Description Positioning of critically ill patients may affect the incidence of ventilator-associated pneumonia .
Supine patient positioning has been shown to be independently associated with the development of ventilator-associated pneumonia , possibly because of an increased risk for gastroesophageal reflux and aspiration ( 13 ) .
Semi-recumbent positioning ( defined as elevation of the head of the bed to 45 degrees ) may decrease the risk for ventilator-associated pneumonia .
Medications that alter the gastric pH , such as H2-antagonists and antacids , may increase organism counts and increase the risk for ventilator-associated pneumonia ( 18 ) .
Sucralfate , an alternative prophylactic agent that does not affect gastric pH , may not increase this risk .
Conclusions and Recommendations Stress ulcer prophylaxis with any agent may increase the risk for ventilator-associated pneumonia ( 18 ) .
Therefore , sucralfate may decrease risk when compared with H2-antagonists but not when compared with placebo .
The data comparing stress ulcer prophylaxis with sucralfate and H2-antagonists suggest a decreased | Ventilator-associated pneumonia is a common and highly morbid condition in critically ill patients ( 1 ) .
Epidemiologic investigations have shown cumulative incidence rates of 10 % to 25 % ( 1 - 3 ) , crude mortality rates of 10 % to 40 % ( 3 ) , and attributable mortality rates of 5 % to 27 % ( 4 , 5 ) .
Hospital length of stay and cost are both increased in patients who develop ventilator-associated pneumonia ( 5 , 6 ) .
Organisms causing ventilator-associated pneumonia generally fall into two groups : those causing early-onset ventilator-associated pneumonia ( < 4 days of mechanical ventilation ) and those causing late-onset ventilator-associated pneumonia ( 4 days of mechanical ventilation ) ( 2 , 3 ) .
Early-onset organisms are typically antibiotic-susceptible community-acquired bacteria , while late-onset organisms are commonly antibiotic-resistant nosocomial organisms .
Colonization of the oropharynx and the stomach with potentially pathogenic organisms precedes the development of ventilator-associated pneumonia in most patients ( 2 ) .
The pathogenesis of ventilator-associated pneumonia probably involves microaspiration of oropharyngeal or gastric secretions contaminated with these organisms ( 3 ) .
The most widely studied preventive strategies have focused on the prevention of oropharyngeal or gastric colonization and the prevention of aspiration of contaminated oropharyngeal or gastric secretions ( 3 , 6 - 11 ) .
This evidence -based systematic review aims to identify interventions for the prevention of ventilator-associated pneumonia , critically evaluate their efficacy and adverse effects , and recommend an approach to their use .
Stress Ulcer Prophylaxis Background and Practice Description Gastric colonization by potentially pathogenic organisms increases with decreasing gastric acidity ( 17 ) .
Summary of the Evidence Seven meta-analyses of more than 20 r and omized trials have addressed the risk for ventilator-associated pneumonia associated with various methods of stress ulcer prophylaxis ( 18 - 24 ) .
Potential for Harm and Cost Gastrointestinal bleeding in critically ill patients is associated with significant morbidity and mortality ( 25 ) .
Stress ulcer prophylaxis is therefore of importance in these patients . | BACKGROUND Patients with severe burns are at increased risk of developing methicillin-resistant Staphylococcus aureus ( MRSA ) ventilator-associated pneumonia . This study was design ed to determine whether MRSA pneumonia can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole ( TMP-SMX ) . METHODS We conducted a prospect i ve , r and omized , placebo-controlled study in patients with severe burns ( > or = 20 % ) , who required ventilator support . Prophylaxis was done with oral TMP-SMX ( 80 mg/400 mg ) three times daily for 10 days from 4 to 6 days after burn injury . The incidence of MRSA pneumonia and the side effects were evaluated during the administration period . RESULTS Twenty-one patients were assigned to receive TMP-SMX , and 19 patients to receive placebo . The incidence of MRSA pneumonia was 4.8 % in the TMP-SMX group and 36.8 % in the placebo group , showing a significant difference ( p = 0.017 ) . No major side effects of therapy were seen in the TMP-SMX group . CONCLUSION Prophylactic treatment with TMP-SMX can prevent MRSA pneumonia in severely burned patients Objective : To determine whether use of a single heat and moisture exchanger ( HME ) for ≤120 hrs affects efficiency , resistance , level of bacterial colonization , frequency rate of nosocomial pneumonia , and cost compared with changing the HME every 24 hrs . Design : Prospect i ve , controlled , r and omized , unblinded study . Setting : Surgical intensive care unit at a university teaching hospital . Patients : A total of 220 consecutive patients requiring mechanical ventilation for > 48 hrs . Interventions : Patients were r and omized to one of three groups : a ) hygroscopic HME ( Aqua+ ) changed every 24 hrs ( HHME‐24 ) ; b ) hydrophobic HME ( Duration HME ) changed every 120 hrs ( HME‐120 ) ; and c ) hygroscopic HME ( Aqua+ ) changed every 120 hrs ( HHME‐120 ) . Devices in all groups could be changed at the discretion of the staff when signs of occlusion or increased resistance were identified . Measurements and Main Results : Daily measurements of inspired gas temperature , inspired relative humidity , and device resistance were made . Additionally , daily cultures of the patient side of the device were accomplished . The frequency rate of nosocomial pneumonia was made by using clinical criteria . Ventilatory support variables , airway care , device costs , and clinical indicators of humidification efficiency ( sputum volume , sputum efficiency ) were also recorded . Prolonged use of both hygroscopic and hydrophobic devices did not diminish efficiency or increase resistance . There was no difference in the number of colony‐forming units from device cultures over the 5‐day period and no difference between colony‐forming units in devices changed every 24 hrs compared with devices changed after 120 hrs . The average duration of use was 23 ± 4 hrs in the HHME‐24 group , 73 ± 13 hrs in the HME‐120 group , and 74 ± 9 hrs in the HHME‐120 group . Mean absolute humidity was greater for the hygroscopic devices ( 30.4 ± 1.1 mg of H2O/L ) compared with the hydrophobic devices ( 27.8 ± 1.3 mg of H2O/L ) . The frequency rate of nosocomial pneumonia was 8 % ( 8:100 ) in the HHME‐24 group , 8.3 % ( 5:60 ) in the HME‐120 group , and 6.6 % ( 4:60 ) in the HHME‐120 group . Pneumonia rates per 1000 ventilatory support days were 20:1000 in the HHME‐24 group , 20.8:1000 in the HME‐120 group , and 16.6:1000 in the HHME‐120 group . Costs per day were $ 3.24 for the HHME‐24 group , $ 2.98 for the HME‐120 group , and $ 1.65 for the HHME‐120 group . Conclusions : Changing the hydrophobic or hygroscopic HME after 3 days does not diminish efficiency , increase resistance , or alter bacterial colonization . The frequency rate of nosocomial pneumonia was also unchanged . Use of HMEs for > 24 hrs , up to 72 hrs , is safe and cost effective Nosocomial pneumonia is the leading cause of death among all hospital-acquired infections [ 1 ] . The estimated incidence of nosocomial pneumonia in intensive care units ranges from 10 % to 65 % ; most studies [ 2 - 6 ] show case fatality rates of more than 20 % . Ventilator-associated pneumonia specifically refers to nosocomial pneumonia that develops in a mechanically ventilated patient and that was not present at the time of airway intubation [ 7 ] . Various clinical risk factors have been associated with an increased incidence of ventilator-associated pneumonia , either because they predispose the patient to bacterial colonization of the oropharynx and stomach ( for example , the administration of antacids or histamine-2-receptor antagonists ) or because they facilitate aspiration of contaminated contents from these sites ( for example , supine positioning ) [ 1 , 2 , 8 , 9 ] . Craven and colleagues [ 10 ] first showed that the frequency of ventilator circuit changes also influences the incidence of ventilator-associated pneumonia . They found that changing circuits every 24 rather than every 48 hours was independently associated with the occurrence of nosocomial pneumonia [ 10 ] . This association has been attributed to increased manipulation of the patient , the endotracheal tube , and the ventilator circuit , which results in increased aspiration of contaminated tubing condensate or upper airway secretions [ 10 , 11 ] . More recently , several groups of investigators have found that ventilator circuits can be used safely for more than 48 hours without increasing the incidence of nosocomial pneumonia [ 12 - 16 ] . However , because of limitations in the design of these studies and the small number of patients prospect ively examined , the Centers for Disease Control and Prevention has given no clear recommendation for the maximum length of time that ventilator circuits can safely be left in place during prolonged mechanical ventilation [ 17 ] . This has result ed in the development of ambiguous guidelines about the frequency with which ventilator circuits should be changed [ 18 , 19 ] and in a call for well- design ed investigations to resolve this issue [ 20 ] . We did a r and omized , controlled trial to compare the effect and cost-efficacy of routine and no routine ventilator circuit changes in patients having prolonged mechanical ventilation . Our main goals were to determine 1 ) the incidence and outcome of ventilator-associated pneumonia in patients receiving scheduled ventilator circuit changes and 2 ) whether this incidence was increased in patients whose ventilator circuits remained unchanged . Methods Study Location and Patients The study was conducted at two university-affiliated teaching hospitals : Barnes Hospital ( 900 beds ) and Jewish Hospital ( 450 beds ) . During a 7-month period ( June 1994 to December 1994 ) , all patients receiving mechanical ventilation in the intensive care units of these hospitals ( surgical , trauma , medical , cardiothoracic , and neurosurgical units at Barnes Hospital ; surgical , medical , and cardiothoracic units at Jewish Hospital ) were potentially eligible for this investigation . Patients were entered into the trial if they were older than 18 years and had received mechanical ventilation for more than 5 days . Mechanical ventilation for more than 5 days was predetermined , on the basis of our previous experience at these institutions [ 2 , 21 ] , to be necessary so that a more homogeneous cohort of patients requiring prolonged mechanical ventilation could be accrued . Patients were excluded if they were likely to be extubated within 24 hours of r and omization , if they had transferred from other hospitals and had already received mechanical ventilation for more than 24 hours , if they had had lung transplantation , or if they had active hemoptysis . Barnes Hospital and Jewish Hospital share the same respiratory therapy and infection control departments . The study was approved by the Washington University School of Medicine Human Studies Committee and the Institutional Review Board of Jewish Hospital . Both waived the requirement for informed consent because this study was a quality assessment of two low-risk practice s already in clinical use . Study Design Patients were r and omly assigned to receive no routine ventilator circuit changes or circuit changes every 7 days within 24 hours of meeting eligibility criteria . A schedule of changing ventilator circuits every 7 days was selected on the basis of available clinical data [ 12 - 16 ] and our survey of 16 regional medical centers ( DM Baker . Unpublished communication ) . Stratification according to hospital site was done before r and omization to control for differences in patient population s and health care personnel . R and omization within each hospital was done using opaque , sealed envelopes , which were opened at the time each patient was enrolled in the study . For the purpose s of this investigation , ventilator circuits were defined to include gas delivery tubing , humidifier water reservoirs , water traps , and medication delivery devices ( such as metered-dose inhaler chambers or adapters ) . Ventilator circuits could be changed at any time , at the discretion of individual care providers ( physicians , nurses , and respiratory therapists ) , secondary to a mechanical failure of the ventilator circuit ( such as an air leak ) or visible soil ( such as that result ing from hemoptysis or aspirated emesis ) . Scheduled ventilator circuit changes were done during the evening or night shifts to minimize the identification of individual patient group assignments to blinded investigators . All nonscheduled circuit changes were done when an appropriate indication for the circuit change ( that is , a mechanical defect or soil ) was identified . Patients transferred to the operating room for a surgical procedure ( such as tracheotomy ) or to diagnostic radiology received the same mechanical ventilator and circuit when they returned to the intensive care unit . The ventilators used for this study included Siemens Servo 900C ( Siemens-Elema Ventilator Systems , Schaumburg , Illinois ) , Puritan-Bennett 700 Series ( Puritan-Bennett Corporation , Carlsbad , California ) , and Bird 8400 Series ventilators ( Bird Products Corporation , Palm Springs , California ) . All ventilators were equipped with wick-type humidifiers ( Concha Therm III Plus , Hudson Respiratory Care , Inc. , Temecula , California ) filled with sterile irrigation water . All ventilator circuits were disposable ( Hudson Respiratory Care , Inc. , model 1613 ) and equipped with Y connectors . Each ventilator circuit had an attached trap for the collection of tubing condensate ( Marquest Medical Products , Inc. , Englewood , Colorado ) . As per our st and ard procedure , all ventilator circuits were monitored at least every 2 hours and water traps were emptied when full . Data Collection For all study patients , the following characteristics were prospect ively recorded by one of the investigators : age , sex , diagnosis at hospital admission , indication for mechanical ventilation , Premorbid Lifestyle score , the ratio of arterial blood oxygen tension to the concentration of inspired oxygen ( Pao 2 : Fio 2 ) , severity of illness based on APACHE II ( Acute Physiology and Chronic Health Evaluation [ 22 ] ) scores , the Organ System Failure Index , and the occurrence of a witnessed aspiration event . Specific processes of medical care examined to assess risk factors for ventilator-associated pneumonia were the administration of antacids or histamine-2-receptor antagonists , pharmacologic aerosol treatments during mechanical ventilation ( such as bronchodilators , antibiotics , and mucolytics ) , fiberoptic bronchoscopy , surgical tracheostomy , and the number of ventilator circuit changes done and the indications for those changes ( scheduled according to the study protocol , soil , or mechanical defect ) . Two of the investigators made daily rounds in the intensive care units of each hospital to identify eligible patients . Patients entered into the study were prospect ively followed for the occurrence of ventilator-associated pneumonia until they were successfully weaned from mechanical ventilation , were discharged from the hospital , or died . All patients suspected by these investigators of having ventilator-associated pneumonia were prospect ively and independently review ed by another investigator who was blinded to the patient 's treatment group assignment . The diagnosis of ventilator-associated pneumonia was strictly based on the predetermined criteria described below . Patients could not be entered into the study more than once during the same hospitalization , and only the first episode of ventilator-associated pneumonia was evaluated . In addition to the occurrence of ventilator-associated pneumonia , secondary outcomes assessed included the length of hospitalization , the duration of mechanical ventilation , hospital mortality , and mortality directly attributed to ventilator-associated pneumonia . All study variables were recorded in data collection books maintained at each of the participating hospitals . Definitions All definitions were selected prospect ively as part of the original study design . The Premorbid Lifestyle score was used as previously defined [ 23 ] : Zero indicated that the patient was employed without restriction ; 1 indicated that the patient was independent , fully ambulatory , not employed , or employed with restriction ; 2 indicated that the patient had restricted activities , could live alone and get out of the house to do basic necessities , or had severely limited exercise ability ; 3 indicated that the patient was housebound , could not get out of the house unassisted , could not live alone , or could not do heavy chores ; and 4 indicated that the patient was bed- or chairbound . We calculated APACHE II scores on the basis of clinical data available from the 24-hour period before study enrollment ( day 5 of mechanical ventilation ) . The Organ System Failure Index was modified from that used by Rubin and coworkers [ 24 ] . One point was given for Nosocomial pneumonia develops in 0.5 to 1 patient per 100 hospital admissions and is associated with high morbidity and mortality [ 1 , 2 ] . Mechanically ventilated patients have a high risk for developing nosocomial pneumonia ; indeed , ventilator-associated pneumonia has a cumulative incidence ranging from 18 % to 60 % , and it was found in more than 70 % of patients who died of acute lung injury [ 3 - 6 ] . Nosocomial pneumonia is frequently caused by gram-negative bacilli and usually results from aspiration of bacteria from the colonized oropharynx [ 7 - 9 ] . Colonization of the pharynx by gram-negative bacilli [ 9 - 12 ] is associated with chronic illness and previous use of antibiotic agents and endotracheal intubation ; in the pathogenesis of ventilator-associated pneumonia , the relation between chronic aspiration of colonized secretions through a tracheal cuff and the development of pneumonia is well established [ 13 , 14 ] . Several strategies , such as infection-control measures ( for example , h and -washing ) [ 15 , 16 ] , preservation of a normal gastric pH , or topical administration of a nonabsorbable antibiotic combination ( selective digestive decontamination ) have been recommended to decrease the incidence of ventilator-associated pneumonia [ 17 - 19 ] . However , further investigation is required to define the role of selective digestive decontamination in selected patients in intensive care units ; in addition , there is considerable concern about the risk for selection of resistant strains . Recently , two studies suggested the possibility of preventing the chronic aspiration of subglottic secretions either by changes in body position [ 20 ] or by manual intermittent aspiration of subglottic secretions [ 21 ] , two alternative approaches for preventing ventilator-associated pneumonia . We evaluated the usefulness of continuous aspiration of subglottic secretions in the prevention of ventilator-associated pneumonia in a medicalsurgical intensive care unit . Methods Patients All patients admitted to the intensive care unit of the Sabadell Hospital from June 1990 to March 1993 who required intubation and were expected to receive mechanical ventilation for at least 72 hours were eligible for study . The intubation could be done either in the intensive care unit or in the emergency department . Patients were excluded if they were intubated in other areas of the hospital , if they carried a tracheostomy tube , or if they developed a pneumonia or died during the first 72 hours of mechanical ventilation . Study was considered complete when a patient was extubated , when a tracheostomy was done , when a patient died , or when ventilator-associated pneumonia was diagnosed . The follow-up period consisted of the patient 's remaining stay in the intensive care unit . All patients were intubated with the same type of endotracheal tube ( Hi-Lo Evac ; Mallinckrodt Laboratories , Athlone , Irel and ) , which incorporates a dorsal separate lumen ending into the subglottic area by creating a large elliptical dorsal opening above the cuff for aspiration of subglottic secretions ( Figure 1 ) . The size of each endotracheal tube was selected by the attending physician ; after intubation , the correct position of endotracheal tube was verified by a roentgenogram of the chest . Figure 1 . Diagram of continuous aspiration of subglottic secretions . Patients were r and omly assigned to receive continuous aspiration through the additional lumen from the endotracheal tube ( case- patients ) or to receive st and ard treatment in which the additional lumen remained closed ( control patients ) . Intra-cuff pressure was monitored every 4 hours ( Mallinckrodt GmbH , Mallinckrodt Laboratories , Neunkirchen-Seelscheid , Germany ) and was kept above 20 mm Hg . Subglottic drainage was continuous , and secretions were collected in a mucous collector ( Mocstrap ; Proclinics , Barcelona , Spain ) . The amount of secretions obtained daily was also recorded . If subglottic drainage was negative , the permeability was checked every 4 hours by injecting sterile saline serum into the evacuation lumen . All patients received stress ulcer prophylaxis with sucralfate . We did not use a selective decontamination regimen or antibiotic prophylaxis . The study protocol was review ed and approved by the hospital 's institutional review board for human studies . Data Collection and Definitions We prospect ively recorded each patient 's demographic characteristics , diagnosis at admission , and underlying diseases . The Acute Physiology and Chronic Health Evaluation ( APACHE ) II scoring system of Knaus and colleagues [ 22 ] was used to assess the severity of an acute illness . Several risk factors for ventilator-associated pneumonia were recorded , such as continuous sedation , previous surgery , multiple trauma , structural or pharmacologic coma ( score of 8 according to the Glasgow coma scale [ 23 ] ) , and use of muscle relaxants and antibiotic treatment during the intensive care unit stay . Ventilator-associated pneumonia was suspected in patients who met the following criteria after 72 hours of mechanical ventilation : fever ( body temperature 38.3 C ) , leukocytosis ( > 12 000 leukocytes/mm3 ) or leukopenia ( < 4000 leukocytes/mm3 ) , purulent secretions , and the presence of new and persistent pulmonary infiltrates . The diagnosis of pneumonia was confirmed by a positive protected specimen brush culture containing 103 colony-forming units (CFU)/mL or more , a positive bronchoalveolar lavage culture with 104 CFU/mL or more , or by a good clinical response to antibiotic agents . Additional criteria were the absence of a diagnosis other than pneumonia and pathologic findings consistent with pneumonia in patients who died and in whom autopsy was authorized . Ventilator-associated pneumonia was histologically diagnosed when foci of consolidation with intense polymorphonuclear leukocyte accumulation in the bronchioles and alveolar spaces were observed . Roentgenograms of the chest were interpreted by a radiologist who had no knowledge of patients ' treatment groups . Crude mortality rates included all deaths that occurred in the intensive care unit in patients with ventilator-associated pneumonia . Death was considered attributable to the pulmonary infection if the patient died before having any objective response to antimicrobial therapy or if the pulmonary infection was considered a contributing factor to death in patients with additional conditions . We used the definitions described by Knaus and colleagues [ 22 ] to define the underlying diseases . We considered previous surgery when a surgical procedure had been done within the present admission to the hospital and considered previous antibiotic treatment when a patient was receiving antibiotic agents at r and omization . Bacteriologic Examination In patients in whom ventilator-associated pneumonia was suspected , bronchoscopy was done while they were being ventilated with an Fio 2 of 1.0 and without positive end-expiratory pressure . All patients received midazolam as a sedative and atracurium as a relaxant while the bronchoscopy was done . The fiberoptic bronchoscope ( Olympus BF 20 ; Olympus Corp. , Tokyo , Japan ) was passed into the trachea through the endotracheal tube by a special connector ( Unimed Ltd. , Shaftesbury , United Kingdom ) and was advanced under visual control to the bronchial orifice of the abnormal lobe . The telescoping plugged catheter ( TAG Medical , Bobigny Cedex , France ) was inserted through the inner suction channel and was advanced to a wedged peripheral position . Airway secretions were obtained using a previously described technique [ 24 ] . For a bronchoalveolar lavage , the bronchoscope was sustained in a wedged position , and lavage was done with three 50-mL aliquots of sterile isotonic saline . The bronchoscope was then removed , and ventilation with an Fio 2 of 1.0 was continued for 15 minutes . After the protected specimen brush was transected into a sterile vial containing 1 mL of sterile lactate Ringer 's solution , the vial was vigorously agitated for at least 60 seconds to suspend all the material from the brush . Specimens were immediately sent to the laboratory for quantitative cultures . Aliquots of 0.01 mL were then taken from the original suspension and inoculated into blood agar , chocolate agar , anaerobic kanamicin blood agar , anaerobic blood agar , MacConkey agar , buffered charcoal yeast extract agar , and Sabouraud media . One 0.001-mL aliquot was also inoculated into chocolate agar media . Culture plates were incubated at 37 C under adequate aerobic and anaerobic conditions ; all plates except for the Sabouraud plates were evaluated for growth at 24 and 48 hours . For the protected specimen brush , bacterial counts of 103 CFU/mL or greater were used as the cutoff point to diagnose pneumonia . Two serial 10-fold dilutions were then done on the recovered bronchoalveolar lavage fluid , and 0.01-mL aliquots of the original suspension and each dilution were placed onto plates in the same way as for the protected specimen brush sample . All protected specimen brush and bronchoalveolar lavage fluid isolates were identified by st and ard laboratory techniques [ 25 ] . Two blood cultures were done simultaneously in all patients , as were pleural fluid cultures if present . Surveillance cultures for aerobic microorganisms in the subglottic secretions were obtained from patients in the continuous aspiration group and were repeated every 5 days until ventilator-associated pneumonia developed or until patients were extubated or died . Statistical Analysis We compared the characteristics of the two groups using the Student t-test or Mann-Whitney test for continuous variables and the chi-square test or Fisher exact test for categorical variables . We defined the cumulative incidence as the number of events divided by the number of patients and estimated risk ratios and 95 % CIs [ 26 ] . The incidence rate was defined as the number of events divided by the number of days the patient was at risk because of the presence of an endotracheal tube . We compared Circuits on mechanical ventilators with cascade humidifiers are routinely changed every day or every other day , although humidifying cascades have been considered unlikely to increase the risk of respiratory infection because they do not generate aerosols . Moreover , changing ventilator tubings every 24 rather than every 48 h increases the risk of ventilator-associated pneumonia . To study the effects of ventilator circuit changes on the rate of nosocomial pneumonia and on patient and circuit colonization , 73 consecutive patients requiring continuous mechanical ventilation for more than 48 h were r and omly assigned to either ventilator circuit changes every 48 h ( Group 1 , n = 38 ) or no change ( Group 2 , n = 35 ) . Patients dying or being weaned before 96 h were not analyzed ( Group 1 n = 3 ; Group 2 n = 7 ; leaving Group 1 n = 35 and Group 2 n = 28 ; p = 0.13 ) . Ventilator-associated pneumonia was defined as the occurrence during mechanical ventilation or within 48 h after weaning of a new and persistent infiltrate on chest X-ray , purulent tracheal secretions , and a positive culture of a protected brush specimen ( greater than or equal to 10(3 ) cfu/ml ) . Bacterial colonization was assessed every 48 h by quantitative cultures of pharyngeal swab , tracheal aspirate , humidifying cascade , and expiratory tubing trap . The two groups were similar in terms of age , indication for and duration of ventilation , and severity of illness . ( ABSTRACT TRUNCATED AT 250 WORDS We performed a prospect i ve observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals . Protected bronchoscopic techniques ( protected specimen brush and bronchoalveolar lavage ) were used for diagnosis to minimize misclassification . Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis . Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8 % and incidence rates of 12.5 cases per 1 , 000 patient days and 20.5 cases per 1,000 ventilator days . Staphylococcus aureus , Streptococcus pneumoniae , Pseudomonas aeruginosa , and Hemophilus species made up 65 % of isolates from the lower respiratory tract , whereas only 12.5 % of isolates were enteric gram-negative bacilli . Daily surveillance cultures of the nares , oropharynx , trachea , and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5 % , whereas gastric colonization preceded tracheal colonization for only four of 31 ( 13 % ) eventual pathogens . By multiple logistic regression , independent risk factors for ventilator- associated pneumonia were admission serum albumin < = 2.2 g/dl ( odds ratio [ OR ] 5.9 ; 95 % confidence interval [ CI ] 2.0 - 17.6 ; p = 0.0013 ) , maximum positive end-expiratory pressure > = 7.5 cm H2O ( OR , 4.6 ; 95 % CI , 1.4 to 15.1 ; p = 0.012 ) , absence of antibiotic therapy ( OR , 6.7 ; 95 % CI , 1.8 to 25.3 ; p = 0.0054 ) , colonization of the upper respiratory tract by respiratory gram-negative bacilli ( OR , 3.4 ; 95 % CI , 1.1 to 10.1 ; p = 0.028 ) , pack-years of smoking ( OR , 2.3 for 50 pack-years ; 95 % CI , 1 . 2 to 4.2 ; p = 0.012 ) , and duration of mechanical ventilation ( OR , 3 . 4 for 14 d ; 95 % CI , 1.5 to 7.8 ; p = 0.0044 ) . Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention BACKGROUND Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers . There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding , ventilator-associated pneumonia , and mortality . METHODS In a multicenter , r and omized , blinded , placebo-controlled trial , we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation . Patients received either nasogastric sucralfate suspension ( 1 g every six hours ) and an intravenous placebo or intravenous ranitidine ( 50 mg every eight hours ) and a nasogastric placebo . RESULTS The patients in the two groups had similar base-line characteristics . Clinical ly important gastrointestinal bleeding developed in 10 of 596 ( 1.7 percent ) of the patients receiving ranitidine , as compared with 23 of 604 ( 3.8 percent ) of those receiving sucralfate ( relative risk , 0.44 ; 95 percent confidence interval , 0.21 to 0.92 ; P=0.02 ) . In the ranitidine group , 114 of 596 patients ( 19.1 percent ) had ventilator-associated pneumonia , as compared with 98 of 604 ( 16.2 percent ) in the sucralfate group ( relative risk , 1.18 ; 95 percent confidence interval , 0.92 to 1.51 ; P=0.19 ) . There was no significant difference between the groups in mortality in the intensive care unit ( ICU ) ( 23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group ) or the duration of the stay in the ICU ( median , nine days in both groups ) . CONCLUSIONS Among critically ill patients requiring mechanical ventilation , those receiving ranitidine had a significantly lower rate of clinical ly important gastrointestinal bleeding than those treated with sucralfate . There were no significant differences in the rates of ventilator-associated pneumonia , the duration of the stay in the ICU , or mortality OBJECTIVES To compare the incidence of pulmonary complications and hospital re source utilisation in patients treated with continuous rotation therapy versus manual turning in a traditional hospital bed . DESIGN Prospect i ve , r and omised clinical trial . SETTING Surgical intensive care unit of a large , tertiary care , urban hospital . PATIENTS One-hundred- and -thirty-seven consecutive injured patients admitted to the Surgical Intensive Care Unit were prospect ively r and omised to receive either the Rotorest Kinetic Treatment Table or a traditional hospital bed . One hundred of these patients met the study criteria and are the basis of this report . METHODS The patients ' medical records were review ed in a prospect i ve manner to determine the frequency and severity of pulmonary complications and re source utilisation in the two patient groups . MAIN RESULTS There were no significant differences in the minimum , average , or maximum pO 2 , pCO 2 , PEEP , IMV rate , or pre-extubation blood gases during the first seven days of the study . Fewer cardiac output measurements , arterial blood gas measurements , chest X-rays , respiratory therapies , hours intubated , days in the ICU , days in the step-down unit , days in the hospital , and lower ICU charges , respiratory care charges , and total hospital charges were utilised in the patients treated with the kinetic bed . The incidence of pulmonary event complications and process complications was lower in the group of patients treated on the Rotorest bed . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To compare turning by an oscillating bed to st and ard 2-hour turning . Outcomes were survival , length of stay ( LOS ) , duration of mechanical ventilation , and incidence of pneumonia . METHODS One hundred and three intensive care patients were r and omly assigned to st and ard turning or turning by an oscillating bed . Data , collected at baseline , daily for 7 days , and then three times weekly until study discharge , included demographics , initial Acute Physiology and Chronic Health Evaluation ( APACHE II ) score , ventilatory/gas exchange parameters , indicators of pneumonia , nursing measures , and chest roentgenograph . RESULTS There were no significant differences for LOS , duration of ventilation , nor incidence of pneumonia . Higher survival for subjects on the oscillating bed reached borderline significance ( P = .056 ) for subjects with APACHE II greater than or equal to 20 . Longitudinal data were analyzed using the r and om effects model . No differences in ventilatory or gas exchange parameters were identified . Among subjects who developed pneumonia there was a significantly higher respiratory score ( nursing acuity scale ) for subjects on the oscillating bed . CONCLUSIONS In selected critically ill patients oscillating therapy may improve survival and improve airway clearance . The frequency and degree of turning needed to prevent complications and improve outcome remains unclear . These newer beds should be used with discrimination so as to not increase hospital costs unnecessarily BACKGROUND Risk factors for nosocomial pneumonia , such as gastro-oesophageal reflux and subsequent aspiration , can be reduced by semirecumbent body position in intensive-care patients . The objective of this study was to assess whether the incidence of nosocomial pneumonia can also be reduced by this measure . METHODS This trial was stopped after the planned interim analysis . 86 intubated and mechanically ventilated patients of one medical and one respiratory intensive-care unit at a tertiary-care university hospital were r and omly assigned to semirecumbent ( n=39 ) or supine ( n=47 ) body position . The frequency of clinical ly suspected and microbiologically confirmed nosocomial pneumonia ( clinical plus quantitative bacteriological criteria ) was assessed in both groups . Body position was analysed together with known risk factors for nosocomial pneumonia . FINDINGS The frequency of clinical ly suspected nosocomial pneumonia was lower in the semirecumbent group than in the supine group ( three of 39 [ 8 % ] vs 16 of 47 [ 34 % ] ; 95 % CI for difference 10.0 - 42.0 , p=0.003 ) . This was also true for microbiologically confirmed pneumonia ( semirecumbent 2/39 [ 5 % ] vs supine 11/47 [ 23 % ] ; 4.2 - 31.8 , p=0.018 ) . Supine body position ( odds ratio 6.8 [ 1.7 - 26.7 ] , p=0.006 ) and enteral nutrition ( 5.7 [ 1.5 - 22.8 ] , p=0.013 ) were independent risk factors for nosocomial pneumonia and the frequency was highest for patients receiving enteral nutrition in the supine body position ( 14/28 , 50 % ) . Mechanical ventilation for 7 days or more ( 10.9 [ 3.0 - 40.4 ] , p=0.001 ) and a Glasgow coma scale score of less than 9 were additional risk factors . INTERPRETATION The semirecumbent body position reduces frequency and risk of nosocomial pneumonia , especially in patients who receive enteral nutrition . The risk of nosocomial pneumonia is increased by long- duration mechanical ventilation and decreased consciousness STUDY OBJECTIVES To prospect ively identify the occurrence of ventilator-associated pneumonia ( VAP ) in a community hospital , and to determine the risk factors for VAP and the influence of VAP on patient outcomes in a nonteaching institution . DESIGN Prospect i ve cohort study . SETTING A medical ICU and a surgical ICU in a 500-bed private community nonteaching hospital : Missouri Baptist Hospital . PATIENTS Between March 1998 and December 1999 , all patients receiving mechanical ventilation who were admitted to the ICU setting were prospect ively evaluated . INTERVENTION Prospect i ve patient surveillance and data collection . RESULTS During a 22-month period , 3,171 patients were admitted to the medical and surgical ICUs . Eight hundred eighty patients ( 27.8 % ) received mechanical ventilation . VAP developed in 132 patients ( 15.0 % ) receiving mechanical ventilation . Three hundred one patients ( 34.2 % ) who received mechanical ventilation died during hospitalization . Logistic regression analysis demonstrated that tracheostomy ( adjusted odds ratio [ AOR ] , 6.71 ; 95 % confidence interval [ CI ] , 3.91 to 11.50 ; p < 0.001 ) , multiple central venous line insertions ( AOR , 4.20 ; 95 % CI , 2.72 to 6.48 ; p < 0.001 ) , reintubation ( AOR , 2.88 ; 95 % CI , 1.78 to 4.66 ; p < 0.001 ) , and the use of antacids ( AOR , 2.81 ; 95 % CI , 1.19 to 6.64 ; p = 0.019 ) were independently associated with the development of VAP . The hospital mortality of patients with VAP was significantly greater than the mortality of patients without VAP ( 45.5 % vs 32.2 % , respectively ; p = 0.004 ) . The occurrence of bacteremia , compromised immune system , higher APACHE ( acute physiology and chronic health evaluation ) II scores , and older age were identified as independent predictors of hospital mortality . CONCLUSIONS These data suggest that VAP is a common nosocomial infection in the community hospital setting . The risk factors for the development of VAP and risk factors for hospital mortality in a community hospital are similar to those identified from university-affiliated hospitals . These risk factors can potentially be employed to develop local strategies for the prevention of VAP . CLINICAL IMPLICATION S ICU clinicians should be aware of the risk factors associated with the development of VAP and the impact of VAP on clinical outcomes . More importantly , they should cooperate in the development of local multidisciplinary strategies aim ed at the prevention of VAP and other nosocomial infections Objective : To determine whether metoclopramide prevents nosocomial pneumonia in intensive care unit ( ICU ) patients receiving enteral feeding by a nasogastric tube . Design : Prospect i ve , r and omized , controlled trial . Setting : ICU of a university hospital . Patients : A total of 305 consecutive patients requiring placement of a nasogastric tube for > 24 hrs . Interventions : Patients were r and omized to receive either 10 mg of metoclopramide or placebo at 8‐hr intervals through the nasogastric tube . Measurements and Main Results : A total of 174 patients received placebo and 131 received metoclopramide . Baseline characteristics in the two treatment groups were comparable . Of the 305 patients , 46 developed nosocomial pneumonia , which was 24 patients ( 13.7 % ) in the placebo group and 22 ( 16.8 % ) in the metoclopramide group ( p > .05 ) . Patients in the placebo group developed pneumonia earlier than patients receiving metoclopramide ( 4.46 ± 1.72 days [ mean ± SD[rsqb ] after ICU admission compared with 5.95 ± 1.78 days ; p = .006 ) . Subgroup analysis showed that metoclopramide did not reduce the frequency rate of pneumonia in patients with tracheal intubation ( 19 [ 25.3 % ] of 75 patients receiving metoclopramide vs. 21 [ 21.2 % ] of 99 patients receiving placebo ) or those receiving mechanical ventilation ( 17 [ 25.6 % ] of 58 patients receiving metoclopramide vs. 20 [ 29.3 % ] of 78 patients receiving placebo ) . The mortality rate also did not differ in the two treatments groups ( 56 % in the metoclopramide group vs. 53 % in the placebo group ; p > .05 ) . Conclusions : Although metoclopramide delayed the development of nosocomial pneumonia , it did not decrease its frequency rate and had no effect on the mortality rate in critically ill patients receiving nasogastric enteral feeding Background Enteral feeding provides nutrients for patients who require endotracheal tubes and mechanical ventilation . There is a presumed increase in the risk of ventilator-associated pneumonia ( VAP ) with tube feeding . This has stimulated the development of procedures for duodenal intubation and small intestinal ( SI ) feeding as primary prophylaxes to prevent VAP . Objective To investigate the rate of VAP and adequacy of nutrient delivery with gastric ( G ) vs. SI feeding . Design A prospect i ve , r and omized , controlled trial . Setting A medical intensive care unit of a county hospital . Patients A total of 44 endotracheally intubated , mechanically ventilated patients requiring enteral nutrition . Intervention Subjects were r and omized to receive enteral nutrition via G or SI feeding . Protocol s directed the placement of the feeding tube and the infusion of enteral nutrition and defined the radiographic and clinical criteria for a diagnosis of VAP . Measurements and Outcomes The incidence of VAP and the adequacy of nutritional supplementation were prospect ively followed . The relative risk of VAP with SI was 1.1 ( 95 % confidence interval 0.96–2.44 ) compared with G. The SI group received a greater percentage of their caloric requirements ( SI 69 ± 7 % vs. G 47 ± 7 % , mean ± sem , p < .05 ) . Mortality did not differ between G ( 26 ± 9 % ) and SI ( 24 ± 10 , p = .86 ) . Conclusions There is no clear difference in the incidence of VAP in SI compared with G enteral nutrition . Patients given feeding into the SI do receive higher calorie and protein intakes STUDY OBJECTIVE The aims of the study were to evaluate the technique of selective digestion decontamination ( SDD ) in preventing the development of nosocomial infections in a selected population and to assess the effects on colonization of the oropharynx , nares , and bronchi . A financial assessment was also performed . DESIGN Prospect i ve , double-blind , r and omized placebo-controlled trial using amphotericin B , colistin sulfate ( polymixin E ) , and gentamicin applied to the nares , the oropharynx , and enterally ; no parenteral antibiotics were given during the study period . The SDD was applied every 6 h during the study period . SETTING Multidisciplinary ICU in a university hospital . PATIENTS A total of 148 trauma patients admitted emergently and intubated within less than 24 h were enrolled . Seventy-two patients who received placebo and 76 treated patients were analyzed on an " intention-to-treat " basis . INTERVENTIONS Microbiologic surveillance sample s of oropharyngeal and bronchial secretions , urine , and any other potentially infected sites were taken at the time of ICU admission and twice weekly thereafter until discharge from the unit . MEASUREMENTS AND RESULTS With the use of SDD , colonization was significantly reduced in the oropharynx and nares ( < 0.05 ) but not in bronchi . However , episodes of bronchopneumonia were significantly reduced ( 19 in the active group vs 37 in the placebo group ; p,0.01 ) . Staphylococcus aureus remained the main potential pathogen causing bronchial colonization and subsequent bronchopneumonia . There was no reduction in the incidence of other infections . Days in the ICU , duration of mechanical ventilation , and mortality rate were unchanged . After the use of SDD , Gram-positive colonization tended to increase and this was mainly due to methicillin-resistant coagulase-negative staphylococci . The total cost of antibiotic therapy ( $ 62,117 [ US ] in the placebo group and $ 36,008 in the SDD group ) was decreased by 42 % with the use of SDD . Clinical ly important complications of SDD were not encountered . CONCLUSIONS The use of SDD in this population of trauma patients reduced the incidence of bronchopneumonia and the total charge for antibiotics . Stay in the ICU , mechanical ventilation , and mortality rate were unchanged . Methicillin-resistant coagulase-negative staphylococci were selected by SDD in some patients and the clinical relevance of this colonization needs further evaluation Continuous enteral feeding ( CEF ) has been associated with decreased gastric acidity , thereby stimulating gastric colonization and ventilator-associated pneumonia ( VAP ) . Intermittent enteral feeding ( IEF ) could induce a temporary increase in gastric acidity and decrease the risk of VAP . We studied the influence of IEF ( 18 h/d ) and CEF ( 24 h/d ) on gastric and oropharyngeal colonization . Sixty patients were r and omized to receive either IEF or CEF , and continuous intragastric pH monitoring was performed in 50 patients . Median intragastric pH levels were similar before enteral feeding was instituted ( pH 2.5 for CEF and pH 2.4 for IEF ) , and median pH values increased slightly after institution of nutrition ( NS ) . In patients receiving IEF , median pH decreased from 3.5 to 2.2 ( p = 0.0002 ) when enteral feeding was discontinued . However , despite this , 80 % of the patients in both study groups were colonized in the stomach after 7 d in study . In addition , colonization rates of the oropharynx and trachea , the incidence of VAP , and mortality were similar in both study groups . IEF was less well tolerated than CEF . We conclude that almost all patients receiving enteral feeding are colonized in the stomach with gram-negative bacteria . IEF result ed in a slight decrease in intragastric pH without influencing rates of colonization and infection of the respiratory tract The aim of this study was to evaluate the effect of two body positions ( supine and semirecumbency ) on the dynamics of gastroesophageal reflux ( GER ) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place . Sample s of gastric contents , pharyngeal and bronchial secretions , and blood were obtained at baseline and every hour during a period of 5 h after nasogastric tube isotopic instillation of 37 megabecquerels of Tc99 m . Radioactivity counting ( RAc ) was performed using a gamma counter with correction for decay . Irrespective of the body position , all patients showed at 3 , 4 , and 5 h after the isotope instillation a significant increase in RAc of the oropharyngeal contents ( p < 0.05 , each ) , indicating GER . Although RAc values in the pharynx were higher in supine from 1 through 4 h ( p < 0.05 ) , at the end of the study ( 5 h ) the values did not differ between each position . Likewise , the slopes of the regression lines of sequential oropharyngeal RAc values were not different between each position ( 0.39 + /- 0.09 versus 0.45 + /- 0.11 , respectively ) . In contrast , RAc values in bronchial secretions were higher at 5 h in the supine position compared with baseline ( p < 0.05 ) and to semirecumbency ( p < 0.01 ) . These results strongly support that GER in mechanically ventilated patients with a nasogastric tube is a feature occurring irrespective of body position . Semirecumbent position does not protect completely from GER and subsequently from oropharyngeal colonization from gastric origin OBJECTIVE To determine if the semirecumbent position ( 45-degree angle ) decreases aspiration of gastric contents to the airways in intubated and mechanically ventilated patients . DESIGN A r and omized , two-period crossover trial . SETTING Respiratory intensive care unit . PATIENTS Nineteen patients requiring intubation and mechanical ventilation . INTERVENTIONS Patients were studied in the supine and semirecumbent positions on two separate days . MEASUREMENTS After technetium (Tc)-99 m sulphur colloid labeling of gastric contents , sequential radioactive counts in endobronchial secretions were measured at 30-minute intervals over a 5-hour period . Sample s of endobronchial secretions , gastric juice , and pharyngeal contents were obtained for qualitative bacterial cultures . RESULTS Mean radioactive counts in endobronchial secretions were higher in sample s obtained while patients were in the supine position than in those obtained while patients were in the semirecumbent position ( 4154 cpm compared with 954 cpm ; P = 0.036 ) . Moreover , the aspiration pattern was time-dependent for each position : For the supine position , radioactivity was 298 cpm at 30 min and 2592 cpm at 300 min ( P = 0.013 ) ; for the semirecumbent position , radioactivity was 103 cpm at 30 min and 216 cpm at 300 min ( P = 0.04 ) . The same microorganisms were isolated from stomach , pharynx , and endobronchial sample s in 32 % of studies done while patients were semirecumbent and in 68 % of studies done while patients were in the supine position . CONCLUSIONS We conclude that the supine position and length of time the patient is kept in this position are potential risk factors for aspiration of gastric contents . Elevating the head of the bed for patients who can tolerate the semirecumbent position may be a simple , no-cost prophylactic measure To evaluate the attributable morbidity and mortality of ventilator-associated pneumonia ( VAP ) in intensive care unit ( ICU ) patients , we conducted a prospect i ve , matched cohort study . Patients expected to be ventilated for > 48 h were prospect ively followed for the development of VAP . To determine the excess ICU stay and mortality attributable to VAP , we matched patients with VAP to patients who did not develop clinical ly suspected pneumonia . We also conducted sensitivity analyses to examine the effect of different population s , onset of pneumonia , diagnostic criteria , causative organisms , and adequacy of empiric treatment on the outcome of VAP . One hundred and seventy-seven patients developed VAP . As compared with matched patients who did not develop VAP , patients with VAP stayed in the ICU for 4.3 d ( 95 % confidence interval [ CI ] : 1.5 to 7 . 0 d ) longer and had a trend toward an increase in risk of death ( absolute risk increase : 5.8 % ; 95 % CI : -2.4 to 14.0 d ; relative risk ( RR ) increase : 32.3 % ; 95 % CI : -20.6 to 85.1 % ) . The attributable ICU length of stay was longer for medical than for surgical patients ( 6 . 5 versus 0.7 d , p < 0.004 ) , and for patients infected with " high risk " organisms as compared with " low risk " organisms ( 9.1 d versus 2.9 d ) . The attributable mortality was higher for medical patients than for surgical patients ( RR increase of 65 % versus -27.3 % , p = 0 . 04 ) . Results were similar for three different VAP diagnostic criteria . We conclude that VAP prolongs ICU length of stay and may increase the risk of death in critically ill patients . The attributable risk of VAP appears to vary with patient population and infecting organism PURPOSE To compare the performance of an in-line heat moisture exchanging filter ( HMEF ) ( Pall BB-100 ; Pall Corporation ; East Hills , NY ) to a conventional heated wire humidifier ( H-wH ) ( Marquest Medical Products Inc. , Englewood , Colo ) in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia ( VAP ) and the rate of endotracheal tube occlusion . METHODS This report describes a prospect i ve , r and omized trial of 280 consecutive trauma patients in a 20-bed trauma ICU ( TICU ) . All intubated patients not ventilated elsewhere in the medical center prior to their TICU admission were r and omized to either an in-line HMEF or a H-wH in the breathing circuit . Ventilator circuits were changed routinely every 7 days , and closed system suction catheters were changed every 3 days . HMEFs were changed every 24 h , or more frequently if necessary . A specific endotracheal tube suction and lavage protocol was not employed . Patients were dropped from the HMEF group if the filter was changed more than three times a day or the patient was placed on a regimen of ultra high-frequency ventilation . The Centers for Disease Control and Prevention ( CDC ) criteria for diagnosis of pneumonia were used ; early-onset , community-acquired pneumonia was defined if CDC criteria were met in < or =3 days , and late-onset , hospital-acquired pneumonia was defined if criteria were met in > 3 days . Laboratory and chest radiograph interpretation were blinded . RESULTS The patient ages ranged from 15 to 95 years in the HMEF group and 16 to 87 years in the H-wH group ( p = not significant ) , with a mean age of 46 years and 48 years , respectively . The male to female ratio ranged between 78 to 82%/22 to 18 % , respectively , and 55 % of all admissions were related to blunt trauma , 40 % secondary to penetrating trauma , and 5 % to major burns . There was no difference in Injury Severity Score ( ISS ) between the two groups . Moreover , there was no significant difference in mean ISS among those who did not develop pneumonia and those patients who developed either early-onset , community-acquired or late-onset , hospital-acquired pneumonia . The HMEF nosocomial VAP rate was 6 % compared to 16 % for the H-wH group ( p<0.05 ) , and total ventilator circuit costs ( per group ) were reduced . There were no differences in duration of ventilation ( mean+/-SD ) if the patient did not develop pneumonia or if the patient developed an early-onset , community-acquired or a late-onset , hospital-acquired pneumonia . Moreover , total TICU days were reduced in the HMEF group . In addition , the incidence of partial endotracheal tube occlusion was not significantly different between the H-wH and the HMEF groups . CONCLUSIONS The HMEF used in this study reduced the incidence of late-onset , hospital-acquired VAP , but not early-onset , community-acquired VAP , compared to the conventional H-wH circuit . This was associated with a significant reduction in total ICU stay . Disposable ventilator circuit costs in the HMEF group were reduced compared to the H-wH group in whom circuit changes occurred at 7-day intervals . CLINICAL IMPLICATION S The use of the HMEF is a cost-effective clinical practice associated with fewer late-onset , hospital-acquired VAPs , and should result in improved re source allocation and utilization OBJECTIVE To assess the effect on the rate of ventilator-associated pneumonia ( VAP ) of decreasing the frequency of ventilator circuit changes from three times to once per week . DESIGN Prospect i ve , r and omized trial . SETTING Medical intensive care unit ( MICU ) , a 12-bed , critical-care internal medicine unit , and neurosciences intensive care unit ( NICU ) , a 21-bed , predominantly adult neurosurgical unit , of an urban university hospital . PATIENTS All 447 patients requiring mechanical ventilation during October 1992 through June 1993 . INTERVENTION Patients were allocated r and omly on the basis of permanent medical record numbers : those with odd numbers had circuits changed three times per week , those with even numbers once per week . Intensive-care-unit surveillance was conducted in accordance with definitions and methods of the National Nosocomial Infections Surveillance System . RESULTS In the MICU , the one-change-per-week group had a VAP rate of 7.3 per 1,000 ventilator days , versus 5.9 for the three-per-week group ( P = .6 ) . In the NICU , the one-change-per-week group had a rate of 12.2 per 1,000 ventilator days , versus 12.6 for the three-per-week group ( P = .9 ) . Considering patients in both units ventilated for no more than 7 days , the one-change-per-week group had a VAP rate of 5.9 per 1,000 ventilator days , versus 9.0 per 1,000 for the three-changes-per-week group ( odds ratio [ OR ] , 0.65 ; 95 % confidence interval [ CI95 ] , 0.25 to 1.69 ) . Including patients in the two units maintained on mechanical ventilation for more than 7 days , the one-change-per-week group had a VAP rate of 13.2 per 1,000 ventilator days , versus 9.6 per 1,000 for the three-changes-per-week group ( OR , 1.37 ; CI95 , 0.71 to 2.65 ) . CONCLUSIONS Decreasing the frequency of ventilator circuit changes from three times to once per week had no adverse effect on the overall rate of VAP . Less frequent ventilator circuit changes may decrease the incidence of VAP among patients ventilated for no more than 1 week . However , the incidence of VAP may be higher among patients with once weekly circuit changes ventilated for more than 1 week One hundred fifty-three critical care patients with documented cimetidine and antacid use were prospect ively studied with serial gastric pH determinations and semiquantitative gastric fluid cultures . This study documents the abnormal gastric colonization of patients with therapeutically altered gastric acidity by hospital acquired gram negative rods ( GNR ) . Three hundred twenty-four gastric fluid cultures from 153 patients revealed 152 ( 47 % ) positive cultures for GNR , 78 ( 24 % ) sterile specimens , and 94 ( 29 % ) positive for mixed oropharyngeal flora . One hundred forty ( 59 % ) of the 236 cultures at a pH of 4 or greater were positive for GNR . In contrast , only 12 ( 14 % ) of the 88 cultures at a pH of less than 4 were positive for GNR ( p less than .001 ) . Forty-six ( 52 % ) of 88 cultures at a pH of less than 4 were sterile as compared to only 32 ( 14 % ) of 236 sterile cultures at a pH of 4 or greater ( p less than .001 ) . At low pH , cultures are predominantly sterile and at a pH of 4 or greater the flora dramatically changes to hospital acquired GNR . This artificially maintained reservoir of gram negative rods in the critically ill patient is a potential reservoir of organisms causing nosocomial bacteremia or pneumonia in this high risk population OBJECTIVE To evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients . DESIGN Prospect i ve , r and omized , concurrent trial . SETTING Multidisciplinary intensive care unit ( ICU ) in a 1,800-bed university hospital . PATIENTS Consecutive patients ( n = 660 ) who were likely to require mechanical ventilation for at least 48 hrs were r and omized to one of three groups : conventional antibiotic regimen ( control group A ) ; oral and enteral ofloxacin-amphotericin B ( group B ) ; and oral and enteral polymyxin E-tobramycin-amphotericin B ( group C ) . Both treatment groups received systemic antibiotics for 4 days ( ofloxacin in group B and cefotaxime in group C ) . INTERVENTIONS Patients were r and omized to receive st and ard treatment ( control group A , n = 220 ) , selective decontamination regimen B ( group B , n = 220 ) , and selective decontamination regimen C ( group C , n = 220 ) . After early deaths and exclusions from the study , 185 controls ( group A ) and 193 ( group B)/200 ( group C ) selective decontamination regimen patients were available for analysis . MEASUREMENTS AND MAIN RESULTS Measurements included colonization and primary / secondary infection rate , ICU mortality rate , emergence of antibiotic resistance , length of ICU stay , and antimicrobial agent costs . The study duration was 19 months . The patient groups were fully comparable for age , diagnostic category , and severity of illness . One third of patients in each group suffered a nosocomial infection at the time of admission . There was a significant difference between treatment group B and control group A in the number of infected patients ( odds ratio of 0.42 , 95 % confidence interval of 0.27 to 0.64 ) , secondary lower respiratory tract infection ( odds ratio of 0.47 , 95 % confidence interval of 0.26 to 0.82 ) , and urinary tract infection ( odds ratio of 0.47 , 95 % confidence interval of 0.27 to 0.81 ) . Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A ( odds ratio of 1.22 , 95 % confidence interval 0.72 to 2.08 ) . Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups . ICU mortality rate was almost identical ( group A 16.8 % , group B 17.6 % , and group C 15.5 % ) and was not significantly related to primary or secondary infection . Increased antimicrobial resistance was recorded in both treatment groups : tobramycin-resistant enterobacteriaceae ( group C 48 % vs. group A 14 % , p < .01 ) , ofloxacin-resistant enterobacteriaceae ( group B 50 % vs. group A 11 % , p < .02 ) , ofloxacin-resistant nonfermenters ( group B 81 % vs. group A 52 % , p < .02 ) , and methicillin-resistant Staphylococcus aureus ( group C 83 % vs. group A 55 % , p < .05 ) . Antimicrobial agent costs were comparable in control and group C patients ; one third less was spent for group B patients . CONCLUSIONS In cases of high colonization and infection rates at the time of ICU admission , the preventive benefit of selective decontamination is highly debatable . Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental , colonizing , and infecting bacteria . The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous . No beneficial effect on survival is observed . Moreover , selective decontamination adds substantially to the cost of ICU care In comatose patients admitted to an ICU , particularly those with head injury , the incidence of early onset pneumonia is exceedingly high . We performed an open , prospect i ve , r and omized , and controlled clinical trial aim ing at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation . One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study ( n = 50 ) received cefuroxime intravenously ( two 1,500-mg doses 12 h apart after intubation ) ( the cefuroxime group ) and 50 patients not receiving cefuroxime formed the control group . In the former group patients did not receive any other antibiotics before the end-point determination , whereas in the latter , 17 patients received prophylactic antibiotics as prescribed by the attending physician . The global incidence of microbiologically confirmed pneumonia was 37 % ( n = 37 ) ; 12 ( 24 % ) belonged to the cefuroxime group , and 25 ( 50 % ) belonged to the control group ( p = 0.007 ) . Early-onset pneumonia accounted for 70 % of all the pneumonia episodes ( n = 26 ) , eight ( 67 % ) belonging to the cefuroxime group , and 18 ( 72 % ) belonging to the control group ( p = 0.02 ) . In the control group , four of 17 ( 23 % ) patients receiving prior antibiotics developed pneumonia , whereas 21 of 33 ( 64 % ) patients who did not receive antibiotics developed pneumonia ( p = 0.016 ) . The multivariate analysis revealed that the duration of mechanical ventilation ( per each day ) was an independent risk factor significantly associated to the development of pneumonia . Furthermore , the use of cefuroxime and /or prior antibiotics in the control group , before the pneumonia episode , had a protective effect against its development . No differences were found with regard to mortality and morbidity when comparing the study population with the control group . Nevertheless , when comparing patients with pneumonia ( from both study and control groups ) with those without it , there was a decrease in total hospital stay ( 35 + /- 13 versus 25 + /- 14 d , p = 0.048 ) and ICU stay ( 20 + /- 11 versus 11 + /- 7 d , p = 0.001 ) . The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia STUDY OBJECTIVES To determine whether the application of continuous aspiration of subglottic secretions ( CASS ) is associated with a decreased incidence of ventilator-associated pneumonia ( VAP ) . DESIGN Prospect i ve clinical trial . SETTING Cardiothoracic ICU ( CTICU ) of Barnes-Jewish Hospital , St. Louis , a university-affiliated teaching hospital . PATIENTS Three hundred forty-three patients undergoing cardiac surgery and requiring mechanical ventilation in the CTICU . INTERVENTIONS Patients were assigned to receive either CASS , using a specially design ed endotracheal tube ( Hi-Lo Evac ; Mallinckrodt Inc ; Athlone , Irel and ) , or routine postoperative medical care without CASS . RESULTS One hundred sixty patients were assigned to receive CASS , and 183 were assigned to receive routine postoperative medical care without CASS . The two groups were similar at the time of r and omization with regard to demographic characteristics , surgical procedures performed , and severity of illness . Risk factors for the development of VAP were also similar during the study period for both treatment groups . VAP was seen in 8 patients ( 5.0 % ) receiving CASS and in 15 patients ( 8 . 2 % ) receiving routine postoperative medical care without CASS ( relative risk , 0.61 % ; 95 % confidence interval , 0.27 to 1.40 ; p = 0 . 238 ) . Episodes of VAP occurred statistically later among patients receiving CASS ( [ mean + /- SD ] 5.6 + /- 2.3 days ) than among patients who did not receive CASS ( 2.9 + /- 1.2 days ) ; ( p = 0.006 ) . No statistically significant differences for hospital mortality , overall duration of mechanical ventilation , lengths of stay in the hospital or CTICU , or acquired organ system derangements were found between the two treatment groups . No complications related to CASS were observed in the intervention group . CONCLUSIONS Our findings suggest that CASS can be safely administered to patients undergoing cardiac surgery . The occurrence of VAP can be significantly delayed among patients undergoing cardiac surgery using this simple-to-apply technique OBJECTIVE To evaluate the effect of acidified enteral feeds on gastric colonization in critically ill patients compared with a st and ard feeding formula . DESIGN R and omized , double-blind , multicenter trial . SETTING Eight mixed intensive care units at tertiary care hospitals . PATIENTS We recruited mechanically ventilated critically ill patients expected to remain ventilated for > 48 hrs . We excluded patients with gastrointestinal bleeding , acidemia , and renal failure requiring dialysis . We enrolled 120 patients ; 38 % were female , age ( mean + /- SD ) was 57.6+/-19.3 yrs , and Acute Physiology and Chronic Health Evaluation II score ( mean + /- SD ) was 21.6+/-7.6 . INTERVENTIONS Vital High Nitrogen ( Abbott Laboratories , Ross Products Division , Columbus , OH ) was used as the st and ard feeding formula for the control group ( pH = 6.5 ) . Hydrochloric acid was added to Vital High Nitrogen to achieve a pH of 3.5 in the experimental group . MEASUREMENTS AND MAIN RESULTS The main outcome measure was gastric colonization . Secondary outcomes included gastric pH , pneumonia , and mortality . The mean gastric pH in patients receiving acid feeds was lower ( pH = 3.3 ) compared with controls ( pH = 4.6 ; p<.05 ) . One patient ( 2 % ) on acid feeds was colonized in the stomach with pathogenic bacteria , compared with 20 patients ( 43 % ) in the control group ( p<.001 ) . There was no difference in the incidence of pneumonia ( 6.1 % in the acid feeds group vs. 15 % in the control group ; p = .19 ) . Overall , there were 15 deaths in the acid feeds group and seven in the control group ( p = .10 ) ; four patients in the acid feeds group and three in the control group died during the study period ( p not significant ) . CONCLUSIONS Acidified enteral feeds preserve gastric acidity and substantially reduce gastric colonization in critically ill patients . Larger studies are needed to examine its effect on ventilator-associated pneumonia and mortality Chronic microaspiration through a tracheal cuff is the main culprit in the penetration and colonization of the lower respiratory tract . A total of 145 patients intubated for more than 3 days were r and omly assigned to a double nosocomial pneumonia ( NP ) prevention : 1-Prevention of aspiration by hourly subglottic secretion drainage ( SSD ) with a specific endotracheal tube ( HI-LO Evac tube , Mallinckrodt ) ; 2-Prevention of gastric colonization using either sucralfate or antacids . Four r and om groups were defined , similar in age and severity of illness . Subglottic secretion drainage treatment was associated with : a ) a twice lower incidence of NP ( no-SSD : 29.1 % , SSD : 13 % ) ; b ) a prolonged time of onset of NP ( no-SSD : 8.3±5 days , SSD : 16.2±11 days ) ; c ) a decrease in the colonization rate from admission to end-point day in tracheal aspirates ( no-SSD:+21.3 % , SSD:+6.6 % ) and in subglottic secretions ( no-SSD:+33.4 % , SSD:+2.1 % ) . Sucralfate was not associated with a significantly lower incidence of NP ( antacids : 23.6 % , sucralfate : 17.8 % ) , but with a lower increase in the colonization rate in subglottic and gastric aspirates , from admission to end-point day OBJECTIVES To identify factors associated with the development of ventilator-associated pneumonia ( VAP ) and to examine the incidence of VAP in different intensive care unit ( ICU ) population s. DESIGN An inception cohort study . SETTING Barnes Hospital , St Louis , Mo , an academic tertiary care center . PATIENTS OR OTHER PARTICIPANTS A total of 277 consecutive patients required mechanical ventilation for longer than 24 hours from a medical ICU ( 75 patients ) , surgical ICU ( 100 patients ) , or cardiothoracic ICU ( 102 patients ) . INTERVENTIONS Prospect i ve patient surveillance and data collection . MAIN OUTCOME MEASURES Ventilator-associated pneumonia and ICU mortality . RESULTS Ventilator-associated pneumonia occurred in 43 patients ( 15.5 % ) . Stepwise logistic regression analysis identified four factors to be independently associated with VAP ( P < .05 ) : an organ system failure index of 3 or greater ( adjusted odds ratio [ AOR ] = 10.2 ; 95 % confidence interval [ CI ] , 4.5 to 23 ; P < .001 ) ; patient age of 60 years or older ( AOR = 5.1 ; 95 % CI , 1.9 to 14.1 ; P = .002 ) ; prior administration of antibiotics ( AOR = 3.1 ; 95 % CI , 1.4 to 6.9 ; P = .004 ) ; and supine head positioning during the first 24 hours of mechanical ventilation ( AOR = 2.9 ; 95 % CI , 1.3 to 6.8 ; P = .013 ) . Ventilator-associated pneumonia occurred more often in cardiothoracic patients ( 21.6 % ) compared with medical patients ( 9.3 % ) ( P = .03 ) . Patients with VAP also had a higher mortality ( 37.2 % ) than those without VAP ( 8.5 % ) ( P < .001 ) . An organ system failure index of 3 or greater ( AOR = 16.1 ; 95 % CI , 6.1 to 42 ; P < .001 ) , a premorbid lifestyle score of 2 or greater ( AOR = 3.1 ; 95 % CI , 1.3 to 7.3 ; P = .012 ) , and supine head positioning during the first 24 hours of mechanical ventilation ( AOR = 3.1 ; 95 % CI , 1.2 to 7.8 ; P = .016 ) were independently associated with mortality . CONCLUSIONS These data suggest potential interventions that might affect the incidence of VAP or outcome associated with VAP . Additionally , they indicate that different ICU population s may have different incidences of VAP |
11,261 | 30,602,377 | However , there was no significant improvement in other domains of cognition .
Conclusions NIBS has a positive effect on improving global cognitive function and verbal fluency .
At the same time , it has a small positive effect on improving executive function . | Background To prevent and control dementia , many scholars have focused on the transition stage between normal ageing and dementia , mild cognitive impairment ( MCI ) which is a key interventional target for dementia .
Studies have shown that non-invasive brain stimulation ( NIBS ) is beneficial to improve cognitive function of MCI patients .
However , whether NIBS is conducive to the protection of cognitive ability in MCI patients remains unknown due to limited evidence .
The aim of the study was to systematic ally evaluate the modulation effect of NIBS on cognitive function ( global cognitive ability and specific domains of cognition ) in patients with MCI . | ABSTRACT Memory loss is one of the first symptoms of typical Alzheimer 's disease ( AD ) , for which there are no effective therapies available . The precuneus ( PC ) has been recently emphasized as a key area for the memory impairment observed in early AD , likely due to disconnection mechanisms within large‐scale networks such as the default mode network ( DMN ) . Using a multimodal approach we investigated in a two‐week , r and omized , sham‐controlled , double‐blinded trial the effects of high‐frequency repetitive transcranial magnetic stimulation ( rTMS ) of the PC on cognition , as measured by the Alzheimer Disease Cooperative Study Pre clinical Alzheimer Cognitive Composite in 14 patients with early AD ( 7 females ) . TMS combined with electroencephalography ( TMS‐EEG ) was used to detect changes in brain connectivity . We found that rTMS of the PC induced a selective improvement in episodic memory , but not in other cognitive domains . Analysis of TMS‐EEG signal revealed an increase of neural activity in patients ' PC , an enhancement of brain oscillations in the beta b and and a modification of functional connections between the PC and medial frontal areas within the DMN . Our findings show that high‐frequency rTMS of the PC is a promising , non‐invasive treatment for memory dysfunction in patients at early stages of AD . This clinical improvement is accompanied by modulation of brain connectivity , consistently with the pathophysiological model of brain disconnection in AD . HighlightsThe precuneus is a key area for memory impairment in Alzheimer ’s disease (AD).We investigated the effects of precuneus‐rTMS on memory in patients with early AD.Precuneus‐rTMS induced a selective improvement in episodic memory . Precuneus‐rTMS enhance precuneus activity and connectivity with frontal areas .Precuneus‐rTMS is a promising treatment for memory dysfunction in early AD patients OBJECTIVE To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of major depressive disorder ( MDD ) . PARTICIPANTS Participants included a group of 17 expert clinicians and research ers with expertise in the clinical application of rTMS , representing both the National Network of Depression Centers ( NNDC ) rTMS Task Group and the American Psychiatric Association Council on Research ( APA CoR ) Task Force on Novel Biomarkers and Treatments . EVIDENCE The consensus statement is based on a review of extensive literature from 2 data bases ( OvidSP MEDLINE and PsycINFO ) search ed from 1990 through 2016 . The search terms included variants of major depressive disorder and transcranial magnetic stimulation . The results were limited to articles written in English that focused on adult population s. Of the approximately 1,500 retrieved studies , a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice setting s. CONSENSUS PROCESS In cases in which the research evidence was equivocal or unclear , a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as " expert opinion . " CONCLUSIONS Multiple r and omized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy . These consensus recommendations , developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments , provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD Episodic memory displays the largest degree of age-related decline , a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer 's disease . Previous studies have shown that the left lateral prefrontal cortex ( PFC ) contributes to the encoding of episodic memories along the life span . The aim of this r and omized , double-blind , placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation ( tDCS ) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals . Older adults learned a list of words while receiving anodal or placebo ( sham ) tDCS . Memory recall was tested 48 hours and 1 month later . The results showed that anodal tDCS strengthened episodic memories , an effect indicated by enhanced delayed recall ( 48 hours ) compared to placebo stimulation ( Cohen 's d effect size = 1.01 ) . The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design -specific neurorehabilitation protocol s targeted to conditions that affect episodic memory such as mild cognitive impairment Objective : Given the limited effectiveness of pharmacological treatments , non-pharmacological interventions to treat Alzheimer 's disease ( AD ) have gained attention in recent years . The aim of the present study is to investigate the effects of anodal tDCS ( AtDCS ) combined with memory training on face-name associations in an AD patient sample . Methods : Thirty six AD patients were r and omly assigned to one of three study groups : Group 1 , AtDCS plus individualized computerized memory training ; Group 2 , placebo tDCS plus individualized computerized memory training ; Group 3 , AtDCS plus motor training . Results : A general improvement in performance was observed after 2 weeks of memory training . Both the anodal tDCS plus individualized computerized memory training and the placebo tDCS plus individualized computerized memory training groups had significantly improved performances at 2 weeks compared with the AtDCS plus motor training group . Conclusion : Our findings suggest a beneficial effect of individualized memory rehabilitation in AD patients Background : The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation ( tDCS ) in the neurorehabilitation of Alzheimer ’s disease ( AD ) . Methods : Thirty-four AD patients were r and omly assigned to three groups : anodal , cathodal , and sham tDCS . Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA , daily for 10 days . Each patient was su bmi tted to the following psychometric assessment s : mini-mental state examination ( MMSE ) and Wechsler adult intelligence scale-third edition at base line , at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions . Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session . Results : Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS . Post hoc comparisons showed that both anodal and cathodal tDCS ( ctDCS ) improved MMSE in contrast to sham tDCS . Whereas , this was only true for ctDCS in the performance IQ . Remarkably , tDCS also reduced the P300 latency , but had no effect on motor cortex excitability . Conclusion : Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency , which is known to be pathologically increased in AD Transcranial magnetic stimulation ( TMS ) is a noninvasive brain stimulation technique with potential to improve memory . Mild cognitive impairment ( MCI ) , which still lacks a specific therapy , is a clinical syndrome associated with increased risk of dementia . This study aims to assess the effects of high-frequency repetitive TMS ( HF rTMS ) on everyday memory of the elderly with MCI . We conducted a double-blinded r and omized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) . Thirty-four elderly out patients meeting Petersen 's MCI criteria were r and omly assigned to receive 10 sessions of either active TMS or sham , 10 Hz rTMS at 110 % of motor threshold , 2,000 pulses per session . Neuropsychological assessment at baseline , after the last session ( 10th ) and at one-month follow-up , was applied . ANOVA on the primary efficacy measure , the Rivermead Behavioural Memory Test , revealed a significant group-by-time interaction ( p = 0.05 ) , favoring the active group . The improvement was kept after one month . Other neuropsychological tests were heterogeneous . rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions . These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration Remembering the location of objects , an integral part of everyday life , is known to decline with advancing age and early in the course of neurodegenerative dementia . Here , we aim ed to test if object-location learning and its retention could be modified by noninvasive brain stimulation . In a group of 20 elderly ( mean age 62.1 years ) right-h and ed individuals , we applied transcranial direct current stimulation ( tDCS ; 20 minutes , 1 mA ) over the right temporoparietal cortex , while subjects acquired the correct position of buildings on a street map using an associative learning paradigm . Each subject participated in a r and omized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation , in a double-blind design with 2 parallel versions of the task . Outcome measures were learning success at the end of each session , and immediate as well as delayed ( 1 week ) free recall . We found that subjects performed comparably in the learning task in the 2 conditions , but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation . In conclusion , retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation , a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation ( rTMS ) , applied bilaterally over the dorsolateral prefrontal cortex ( DLPFC ) , on cognitive function and cortical excitability of patients with Alzheimer 's disease ( AD ) . Forty-five AD patients were r and omly classified into three groups . The first two groups received real rTMS over the DLPFC ( 20 and 1 Hz , respectively ) while the third group received sham stimulation . All patients received one session daily for five consecutive days . In each session , rTMS was applied first over the right DLPFC , immediately followed by rTMS over the left DLPFC . Mini Mental State Examination ( MMSE ) , Instrumental Daily Living Activity ( IADL ) scale and the Geriatric Depression Scale ( GDS ) were assessed before , after the last ( fifth ) session , and then followed up at 1 and 3 months . Neurophysiological evaluations included resting and active motor threshold ( rMT and aMT ) , and the duration of transcallosal inhibition ( TI ) before and after the end of the treatment sessions . At base line assessment there were no significant differences between groups in any of the rating scales . The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales ( MMSE , IADL , and GDS ) and at all time points after treatment . Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration . These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD . This improvement was maintained for 3 months . High frequency rTMS may be a useful addition to therapy for the treatment of AD The long pre clinical phase of Alzheimer 's disease provides opportunities for potential disease‐modifying interventions in prodromal stages such as mild cognitive impairment ( MCI ) . Anodal transcranial direct current stimulation ( anodal‐tDCS ) , with its potential to enhance neuroplasticity , may allow improving cognition in MCI The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating INTRODUCTION Repetitive transcranial magnetic stimulation ( rTMS ) is a noninvasive tool for modulating cortical activity . OBJECTIVES In this pilot study , we evaluated the effects of high frequency rTMS applied over the right inferior frontal gyrus ( IFG ) on cognitive functions in patients with amnestic mild cognitive impairment ( MCI ) or incipient dementia due to Alzheimer 's disease ( AD ) . METHODS Ten patients ( 6 men ; 4 women , mean age of 72 ± 8 years ; MMSE 23 ± 3.56 ) were enrolled in a r and omized , placebo-controlled study with a crossover design . All participants received 2 sessions of 10 Hz rTMS over the non-dominant right hemisphere in r and om order : IFG ( active stimulation site ) and vertex ( control stimulation site ) . Intensities were adjusted to 90 % of resting motor threshold . A total of 2250 pulses were applied in a session . The Trail Making Test ( TMT ) , the Stroop test , and the complex visual scene encoding task ( CVSET ) were administered before and immediately after each session . The Wilcoxon paired test was used for data analysis . RESULTS Stimulation applied over the IFG induced improvement in the TMT parts A ( p = 0.037 ) and B ( p = 0.049 ) . No significant changes were found in the Stroop test or the CVSET after the IFG stimulation . We observed no significant cognitive aftereffects of rTMS applied over the vertex . CONCLUSIONS High frequency rTMS of the right IFG induced significant improvement of attention and psychomotor speed in patients with MCI/mild dementia due to AD . This pilot study is part of a more complex protocol and ongoing research Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions . The presence of apathy with Mild Cognitive Impairment ( MCI ) is linked with heightened rates of conversion to Alzheimer 's disease . Improving apathy may slow the neurodegenerative process . The objective was to establish the efficacy of repetitive transcranial magnetic stimulation ( rTMS ) in improving apathy in older adults with MCI . An 8-week , double-blind , r and omized , sham-controlled cross-over study was conducted in nine subjects ( 66 ± 9 years ) with apathy and MCI . Subjects were r and omized to rTMS or sham treatment ( 5 days/week ) for 2 weeks following which they underwent a 4-week treatment-free period . Subjects then crossed-over to receive the other treatment for 2 weeks . The primary ( apathy ( AES-C ) ) and secondary ( cognition ( 3MS & MMSE ) , executive function ( TMT-A & TMT-B ) , and clinical global impression ( CGI ) ) outcomes were assessed at baseline , 2 , 6 , and 8 weeks . After adjusting for baseline , there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks . There was significantly greater improvement in 3MS , MMSE , TMT-A , and CGI-I with rTMS compared to the sham treatment . This study establishes that rTMS is efficacious in improving apathy in subjects with MCI |
11,262 | 30,762,623 | These studies suggest that any additive ergogenic creatine effects on upper and /or lower body strength , functional capacity , and lean mass in an older population would require a continuous and daily low-dose creatine supplementation combined with at least 12 weeks of resistance training .
The limited data suggested no additive effects of creatine over exercise alone on indices of mental health .
The beneficial effects of creatine supplementation are more consistent in older women than in men .
Conclusions : Creatine monohydrate is safe to use in older adults . | Background and Purpose : The role of creatine supplementation in young athletes and bodybuilders is well established including ergogenic properties of muscular hypertrophy , strength , power , and endurance .
Whether the benefits of creatine supplementation translate to an aging population with moderate training stimulus remains unclear especially in regard to gender , creatine dose , and duration .
This systematic review assessed whether creatine supplementation combined with exercise results in additive improvements in indices of skeletal muscle , bone , and mental health over exercise alone in healthy older adults . | Abstract Background Human ageing is a process characterized by loss of muscle mass , strength , and bone mass . We aim ed to examine the efficacy of low‐dose creatine supplementation associated with resistance training on lean mass , strength , and bone mass in the elderly . Methods This was a 12‐week , parallel‐group , double‐blind , r and omized , placebo‐controlled trial . The individuals were r and omly allocated into one of the following groups : placebo plus resistance training ( PL + RT ) and creatine supplementation plus resistance training ( CR + RT ) . The participants were assessed at baseline and after 12 weeks . The primary outcomes were lean mass and strength , assessed by dual energy X‐ray absorptiometry ( DXA ) and ten‐repetition maximal tests ( 10 RM ) , respectively . Secondary outcomes included the lumbar spine , right and left femoral neck , both femur and whole body bone mineral density ( BMD ) , and whole body bone mineral content ( BMC ) , assessed by DXA . Results The CR + RT group had superior gains in lean mass when compared with the PL + RT group ( P = 0.02 ) . Changes in the 10 RM tests in bench press and leg press exercises , body composition , BMD , and BMC of all assessed sites did not significantly differ between the groups ( P > 0.05 ) . Conclusions Twelve weeks of low‐dose creatine supplementation associated with resistance training result ed in increases in lean mass in the elderly Purpose To assess the effects of creatine supplementation , associated or not with strength training , upon emotional and cognitive measures in older woman . Methods This is a 24-week , parallel-group , double-blind , r and omized , placebo-controlled trial . The individuals were r and omly allocated into one of the following groups ( n=14 each ) : 1 ) placebo , 2 ) creatine supplementation , 3 ) placebo associated with strength training or 4 ) creatine supplementation associated with strength training . According to their allocation , the participants were given creatine ( 4 x 5 g/d for 5 days followed by 5 g/d ) or placebo ( dextrose at the same dosage ) and were strength trained or not . Cognitive function , assessed by a comprehensive battery of tests involving memory , selective attention , and inhibitory control , and emotional measures , assessed by the Geriatric Depression Scale , were evaluated at baseline , after 12 and 24 weeks of the intervention . Muscle strength and food intake were evaluated at baseline and after 24 weeks . Results After the 24-week intervention , both training groups ( ingesting creatine supplementation and placebo ) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group ( p = 0.001 and p = 0.01 , respectively ) and the non-trained creatine group ( p < 0.001 for both comparison ) . However , no significant differences were observed between the non-trained placebo and creatine ( p = 0.60 ) groups , or between the trained placebo and creatine groups ( p = 0.83 ) . Both trained groups , irrespective of creatine supplementation , had better muscle strength performance than the non-trained groups . Neither strength training nor creatine supplementation altered any parameter of cognitive performance . Food intake remained unchanged . Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals . In addition , strength training per se improved emotional state and muscle strength , but not cognition , with no additive effects of creatine supplementation . Trial Registration Clinical trials.gov Abstract Purpose The present study evaluated the effects of creatine monohydrate ( CrM ) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program . Methods In a double-blind , r and omized trial , 20 males aged between 55 and 70 years were r and omly assigned to consume either CrM-carbohydrate ( CHO ) [ 20 g days−1 CrM + 5 g days−1 CHO × 7 days , then 0.1 g kg−1 CrM + 5 g CHO on training days ( average dosage of ~8.8 g ) ] or placebo CHO ( 20 g days−1 CHO × 7 days , then 5 g CHO on training days ) while participating in a high intensity resistance training program [ 3 sets × 10 repetitions at 75 % of 1 repetition maximum ( 1RM ) ] , 3 days weeks−1 for 12 weeks . Following the initial 7-day “ loading ” phase , participants were instructed to ingest their supplement within 60 min post-exercise . Body composition and muscle strength measurements , blood collection and vastus lateralis muscle biopsy were completed at 0 , 4 , 8 and 12 weeks of the supplement and resistance training program . Results A significant time effect was observed for 1RM bench press ( p = 0.016 ) , leg press ( p = 0.012 ) , body mass ( p = 0.03 ) , fat-free mass ( p = 0.005 ) and total myofibrillar protein ( p = 0.005 ) . A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training ( p = 0.08 ) . No supplement interaction effects were observed . Conclusion Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males PURPOSE To determine whether low-dose creatine and protein supplementation during resistance training ( RT ; 3 d x wk(-1 ) ; 10 wk ) in older men ( 59 - 77 yr ) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites ( formaldehyde ) . METHODS Older men were r and omized ( double-blind ) to receive 0.1 g x kg(-1 ) creatine + 0.3 g x kg(-1 ) protein ( CP ; n = 10 ) , creatine ( C ; n = 13 ) , or placebo ( PLA ; n = 12 ) on training days . Measurements before and after RT included lean tissue mass ( air-displacement plethysmography ) , muscle thickness ( ultrasound ) of elbow , knee , and ankle flexors and extensors , leg and bench press strength , and urinary indicators of cytotoxicity ( formaldehyde ) , myofibrillar protein degradation [ 3-methylhistidine ( 3-MH ) ] , and bone resorption [ cross-linked N-telopeptides of type I collagen ( NTx ) ] . RESULTS Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA ( P < 0.05 ) . Subjects who received CP increased lean tissue mass ( + 5.6 % ) more than C ( + 2.2 % ) or PLA ( + 1.0 % ; P < 0.05 ) and increased bench press strength ( + 25 % ) to a greater extent than C and PLA combined ( + 12.5 % ; P < 0.05 ) . CP and C did not differ from PLA for changes in formaldehyde production ( + 24 % each ) . Subjects receiving creatine ( C and CP ) experienced a decrease in 3-MH by 40 % compared with an increase of 29 % for PLA ( P < 0.05 ) and a reduction in NTx ( -27 % ) versus PLA ( + 13 % ; P = 0.05 ) . CONCLUSIONS Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength . Low-dose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production Objectives Creatine and protein supplementation can enhance the training outcomes of young subjects , but it is not clear if there are benefits for older individuals . Therefore , the purpose of this study was to determine the effects of creatine and protein supplementation on strength gains following a traditional resistance training program for middle-aged and older men . Design , Setting , Participants This study assessed changes in strength of men aged 48–72 years following 14 weeks of resistance training supplemented with creatine and /or protein . A double-blind , r and omized , placebo-controlled design placed 42 males into one of four groups : Resistance Trained Placebo ( RTP , n=10 ) ; Resistance Trained Creatine ( RTCr , 5 g Cr , n=10 ) ; Resistance Trained Protein ( RTPr , 35 g whey Pr , n=11 ) ; or Resistance Trained Creatine and Protein ( RTCrPr , 5 g Cr and 35 g Pr , n=11).InterventionAll groups trained 3 days per week for 14 weeks . The resistance training program was based on progressive overload . Training loads corresponded to 80 % 1RM ( one repetition maximum strength ) , 3 sets of 8 repetitions for the following exercises : knee extension/knee flexion ; bicep curl/tricep extension ; military press ; lat pull down ; seated leg press ; and bench press . Measurements 1 RM for each exercise and measures of lean body mass were assessed prior to and following the 14 week program . Results Each group significantly ( p<0.05 ) increased strength and lean body mass , however , there were no significant group effects or group X trial interactions . Conclusion Resistance training in middle-aged and older men significantly increased muscular strength and added muscle mass with no additional benefits from creatine and /or protein supplementation This study examined the effects of long-term creatine supplementation combined with resistance training ( RT ) on the one-repetition maximum ( 1RM ) strength , motor functional performance ( e.g. , 30-s chair st and , arm curl , and getting up from lying on the floor tests ) and body composition ( e.g. , fat-free mass , muscle mass , and % body fat using DEXA scans ) in older women . Eighteen healthy women ( 64.9 ± 5.0 years ) were r and omly assigned in a double-blind fashion to either a creatine ( CR , N = 9 ) or placebo ( PL , N = 9 ) group . Both groups underwent a 12-week RT program ( 3 days week−1 ) , consuming an equivalent amount of either creatine ( 5.0 g day−1 ) or placebo ( maltodextrin ) . After 12 week , the CR group experienced a greater ( P < 0.05 ) increase ( Δ% ) in training volume ( + 164.2 ) , and 1RM bench press ( + 5.1 ) , knee extension ( + 3.9 ) and biceps curl ( + 8.8 ) performance than the PL group . Furthermore , CR group gained significantly more fat-free mass ( + 3.2 ) and muscle mass ( + 2.8 ) and were more efficient in performing submaximal-strength functional tests than the PL group . No changes ( P > 0.05 ) in body mass or % body fat were observed from pre- to post-test in either group . These results indicate that long-term creatine supplementation combined with RT improves the ability to perform submaximal-strength functional tasks and promotes a greater increase in maximal strength , fat-free mass and muscle mass in older women Aging is associated with lower muscle mass and an increase in body fat . We examined whether creatine monohydrate ( CrM ) and conjugated linoleic acid ( CLA ) could enhance strength gains and improve body composition ( i.e. , increase fat-free mass ( FFM ) ; decrease body fat ) following resistance exercise training in older adults ( > 65 y ) . Men ( N = 19 ) and women ( N = 20 ) completed six months of resistance exercise training with CrM (5g/d)+CLA ( 6g/d ) or placebo with r and omized , double blind , allocation . Outcomes included : strength and muscular endurance , functional tasks , body composition ( DEXA scan ) , blood tests ( lipids , liver function , CK , glucose , systemic inflammation markers ( IL-6 , C-reactive protein ) ) , urinary markers of compliance ( creatine/creatinine ) , oxidative stress ( 8-OH-2dG , 8-isoP ) and bone resorption ( Ν-telopeptides ) . Exercise training improved all measurements of functional capacity ( P<0.05 ) and strength ( P<0.001 ) , with greater improvement for the CrM+CLA group in most measurements of muscular endurance , isokinetic knee extension strength , FFM , and lower fat mass ( P<0.05 ) . Plasma creatinine ( P<0.05 ) , but not creatinine clearance , increased for CrM+CLA , with no changes in serum CK activity or liver function tests . Together , this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period . Trial Registration . Clinical Trials.gov effect of oral creatine supplementation ( CR ; 5 g/day ) in conjunction with exercise training on physical fitness was investigated in men between 55 and 75 yr of age ( n = 46 ) . A double-blind r and omized placebo-controlled ( PL ) trial was performed over a 6-mo period . Furthermore , a subgroup ( n = 20 ) completed a 1-yr follow-up . The training program consisted of cardiorespiratory endurance training as well as moderate resistance training ( 2 - 3 sessions/wk ) . Endurance capacity was evaluated during a maximal incremental bicycle ergometer test , maximal isometric strength of the knee-extensor muscles was assessed by an isokinetic dynamometer , and body composition was assessed by hydrostatic weighing . Furthermore , in a subgroup ( PL : n = 13 ; CR : n = 12 ) biopsies were taken from m. vastus lateralis to determine total creatine ( TCr ) content . In PL , 6 mo of training increased peak oxygen uptake rate ( + 16 % ; P < 0.05 ) . Fat-free mass slightly increased ( + 0.3 kg ; P < 0.05 ) , whereas percent body fat slightly decreased ( -1.2 % ; P < 0.05 ) . The training intervention did not significantly change either maximal isometric strength or body weight . The responses were independent of CR . Still , compared with PL , TCr was increased by approximately 5 % in CR , and this increase was closely correlated with initial muscle creatine content ( r = -0.78 ; P < 0.05 ) . After a 1-yr follow-up , muscle TCr was not higher in CR than in PL . Furthermore , the other measurements were not affected by CR . It is concluded that long-term creatine intake ( 5 g/day ) in conjunction with exercise training does not beneficially impact physical fitness in men between 55 and 75 yr of age PURPOSE Our primary purpose was to determine the effect of 12 months of creatine ( Cr ) supplementation during a supervised resistance training program on properties of bone in postmenopausal women . METHODS Participants were r and omized ( double-blind ) into two groups : resistance training ( 3 d·wk ) and Cr supplementation ( 0.1 g·kg·d ) or resistance training and placebo ( Pl ) . Our primary outcome measures were lumbar spine and femoral neck bone mineral density ( BMD ) . Secondary outcome measures were total hip and whole-body BMD , bone geometric properties at the hip , speed of sound at the distal radius and tibia , whole-body lean tissue mass , muscle thickness , and bench press and hack squat strength . Forty-seven women ( 57 ( SD , 6 ) yr ; Cr , n = 23 ; Pl , n = 24 ) were r and omized , with 33 analyzed after 12 months ( Cr , n = 15 ; Pl , n = 18 ) . RESULTS Cr attenuated the rate of femoral neck BMD loss ( -1.2 % ; absolute change ( 95 % confidence interval ) , -0.01 ( -0.025 to 0.005 ) g·cm ) compared with Pl ( -3.9 % ; -0.03 ( -0.044 to -0.017 ) g·cm ; P < 0.05 ) and also increased femoral shaft subperiosteal width , a predictor of bone bending strength ( Cr , 0.04 ( -0.09 to 0.16 ) cm ) ; Pl , -0.12 ( -0.23 to -0.01 ) cm ; P < 0.05 ) . Cr increased relative bench press strength more than Pl ( 64 % vs 34 % ; P < 0.05 ) . There were no differences between groups for other outcome measures . There were no differences between groups for reports of serum liver enzyme abnormalities , and creatinine clearance was normal for Cr participants throughout the intervention . CONCLUSIONS Twelve months of Cr supplementation during a resistance training program preserves femoral neck BMD and increases femoral shaft superiosteal width , a predictor of bone bending strength , in postmenopausal women Our purpose was to determine the effects of creatine supplementation combined with resistance training on bone mineral content and density in older men . Twenty-nine older men ( age 71 y ) were r and omized ( double blind ) to receive creatine ( 0.3 g/kg creatine for 5 d and 0.07 g/kg thereafter ) or placebo while participating in resistance training ( 12 weeks ) . Bone mineral content and density were determined by dual energy X-ray absorptiometry before and after training . There was a time main effect for whole-body and leg bone mineral density ( p < or = 0.05 ) with these measures increasing by approximately 0.5 % , and 1 % , respectively in the combined groups . There was a group by time interaction for arms bone mineral content , with the group receiving creatine increasing by 3.2 % ( p < 0.01 ) and the group receiving placebo decreasing by 1.0 % ( not significant ) . Changes in lean tissue mass of the arms correlated with changes in bone mineral content of the arms ( r = 0.67 ; p < 0.01 ) . Resistance training of 12 weeks increases bone mineral density in older men and creatine supplementation may provide an additional benefit for increasing regional bone mineral content . The increase in bone mineral content may be due to an enhanced muscle mass with creatine , with potentially greater tension on bone at sites of muscle attachment The rapid increase in body mass that often occurs following creatine ( Cr ) supplementation is believed to be due to intracellular water retention . The purpose of this study was to determine whether Cr consumption alters the magnetic resonance ( MR ) transverse relaxation ( T(2 ) ) distribution of skeletal muscle . Transverse relaxation can be used to model water compartments within a cell or tissue . In this double-blind study , subjects were asked to supplement their normal diet with creatine monohydrate ( 20 g day(-1 ) for 5 days ) mixed with a grape drink ( Creatine group , n = 7 ) , or the grape drink alone ( Placebo group , n = 8) . Phosphorous MR spectroscopy was used to determine the effectiveness of the supplementation protocol . Subjects that responded to the Cr supplementation ( i.e. showed a > 5 % increase in the ratio of the levels of phosphocreatine ( PCr ) and ATP ) were placed in the Creatine group . Both proton MR imaging and spectroscopy were used to acquire T(2 ) data , at 1.89 T , from the flexor digitorum profundus muscle of each subject before and after supplementation . Following the supplementation period , the Creatine group showed a gain in body mass ( 1.2 + /- 0.8 kg , P < 0.05 , mean + /- S.D. ) , and an increase in PCr/ATP ratio ( 23.8 + /- 16.4 % , P < 0.001 ) . Neither group showed any changes in intracellular pH or T(2 ) calculated from MR images . However , the spectroscopy data revealed at least three components ( > 5 ms ) at approximately 20 , 40 and 125 ms in both groups . Only in the Creatine group was there an increase in the apparent proton concentration of the two shorter components combined ( + 5.0 + /- 4.7 % , P < 0.05 ) . According to the cellular water compartment model , the changes observed in the shorter T(2 ) components are consistent with an increase in intracellular water This study aim ed to examine the efficacy of creatine supplementation , associated or not with resistance training , in vulnerable older women . A 24-week , double-blind , r and omized , placebo-controlled trial was performed . Sixty subjects were assigned to compose the following groups : placebo ( PL ) , creatine supplementation ( CR ) , placebo with resistance training ( PL+RT ) , and creatine supplementation with resistance training ( CR+RT ) . The subjects were assessed at baseline and after 24weeks . The primary outcome was muscle strength , as assessed by one-repetition maximum ( 1-RM ) tests . Secondary outcomes included appendicular lean mass , bone mass , biochemical bone markers , and physical function tests . The changes in 1-RM leg press were significantly greater in the CR+RT group ( + 19.9 % ) than in the PL ( + 2.4 % ) and the CR groups ( + 3.7 % ) , but not than in the PL+RT group ( + 15 % ) ( p=0.002 , p=0.002 , and p=0.357 , respectively ) . The CR+RT group showed superior gains in 1-RM bench press ( + 10 % ) when compared with all the other groups ( p≤0.05 ) . The CR+RT group ( + 1.31 % ) showed greater appendicular lean mass accrual than the PL ( -1.2 % ) , the CR ( + 0.3 % ) , and the PL+RT groups ( -0.2 % ) ( p≤0.05 ) . The CR and the PL+RT groups experienced comparable gains in appendicular lean mass ( p=0.62 ) , but superior to those seen in the PL group . Changes in fat mass , bone mass and serum bone markers did not significantly differ between the groups ( p>0.05 ) . In conclusion , creatine supplementation combined with resistance training improved appendicular lean mass and muscle function , but not bone mass , in older vulnerable women . Clinical trials.gov : NCT01472393 Background and Purpose : Isotonic strength training can result in neuromuscular improvements evidence d in other forms of muscular effort , ie , isokinetic or isometric , especially in young subjects ; however , it is unclear if older muscle maintains this same adaptive ability . Additionally , it is not known if the benefits of resistance training can be augmented by creatine and protein supplementation in older men . Therefore , the purpose of this study was to assess changes in isokinetic parameters at varying speeds in men aged 48 to 72 years ( mean = 57 ± 2.1 ) following 16 weeks of isotonic resistance training and creatine and /or protein supplementation . Methods : Forty‐two male subjects were r and omly assigned to 1 of 4 training groups : ( 1 ) resistance training placebo ( n = 10 ) , ( 2 ) resistance trained creatine supplemented ( n = 10 ) , ( 3 ) resistance trained protein supplemented ( n = 11 ) , and ( 4 ) resistance trained creatine and protein supplemented ( n = 11 ) . The program consisted of progressive overload resistance training ( 3 d/wk ) and supplement consumption following the workout . Results : There were significant time effects ( P ≤ .05 ) for peak torque ( PT ) , time to PT , and average power for both the knee extensors and flexors at all velocities . However , no significant group or group by time interactions were noted , indicating that the supplementation protocol s had no added benefits . Conclusions : Men aged 48 to 72 years maintained their ability to improve isokinetic muscle function following isotonic training , however , supplementation did not enhance muscle adaptability PURPOSE We hypothesized that creatine supplementation would facilitate muscle anabolism by increasing the expression of growth factors and the phosphorylation of anabolic signaling molecules ; we therefore tested the responses of mRNA for IGF-I and IGF-II and the phosphorylation state of components of anabolic signaling pathways p70(s6k ) and 4E-BP1 to a bout of high-intensity resistance exercise after 5 d of creatine supplementation . METHODS In a double-blind cross-over design , muscle biopsies were taken from the m. vastus lateralis at rest and 3 and 24 h postexercise in subjects who had taken creatine or placebo for 5 d ( 21 g x d(-1 ) ) . For the first 3 h postexercise , the subjects were fed with a drink containing maltodextrin ( 0.3 g x kg(-1 ) body weight x h(-1 ) ) and protein ( 0.08 g x kg(-1 ) body weight x h(-1 ) ) . RESULTS After creatine supplementation , resting muscle expressed more mRNA for IGF-I ( + 30 % , P < 0.05 ) and IGF-II ( + 40 % , P = 0.054 ) . Exercise caused an increase by 3 h postexercise in IGF-I ( + 24 % , P < 0.05 ) and IGF-II ( + 48 % , P < 0.05 ) and by 24 h postexercise in IGF-I ( + 29 % , P < 0.05 ) , but this effect was not potentiated by creatine supplementation . The phosphorylation states of p70(s6k ) and 4E-BP1 were not affected by creatine at rest ; phosphorylation of both increased ( 150 - 400 % , P < 0.05 ) to similar levels under placebo and creatine conditions at 3 h postexercise plus feeding . However , the phosphorylation state of 4E-BP1 was higher in the creatine versus placebo condition at 24 h postexercise . CONCLUSION The increase in lean body mass often reported after creatine supplementation could be mediated by signaling pathway(s ) involving IGF and 4E-BP1 ABSTRACT The purpose of this study was to examine the effect of creatine supplementation on the cognitive performance of elderly people . Participants were divided into two groups , which were tested on r and om number generation , forward and backward number and spatial recall , and long-term memory tasks to establish a baseline level . Group 1 ( n = 15 ) were given 5 g four times a day of placebo for 1 week , followed by the same dosage of creatine for the second week . Group 2 ( n = 17 ) were given placebo both weeks . Participants were retested at the end of each week . Results showed a significant effect of creatine supplementation on all tasks except backward number recall . It was concluded that creatine supplementation aids cognition in the elderly Dietary supplementation ( SUP ) has become a significant part of athletic training . Studies indicate that creatine ( Cr ) can enhance short- duration , high-intensity activities . This study examined the effect of 21 days of low dose Cr SUP ( approximately 7.7 g/day ) and resistance training on force output , power output , duration of mean peak power output , and total work performed until fatigue . A double-blind protocol was used , where an individual , who was not part of any other aspect of the study , r and omly assigned subjects to creatine and placebo groups . Forty-one male university athletes were r and omly assigned to either Cr ( n = 20 ) or placebo ( n = 21 ) SUP . On the first and last day of the study , subjects were required to perform concentric bench press movements until exhaustion on an isokinetic dynamometer . The dynamometer was hard-wired to a personal computer , which provided force , velocity , and duration measures . Force and power output until fatigue , were used to determine total work , force-time , and power-time relationships . ANOVA results revealed that the Cr subjects performed more total work until fatigue , experienced significantly greater improvements in peak force and peak power , and maintained elevated mean peak power for a longer period of time . These results indicate that Cr SUP can significantly improve factors associated with short- duration , high-intensity activity UNLABELLED Creatine monohydrate ( CrM ) administration may enhance high intensity exercise performance and increase body mass , yet few studies have examined for potential adverse effects , and no studies have directly considered potential gender differences . PURPOSE The purpose of this study was to examine the effect of acute creatine supplementation upon total and lean mass and to determine potential side effects in both men and women . METHODS The effect of acute CrM ( 20 g x d(-1 ) x 5 d ) administration upon systolic , diastolic , and mean BP , plasma creatinine , plasma CK activity , and body composition was examined in 15 men and 15 women in a r and omized , double-blind experiment . Additionally , ischemic isometric h and grip strength was measured before and after CrM or placebo ( PL ) . RESULTS CrM did not affect blood pressure , plasma creatinine , estimated creatinine clearance , plasma CK activity , or h and grip strength ( P > 0.05 ) . In contrast , CrM significantly increased fat-free mass ( FFM ) and total body mass ( P < 0.05 ) as compared with PL , with no changes in body fat . The observed mass changes were greater for men versus women . CONCLUSIONS These findings suggest that acute CrM administration does not affect blood pressure , renal function , or plasma CK activity , but increases FFM . The effect of CrM upon FFM may be greater in men as compared with that in women 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 . To investigate the effects of an oral creatine supplementation in older adults , 32 elderly subjects ( 67 - 80 years ; 16 females , 16 males ) were r and omly assigned to four equivalent subgroups ( control-creatine ; control-placebo ; trained-creatine ; trained-placebo ) based on whether or not they took part in an 8-week strength training programme and an 8-week oral creatine monohydrate creatine supplementation programme . The strength training programme consisted of three sets of eight repetitions at 80 % of one-repetition maximum , for leg press , leg extension and chest press , 3 days a week . The 52-day supplementation programme consisted of 20 g of creatine monohydrate ( or glucose ) and 8 g of glucose per day for the initial 5 days followed by 3 g of creatine monohydrate ( or glucose ) , and 2 g of glucose per day . Prior to and after the training and supplementation periods , body mass , body fat , lower limb muscular volume , 1- , 12-repetitions maxima and isometric intermittent endurance tests for leg press , leg extension and chest press were determined . In all groups , no significant changes in anthropometric parameters were observed . For all movements , the increases in 1- and 12-repetitions maxima were greater ( P < 0.02 ) in trained than control subjects . No significant interactions ( supplementation/training/time ) were observed for the 1- , 12-repetitions maxima , and the isometric intermittent endurance , whatever the movement considered . We conclude that oral creatine supplementation does not provide additional benefits for body composition , maximal dynamical strength , and dynamical and isometric endurances of healthy elderly subjects , whether or not it is associated with an effective strength training PURPOSE To study the effect of creatine ( Cr ) supplementation combined with resistance training on muscular performance and body composition in older men . METHODS Thirty men were r and omized to receive creatine supplementation ( CRE , N = 16 , age = 70.4 + /- 1.6 yr ) or placebo ( PLA , N = 14 , age = 71.1 + /- 1.8 yr ) , using a double blind procedure . Cr supplementation consisted of 0.3-g Cr.kg(-1 ) body weight for the first 5 d ( loading phase ) and 0.07-g Cr.kg(-1 ) body weight thereafter . Both groups participated in resistance training ( 36 sessions , 3 times per week , 3 sets of 10 repetitions , 12 exercises ) . Muscular strength was assessed by 1-repetition maximum ( 1-RM ) for leg press ( LP ) , knee extension ( KE ) , and bench press ( BP ) . Muscular endurance was assessed by the maximum number of repetitions over 3 sets ( separated by 1-min rest intervals ) at an intensity corresponding to 70 % baseline 1-RM for BP and 80 % baseline 1-RM for the KE and LP . Average power ( AP ) was assessed using a Biodex isokinetic knee extension/flexion exercise ( 3 sets of 10 repetitions at 60 degrees.s(-1 ) separated by 1-min rest ) . Lean tissue ( LTM ) and fat mass were assessed using dual energy x-ray absorptiometry . RESULTS Compared with PLA , the CRE group had significantly greater increases in LTM ( CRE , + 3.3 kg ; PLA , + 1.3 kg ) , LP 1-RM ( CRE , + 50.1 kg ; PLA + 31.3 kg ) , KE 1-RM ( CRE , + 14.9 kg ; PLA , + 10.7 kg ) , LP endurance ( CRE , + 47 reps ; PLA , + 32 reps ) , KE endurance ( CRE , + 21 reps ; PLA + 14 reps ) , and AP ( CRE , + 26.7 W ; PLA , + 18 W ) . Changes in fat mass , fat percentage , BP 1-RM , and BP endurance were similar between groups . CONCLUSION Creatine supplementation , when combined with resistance training , increases lean tissue mass and improves leg strength , endurance , and average power in men of mean age 70 yr Creatine supplementation in close proximity to resistance training may be an important strategy for increasing muscle mass and strength ; however , it is unknown whether creatine supplementation before or after resistance training is more effective for aging adults . Using a double-blind , repeated measures design , older adults ( 50 - 71 years ) were r and omized to 1 of 3 groups : creatine before ( CR-B : n = 15 ; creatine ( 0.1 g/kg ) immediately before resistance training and placebo ( 0.1 g/kg cornstarch maltodextrin ) immediately after resistance training ) , creatine after ( CR-A : n = 12 ; placebo immediately before resistance training and creatine immediately after resistance training ) , or placebo ( PLA : n = 12 ; placebo immediately before and immediately after resistance training ) for 32 weeks . Prior to and following the study , body composition ( lean tissue , fat mass ; dual-energy X-ray absorptiometry ) and muscle strength ( 1-repetition maximum leg press and chest press ) were assessed . There was an increase over time for lean tissue mass and muscle strength and a decrease in fat mass ( p < 0.05 ) . CR-A result ed in greater improvements in lean tissue mass ( Δ 3.0 ± 1.9 kg ) compared with PLA ( Δ 0.5 ± 2.1 kg ; p < 0.025 ) . Creatine supplementation , independent of the timing of ingestion , increased muscle strength more than placebo ( leg press : CR-B , Δ 36.6 ± 26.6 kg ; CR-A , Δ 40.8 ± 38.4 kg ; PLA , Δ 5.6 ± 35.1 kg ; chest press : CR-B , Δ 15.2 ± 13.0 kg ; CR-A , Δ 15.7 ± 12.5 kg ; PLA , Δ 1.9 ± 14.7 kg ; p < 0.025 ) . Compared with resistance training alone , creatine supplementation improves muscle strength , with greater gains in lean tissue mass result ing from post-exercise creatine supplementation We examined the effect of glycogen-depleting exercise on subsequent muscle total creatine ( TCr ) accumulation and glycogen re synthesis during postexercise periods when the diet was supplemented with carbohydrate ( CHO ) or creatine ( Cr ) + CHO . Fourteen subjects performed one-legged cycling exercise to exhaustion . Muscle biopsies were taken from the exhausted ( Ex ) and nonexhausted ( Nex ) limbs after exercise and after 6 h and 5 days of recovery , during which CHO ( CHO group , n = 7 ) or Cr + CHO ( Cr+CHO group , n = 7 ) supplements were ingested . Muscle TCr concentration ( [ TCr ] ) was unchanged in both groups 6 h after supplementation commenced but had increased in the Ex ( P < 0.001 ) and Nex limbs ( P < 0.05 ) of the Cr+CHO group after 5 days . Greater TCr accumulation was achieved in the Ex limbs ( P < 0.01 ) of this group . Glycogen was increased above nonexercised concentrations in the Ex limbs of both groups after 5 days , with the concentration being greater in the Cr+CHO group ( P = 0.06 ) . Thus a single bout of exercise enhanced muscle Cr accumulation , and this effect was restricted to the exercised muscle . However , exercise also diminished CHO-mediated insulin release , which may have attenuated insulin-mediated muscle Cr accumulation . Ingesting Cr with CHO also augmented glycogen supercompensation in the exercised muscle Objectives : Creatine and whey protein are supplements believed to have an ergogenic effect . Very little is known regarding the effects of these dietary supplements in older men . The purpose of this study was to determine the effect of creatine and whey protein supplements , consumed independently and in combination , on total and regional body composition in middle-aged men during a resistance-training program . Design , Setting , Participants : Forty-two men were r and omly assigned to four groups to receive supplements according to a double-blind protocol . Groups consumed their supplements three times per week immediately following their resistance training sessions . The groups were : 1 ) placebo ( 480 ml of Gatorade ® ) ; 2 ) creatine ( 480 ml of Gatorade ® plus 5 grams of creatine ) ; 3 ) whey protein ( 480 ml of Gatorade ® plus 35 grams of whey protein powder ) ; and 4 ) whey protein/creatine ( 480 ml of Gatorade ® plus 5 grams of creatine and 35 grams of whey protein powder ) . All groups participated in resistance training 3 times per week for 14 weeks . Measurements : At the beginning and end of the study , total and regional measures of body composition ( DXA ) and total ( TBW ) , intracellular ( ICW ) , and extracellular ( ECW ) body water ( Multifrequency BIA ) were measured and 3-day diet records were completed . Results : There were significant training effects for regional arm fat ( decrease ) , regional arm bone free-fat free mass ( BF-FFM-increase ) , total body BF-FFM ( increase ) , ICW ( increase ) , and ECW ( increase ) but no significant group effects and only one significant group by training interaction ( ECW ) . There were no significant changes for total calorie , carbohydrate , fat or protein intake for any of the groups from pre study to post- study testing . Conclusion : The results from this study suggest that supplementation with creatine , whey protein , or a combination of creatine and whey protein , when combined with resistance training in middle-aged men , have no added benefit to changes that occur to body composition due to resistance training alone We sought to determine whether creatine monohydrate ( CrM ) supplementation would enhance the increases in strength and fat-free mass that develop during resistance exercise training in older adults . Twenty-eight healthy men and women over the age of 65 years participated in a whole-body resistance exercise program 3 days per week for 14 weeks . The study participants were r and omly allocated , in a double-blind fashion , to receive either CrM ( 5 g/d + 2 g of dextrose ; n = 14 ) or placebo ( 7 g of dextrose ; n = 14 ) . The primary outcome measurements included the following : total body mass , fat-free mass , one-repetition maximum strength for each body part , isometric knee extension , h and grip , and dorsiflexion strength , chair st and performance , 30-m walk test , 14-stair climb performance , muscle fiber type and area , and intramuscular total creatine . Fourteen weeks of resistance exercise training result ed in significant increases in all measurements of strength and functional tasks and muscle fiber area for both groups ( p < .05 ) . CrM supplementation result ed in significantly greater increases in fat-free mass and total body mass , as compared with placebo ( p < .05 ) . The CrM group also showed a greater increase in isometric knee extension strength in men and women , as compared with placebo ( p < .05 ) , and also greater gains in isometric dorsiflexion strength ( p < .05 ) , but in men only . There was a significant increase in intramuscular total creatine in the CrM group ( p < .05 ) . Finally , there were no significant side effects of treatment or exercise training . This study confirms that supervised heavy resistance exercise training can safely increase muscle strength and functional capacity in older adults . The addition of CrM supplementation to the exercise stimulus enhanced the increase in total and fat-free mass , and gains in several indices of isometric muscle strength |
11,263 | 31,678,956 | There were limited data to identify the optimal form of behavioural SCI for the target population .
Intense multimodal behavioural counselling that uses incentives and peer facilitators , delivered in a community setting and tailored to individual needs indicated a positive impact on smoking outcomes .
CONCLUSION Tailored , multimodal behavioural interventions embedded in local communities could potentially support cessation among older , deprived smokers . | INTRODUCTION The associations between smoking prevalence , socioeconomic group and lung cancer outcomes are well established .
There is currently limited evidence for how inequalities could be addressed through specific smoking cessation interventions ( SCIs ) for a lung cancer screening eligible population .
This systematic review aims to identify the behavioural elements of SCIs used in older adults from low socioeconomic groups , and to examine their impact on smoking abstinence and psychosocial variables . | Background Smoking cessation was examined among high-risk participants in the UK Lung Cancer Screening ( UKLS ) Pilot Trial of low-dose CT screening . Methods High-risk individuals aged 50–75 years who completed baseline question naires were r and omised to CT screening ( intervention ) or usual care ( no screening control ) . Smoking habit was determined at baseline using self-report . Smokers were asked whether they had quit smoking since joining UKLS at T1 ( 2 weeks after baseline scan results or control assignment ) and T2 ( up to 2 years after recruitment ) . Intention-to-treat ( ITT ) regression analyses were undertaken , adjusting for baseline lung cancer distress , trial site and sociodemographic variables . Results Of a total 4055 individuals r and omised to CT screening or control , 1546 were baseline smokers ( 759 intervention , 787 control ) . Smoking cessation rates were 8 % ( control n=36/479 ) versus 14 % ( intervention n=75/527 ) at T1 and 21 % ( control n=79/377 ) versus 24 % ( intervention n=115/488 ) at T2 . ITT analyses indicated that the odds of quitting among screened participants were significantly higher at T1 ( adjusted OR ( aOR ) 2.38 , 95 % CI 1.56 to 3.64 , p<0.001 ) and T2 ( aOR 1.60 , 95 % CI 1.17 to 2.18 , p=0.003 ) compared with control . Intervention participants who needed additional clinical investigation were more likely to quit in the longer term compared with the control group ( aOR 2.29 , 95 % CI 1.62 to 3.22 , p=0.007 ) and those receiving a negative result ( aOR 2.43 , 95 % CI 1.54 to 3.84 , p<0.001 ) . Conclusions CT lung cancer screening for high-risk participants presents a teachable moment for smoking cessation , especially among those who receive a positive scan result . Further behavioural research is needed to evaluate optimal strategies for integrating smoking cessation intervention with stratified lung cancer screening . Trial registration number Results , IS RCT N Background : The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large r and omised controlled trials . Methods : This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial ( DLCST ) , a 5-year r and omised controlled trial comprising 4104 subjects ; 2052 subjects received annual low-dose CT scan ( CT group ) and 2052 received no intervention ( control group ) . Participants were healthy current and former smokers ( > 4 weeks since smoking cessation ) with a tobacco consumption of > 20 pack years . Smoking habits were determined at baseline and at annual screening . Smoking status was verified using exhaled carbon monoxide levels . Lung function tests , nicotine dependency and motivation to quit smoking were assessed . Quit rates and relapse rates were determined at 1-year follow-up for all subjects . Results : At 1 year the quit rates among smokers were 11.9 % in the CT group and 11.8 % in the control group ( p = 0.95 ) . Relapse rates for former smokers were 10.0 % and 10.5 % in the CT and control groups , respectively ( p = 0.81 ) . Significant predictors ( p<0.05 ) for smoking cessation were : high motivation to quit , low dependency , low ratio of forced expiratory volume in 1 s to forced vital capacity , low pack years , higher age , longer period of abstinence and CT findings necessitating 3-month repeat CT scans . Conclusions : Overall , quit rates were similar in the CT and control group at 1-year follow-up , with a net quit rate of 6.0 % . Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later Background Lung cancer screening may provide a new opportunity for attempts to quit among smokers or might delay smoking cessation , but studies to date failed to provide evidence for this . This study investigated the effect of lung cancer screening on smoking abstinence in male smokers participating in the Dutch – Belgian r and omised controlled lung cancer screening trial ( NELSON trial ) . Methods In the NELSON trial , 50- to 75-year-old participants at high risk for developing lung cancer were r and omised to either lung cancer screening or no screening . Smoking behaviour was evaluated in two r and om sample s of male smokers in the screen ( n=641 ) and control arm ( n=643 ) before ( T0 ) and 2 years after r and omisation ( T1 ) . In addition , the data were also analysed by intention-to-treat ( ITT ) analysis , as recommended in smoking cessation intervention trials , although non-response in screening trials can also be due to reasons other than continued smoking . Results Almost 17 % ( 16.6 % ) of the trial participants quit smoking , which is higher than the 3–7 % found in the general adult population . However , screening was associated with a lower prolonged abstinence rate ( 14.5 % ) compared with no screening ( 19.1 % ) ( OR 1.40 , 95 % CI 1.01 to 1.92 ; p<0.05 ) . No stastistically significant difference was found after performing an ITT analysis . Conclusions This study showed that all trial participants were inclined to stop smoking more than average , which suggests that screening is a teachable moment to improve smoking behaviour . In those who underwent screening the smoking abstinence rate was significantly lower than for the control group , although the difference was modest . After ITT analysis this difference was no longer observed . Clinical trial number IS RCT N63545820 Abstract Introduction In the German lung cancer screening trial LUSI , smoking cessation counseling ( SCC ) was offered to all participants at time of r and omization , and smoking habits were asked for within annual question naire inquiries . We analyzed the smoking habits of the participants within the first 2 years of follow-up and especially the potential effect of the SCC on these habits . Material s and methods We used the smoking data of the initial inquiry on which the decision on invitation to the study was based , the socio-economic data of the question naire filled-in at time of r and omization , the psycho-social data obtained during the SCC , and the annual question naire data of the first two annual follow-up screening rounds . Results Smoking prevalence decreased in the entire cohort significantly by 4 % , whereby the decrease was with 4.5 % statistically not significantly higher in the control arm than in the screening arm with 3.4 % . The decline was much stronger in the subgroup of attendees to stop-smoking counseling and mounted up therein to 10 % . In some participants , an increase of readiness to quit smoking was observed during the counseling hour , but did not show effects on smoking status 2 years later . Discussion We did not see a tendency to increased smoking among participants of the intervention arm or the entire study . The decline of smoking prevalence among the attendees of the counseling might be due to self- selection . Since the issue of effectiveness of smoking cessation counseling is important , further research with r and omization into offering counseling or no intervention should be taken into consideration Objectives To evaluate the real-life effect of an evidence -based Gold St and ard Programme ( GSP ) for smoking cessation interventions in disadvantaged patients and to identify modifiable factors that consistently produce the highest abstinence rates . Design Observational prospect i ve cohort study . Setting GSPs in pharmacies , hospitals and communities in Denmark , reporting to the national Smoking Cessation Data base . Participants Disadvantaged patients , defined as patients with a lower level of education and those receiving unemployment benefits . Interventions 6-week manualised GSP smoking cessation interventions performed by certified staff . Main outcome measures 6 months of continuous abstinence , response rate : 80 % . Results Continuous abstinence of the 16 377 responders was 34 % ( of all 20 588 smokers : 27 % ) . Continuous abstinence was lower in 5738 smokers with a lower educational level ( 30 % of responders and 23 % of all ) and in 840 unemployed ( 27 % of responders and 19 % of all ) . In respect to modifiable factors , continuous abstinence was found more often after programmes in one-on-one formats ( vs group formats ) among patients with a lower educational level , 34 % ( vs 25 % , p=0.037 ) , or among unemployed , 35 % ( vs 24 % , p=0.099 ) . The variable ‘ format ’ stayed in the final model of multivariable analyses in patients with a lower educational level , OR=1.31 ( 95 % CI 1.05 to 1.63 ) . Conclusions Although continuous abstinence was lower among disadvantaged smokers , the absolute difference was small . If the programme had been as effective in disadvantaged as in non-disadvantaged groups , there would have been an extra 46 or 8 quitters annually , respectively . Promoting individual interventions among those with a low education may increase the effectiveness of GSP Deux etudes longitudinales , prospect ives , examinent le role du soutien social dans le maintien de la decision de ne plus fumer : soutien d'un partenaire ; existence d'un climat social encourageant le sevrage ; participation a un reseau social . Part de chacun des facteurs dans le maintien de la decision et l'absence de rechute . Etudes Importance While the proportion of adults who smoke cigarettes has declined substantially in the past decade , socioeconomic disparities in cigarette smoking remain . Few interventions have targeted low socioeconomic status ( SES ) and minority smokers in primary care setting s. Objective To evaluate a multicomponent intervention to promote smoking cessation among low-SES and minority smokers . Design , Setting , and Participants For this prospect i ve , unblinded , r and omized clinical trial conducted between May 1 , 2015 , and September 4 , 2017 , adults 18 years and older who spoke English , smoked 10 or more cigarettes per day in the past week , were contemplating or preparing to quit smoking , and had a primary care clinician were recruited from general internal medicine and family medicine practice s at 1 large safety-net hospital in Boston , Massachusetts . Interventions Patients were r and omized to a control group that received an enhancement of usual care ( n = 175 participants ) or to an intervention group that received up to 4 hours of patient navigation delivered over 6 months in addition to usual care , as well as financial incentives for biochemically confirmed smoking cessation at 6 and 12 months following enrollment ( n = 177 participants ) . Main Outcomes and Measures The primary outcome determined a priori was biochemically confirmed smoking cessation at 12 months . Results Among 352 patients who were r and omized ( mean [ SD ] age , 50.0 [ 11.0 ] years ; 191 women [ 54.3 % ] ; 197 participants who identified as non – Hispanic black [ 56.0 % ] ; 40 participants who identified as Hispanic of any race [ 11.4 % ] ) , all were included in the intention-to-treat analysis . At 12 months following enrollment , 21 participants [ 11.9 % ] in the navigation and incentives group , compared with 4 participants [ 2.3 % ] in the control group , had quit smoking ( odds ratio , 5.8 ; 95 % CI , 1.9 - 17.1 ; number needed to treat , 10.4 ; P < .001 ) . In prespecified subgroup analyses , the intervention was particularly beneficial for older participants ( 19 [ 19.8 % ] vs 1 [ 1.0 % ] ; P < .001 ) , women ( 17 [ 16.8 % ] vs 2 [ 2.2 % ] ; P < .001 ) , participants with household yearly income of $ 20 000 or less ( 15 [ 15.5 % ] vs 3 [ 3.1 % ] ; P = .003 ) , and nonwhite participants ( 21 [ 15.2 % ] vs 4 [ 3.0 % ] ; P < .001 ) . Conclusions and Relevance In this study of adult daily smokers at 1 large urban safety-net hospital , patient navigation and financial incentives for smoking cessation significantly increased the rates of smoking cessation . Trial Registration clinical trials.gov Identifier : |
11,264 | 18,843,742 | There was little information to draw conclusions on the overall effectiveness of interventions to relieve heartburn in pregnancy | BACKGROUND Heartburn is a common symptom in pregnancy affecting up to 80 % of women in the third trimester .
The reasons for the increase in symptoms in pregnancy are not well understood , but the effects of pregnancy hormones on the lower oesophageal sphincter and gastric clearance are thought to play a part .
A range of interventions have been used to relieve symptoms including advice on diet and lifestyle , antacids , antihistamines , and proton pump inhibitors .
The safety and effectiveness of these interventions to relieve heartburn in pregnancy have not been established .
OBJECTIVES To assess the effect of interventions to relieve heartburn in pregnancy . | BACKGROUND Published data on pregnancy outcome after exposure to H2-blockers is scarce . The aim of the present study was to evaluate the data collected by the memberships of the European Network of Teratology Information Services ( ENTIS ) . METHODS The patients were pregnant women who or whose doctor or midwife did contact a Teratology Information Service for risk assessment after the use of a H2-blocker in pregnancy . The data were prospect ively collected , i.e. before the outcome of pregnancy was known . St and ardized procedures for data collection were used by each centre . The data of the exposed women were compared to those of a control group exposed to non-teratogenic substances . RESULTS Data on the outcome of 553 pregnancies with exposure to an H2-blocker were evaluated ( ranitidine n=335 ; cimetidine n=113 , famotidine n=75 ; nizatidine n=15 , roxatidine n=15 ) . Most of them had been exposed at least in the first trimester . The incidence of premature deliveries was higher in the exposed group compared to the control group . There was no increase in the incidence of major malformations . Two pregnancies with maternal use of famotidine in early pregnancy were terminated after the prenatal diagnosis of a neural tube defect . CONCLUSION There is no indication for an increased risk of major malformations after the use of H2-blockers during pregnancy A r and omized controlled trial was performed to study the efficacy of Syn-Ergel with an active placebo in the treatment of heartburn of pregnancy in ninety-two patients completing 7 days of therapy . Syn-Ergel was significantly better ( p 0.001 ) in all groups of pre-treatment pain severity in relieving the symptoms , and had a longer duration of action , than the active placebo . Complete relief of pain was achieved in 79.5 % of Syn-Ergel treatments with a further 10 % of treatments result ing in marked easing of discomfort at 1 hour following administration . The corresponding figures for the ‘ active placebo ’ were 56 % and 20 % . The combination of an antacid and a protective mucosal coating agent would appear to be a useful approach in the treatment of heartburn of pregnancy Objective To determine whether ranitidine ( Zantac ) taken once or twice daily is effective for relieving symptoms of gastroesophageal reflux among pregnant women who had failed conservative measures . Methods Volunteers with heartburn despite antacids were sought among our obstetric clinic population for this double-blind , placebo-controlled , triple crossover trial . After a baseline week , 20 patients were r and omized to receive the three following weekly regimens : ranitidine 150 mg twice daily , placebo in the morning and ranitidine 150 mg in the evening , or placebo twice daily . Daily scores on symptom diaries , global assessment s , and number of antacids taken were compared among the 18 patients completing the study . Results The twice-daily dosage of ranitidine was the only regimen found to reduce heartburn symptoms when compared with the baseline ( P < .001 ) or a placebo ( P < .01 ) . Compared with ranitidine taken once daily , the twice-daily dosing prompted less need for antacid tablets compared with the placebo ( P < .05 versus P > .05 ) and to the baseline ( P < .001 versus P < .05 ) . The average reduction of heartburn severity using twice-daily ranitidine was 55.6 % when compared with baseline ( 95 % confidence interval [ CI ] 34.8 % , 76.5 % ) and was 44.2 % when compared with placebo ( 95 % CI 15.4 % , 72.9 % ) . Conclusion This study indicates the efficacy of ranitidine 150 mg taken twice daily , rather than once daily , for relief of gastroesophageal reflux symptoms during pregnancy A double blind comparative study comparing Mucaine , Mucaine without oxethazaine , and placebo was carried out with 50 patients with symptoms of heartburn during late pregnancy . We found that the 2 active treatments were more effective than placebo for the relief of heartburn , but there was no statistically significant difference between groups for the relief of nausea and regurgitation . There was a significant difference in the percentage of days of use of each medication , with the placebo being used least frequently . Although not statistically significant , for the 3 measures for which placebo differed from the active treatments , patients showed a better response to mucaine . This suggests that the addition of oxethazaine may be of benefit . The lack of statistical significance may be due to the relatively small number of cases , and the findings are promising . No side effects were recorded for any treatment A r and omised crossover trial was performed in 55 pregnant women who complained of heartburn to see whether alkali or acid treatment alleviated it . Each woman was given a week 's treatment with an acid mixture , an alkali mixture , and a placebo in r and omised order . Both acid and alkali mixtures were better than placebo , but there was no significant difference between the acid and alkali treatments . Together with the inconsistent reports of some patients , these findings suggest that both acid reflux and bile regurgitation may cause heartburn in pregnant women and that other factors may also play a part . Because the cause of heartburn may be difficult to determine , treatment should be empirical . If the patient does not respond to seven days ' acid treatment an alkali mixture should be prescribed ; there is a 98 % chance that one of these treatments will relieve symptoms OBJECTIVES This study is aim ed at determining the prevalence of gastrointestinal symptoms among healthy pregnant women attending antenatal clinic at the University of Maiduguri Teaching Hospital . METHODS Question naires were r and omly administered to consecutive antenatal clinic attendees until the sample size was reached . RESULTS Three hundred and seventy pregnant women were interviewed . Heart burns , easy fullness and nausea were the commonest gastrointestinal symptoms in 45 % , 40.2 % and 39.9 % of cases respectively . Primigravidae had significantly more symptoms than multiparae . There were also significantly more gastrointestinal symptoms in the first trimester of pregnancy . CONCLUSION Gastrointestinal symptoms are common among healthy pregnant women . And even though these represent well-known physiological changes , they must be carefully assessed to exclude any pathological disorder that may require intervention In a double-blind study the gastro-oesophageal sphincter pressure profile was measured in a group of twenty women in the last trimester of pregnancy , all of whom suffered from heartburn . The mean gastric and the maximum sphincter pressures were calculated from the pressure profile , and the difference between these two was defined as the barrier pressure . After resting sphincter measurement ten of the women were given 10 mg metocolopramide intravenously , and the other ten had a placebo intravenous injection ; 15 min later the sphincter pressures were measured again . Metoclopramide significantly increased the mean maximum sphincter and barrier pressures compared to the baseline pressure , and there was no significant difference between the pre- and post-injection pressures in the placebo group . However , the raised mean maximum sphincter and barrier pressures following metoclopramide were made up of four patients having very high pressures and six patients on whom metoclopramine appeared to have little effect . The clinical usefulness of metoclopramide in women in labour is discussed Background : Proton pump inhibitors are used to treat gastro‐oesophageal reflux and peptic ulcers . Gastro‐oesophageal reflux is a common condition in pregnancy . Human pregnancy experience with lansoprazole or pantoprazole is very limited . More data exist on the safety of omeprazole in pregnancy OBJECTIVES To evaluate the magnitude of possible fetal risks involved in maternal use of omeprazole during pregnancy . STUDY DESIGN Infants whose mothers used omeprazole during pregnancy were identified from the Swedish Medical Birth Registry . A total of 955 exposed infants born in 1995 - 1999 were identified : 863 of which were exposed in early pregnancy and 131 later in pregnancy and 39 who had been exposed both in early and late pregnancy . Delivery outcome was studied : presence of congenital malformations , perinatal survival , low birth weight , low Apgar score and hospitalization up to the end of 1997 . RESULTS No clear-cut indication of ill effects were seen . Five infants were stillborn and the rate of congenital heart defects was slightly increased , but both effects may be r and om . CONCLUSIONS The present data set and previously published data give no reason for concern after exposure for omeprazole during pregnancy |
11,265 | 31,953,656 | mrTRG 1 showed high specificity for pCR and ≤ypT1 , but suboptimal sensitivity .
mrTRG 1 or 2 showed higher sensitivity for pCR and ≤ypT1 , but lower specificity .
Because of the suboptimal sensitivity of mrTRG 1 , it might be limited as a criterion for less aggressive treatment after neoadjuvant chemoradiotherapy . •
Magnetic resonance tumor regression grade 1 shows high specificity for pCR and ≤ypT1 , but suboptimal sensitivity . •
Magnetic resonance tumor regression grade 1 or 2 shows higher sensitivity for pCR and ≤ypT1 , but lower specificity than magnetic resonance tumor regression grade 1 alone | To determine the diagnostic accuracy of magnetic resonance tumor regression grade ( mrTRG ) for pathological complete response ( pCR ) and its correlation with pathological findings . | Purpose A pathologic complete response ( pCR ; ypT0N0 ) of a rectal tumor after neoadjuvant radiochemotherapy ( RCT ) is associated with an excellent prognosis . Several retrospective studies have investigated the effect of increasing the delay after RCT . The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate . Methods GRECCAR6 was a phase III , multicenter , r and omized , open-label , parallel-group controlled trial . Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT ( 45 to 50 Gy with fluorouracil or capecitabine ) were included . Patients were r and omly included in the 7-week or the 11-week ( 11w ) group . Primary end point was the pCR rate defined as a ypT0N0 specimen ( NCT01648894 ) . Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015 . The majority of the tumors were cT3 ( 82 % ) . After RCT , surgery was not performed in nine patients ( 3.4 % ) because of the occurrence of distant metastasis ( n = 5 ) or other reasons . Two patients underwent local resection of the tumor scar . A total of 47 ( 18.6 % ) specimens were classified as ypT0 ( four had invaded lymph nodes [ 8.5 % ] ) . The primary end point ( ypT0N0 ) was not different ( 7 weeks : 20 of 133 , 15.0 % v 11w : 23 of 132 , 17.4 % ; P = .5983 ) . Morbidity was significantly increased in the 11w group ( 44.5 % v 32 % ; P = .0404 ) as a result of increased medical complications ( 32.8 % v 19.2 % ; P = .0137 ) . The 11w group had a worse quality of mesorectal resection ( complete mesorectum [ I ] 78.7 % v 90 % ; P = .0156 ) . Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection . A longer waiting period may be associated with higher morbidity and more difficult surgical resection BACKGROUND Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy , to potentially avoid morbidity and side-effects of rectal excision . The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer . METHODS We did a prospect i ve , r and omised , open-label , multicentre , phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer . Patients aged 18 years and older with stage T2T3 lower rectal carcinoma , of maximum size 4 cm , who had a good clinical response to neoadjuvant chemoradiotherapy ( residual tumour ≤2 cm ) were central ly r and omly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery . R and omisation , which was done via the internet , was not stratified and used permuted blocks of size eight . In the local excision group , a completion total mesorectal excision was required if tumour stage was ypT2 - 3 . The primary endpoint was a composite outcome of death , recurrence , morbidity , and side-effects at 2 years after surgery , to show superiority of local excision over total mesorectal excision in the modified intention-to-treat ( ITT ) population ( expected proportions of patients having at least one event were 25 % vs 60 % for superiority ) . This trial was registered with Clinical Trials.gov , number NCT00427375 . FINDINGS From March 1 , 2007 , to Sept 24 , 2012 , 186 patients received chemoradiotherapy and were enrolled in the study . 148 good clinical responders were r and omly assigned to treatment , three were excluded ( because they had metastatic disease , tumour > 8 cm from anal verge , and withdrew consent ) , and 145 were analysed : 74 in the local excision group and 71 in the total mesorectal excision group . In the local excision group , 26 patients had a completion total mesorectal excision . At 2 years in the modified ITT population , one or more events from the composite primary outcome occurred in 41 ( 56 % ) of 73 patients in the local excision group and 33 ( 48 % ) of 69 in the total mesorectal excision group ( odds ratio 1·33 , 95 % CI 0·62 - 2·86 ; p=0·43 ) . In the modified ITT analysis , there was no difference between the groups in all components of the composite outcome , and superiority was not shown for local excision over total mesorectal excision . INTERPRETATION We failed to show superiority of local excision over total mesorectal excision , because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects , and compromised the potential advantages of local excision . Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy . FUNDING National Cancer Institute of France , Sanofi , Roche Pharma Purpose To study the predictive and prognostic value of magnetic resonance imaging (MRI)–assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer . Methods This study included 79 patients who had T3 or T4 and /or N+ rectal cancer treated with long-course neoadjuvant chemoradiation . MRI-assessed tumor regression grade ( mrTRG ) was assessed in 64 patients . MRIs were review ed by the study radiologist . Surgical and pathologic reports for those who underwent surgery were review ed . Disease-free survival ( DFS ) was estimated . Progression during therapy , local relapse , metastasis , and death result ing from the tumor were classified as events . Statistical significance was calculated . Results In 11 patients , the tumor completely disappeared on MRI ; that is , it had an mrTRG of 1 . All but one patient , who chose deferred surgery , had a complete pathologic response ( pCR ) , with a positive predictive value of nearly 100 % . Of the 20 patients who had an mrTRG of 2 on MRI , six had a pCR . mrTRG 3 , mrTRG 4 , and mrTRG 5 were detected in 24 , six , and three patients , respectively , of whom only one patient had a pCR . The 2-year DFS was 77 % . The mrTRG was significant for DFS . The 2-year DFS was 88 % for patients with a good response versus 66 % for those with a poor response ( P = .046 ) . Conclusion MRI-assessed complete tumor response was strongly correlated with pCR and , therefore , can be used as a surrogate marker to predict absence of viable tumor cells . Our results can be used to implement use of mrTRGs in larger prospect i ve correlative studies as a tool to select patients for whom deferred surgery may be appropriate . Also , those with a poor response may be offered further treatment options before definitive surgery OBJECTIVE The purpose of this study was to evaluate the prognostic relevance of a modified 3-point MRI-based tumor regression grading system incorporating DWI for patients with locally advanced rectal cancer after preoperative chemoradiotherapy ( CRT ) . MATERIAL S AND METHODS Between March 2012 and September 2013 , 118 consecutively registered patients with middle or lower locally advanced rectal cancer who underwent CRT followed by surgery were enrolled in this retrospective study . Two radiologists in consensus assessed MRI tumor regression grade ( mrTRG ) based on T2-weighted images and high b value DW images ( 0 and 1000 s/mm2 ) using the following grade s : 0 , complete regression ( no obvious tumor ) ; 1 , intermediate regression ( dominant fibrosis , regression > 50 % ) ; 2 , poor regression ( dominant tumor , regression ≤ 50 % ) . Multivariate analysis with a Cox regression model was performed to evaluate the association between modified mrTRG and 3-year disease-free survival ( DFS ) rate . A Kaplan-Meier method with a log-rank test was used to compare the DFS rate between responder ( grade s 0 and 1 ) and nonresponder ( grade 2 ) groups . RESULTS Both the accuracy ( 72.9 % vs 38.1 % ; p < 0.001 ) and the interreader agreement ( κ = 0.580 vs 0.338 ; p < 0.001 ) of modified 3-point mrTRG were improved over the established 5-point mrTRG . Modified mrTRG ( adjusted hazard ratio , 2.505 ; 95 % CI , 1.231 - 5.100 ) was independently associated with 3-year DFS rate ( p = 0.011 ) . There was also a significant difference in the 3-year DFS rate between responders ( 73.8 % ; 95 % CI , 64.2 - 81.3 % ) and nonresponders ( 41.7 % ; 95 % CI , 10.9 - 70.8 % ) ( p = 0.028 ) . CONCLUSION In patients with middle or lower locally advanced rectal cancer , the modified 3-point mrTRG incorporating DWI was independently associated with the 3-year DFS rate after CRT followed by surgery . The grading scale may be used as a surrogate for expected prognosis of preoperative CRT . Further prospect i ve trials are warranted Introduction : Nonoperative management ( NOM ) of rectal cancer after a complete clinical response ( cCR ) to neoadjuvant therapy is controversial . In this article , we retrospectively review ed the outcomes of patients managed with selective NOM after a cCR to neoadjuvant treatment and compared these with patients who underwent st and ard rectal resection with a pathological complete response ( pCR ) . Methods : Patients completing neoadjuvant chemoradiotherapy ( CRT ) for stage I to III rectal cancer between January 2006 and August 2010 were retrospectively review ed . Median follow-up was calculated in months after completion of CRT . Results : Thirty-two patients ( median follow-up 28 months ) were treated by NOM after a cCR . Among 265 treated by CRT and rectal resection , 57 patients ( 22 % ) had a pCR and formed the control group ( median follow-up 43 months ) . Factors associated with selective use of NOM included lower pretreatment stage , older age , and distal tumor location ( P < 0.05 ) . In the NOM group , 6 recurred locally ( median 11 months , range 7–14 ) , 3 of whom also had concurrent distant recurrence . All 6 local failures were controlled by salvage rectal resection with no further local recurrence of disease ( median follow-up 17 months ) . In the rectal resection/pCR group , there were no local failures . The 2-year distant disease-free survival ( 88 % vs 98 % , P = 0.27 ) and overall survival ( 96 % vs 100 % , P = 0.56 ) were similar for NOM and rectal resection/pCR groups . Conclusions : Rectal resection was successfully avoided in 81 % of patients selected for NOM . When combined with salvage surgery , NOM appears to achieve similar local and distant disease control compared with patients with a pCR treated by rectal resection . Longer follow-up and prospect i ve trials are warranted to evaluate this promising treatment option PURPOSE To retrospectively assess accuracy of magnetic resonance ( MR ) imaging after radiation therapy with concomitant chemotherapy for downsizing of the primary lesion to ypT0 - 2 tumor confined to rectal wall in locally advanced rectal cancer , with histopathologic findings as reference st and ard , and to evaluate additional value of volumetric analysis . MATERIAL S AND METHODS The institutional review board approved the study and waived informed consent . Sixty-seven patients met criteria of the study . T2-weighted MR images obtained before and after radiation therapy with concomitant chemotherapy were assessed for tumor stage by expert abdominal radiologist , colorectal surgeon , and general radiologist . Sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) were calculated ; tumor volume was measured ( compared with Mann-Whitney U test ) . Findings were correlated with histopathologic findings . RESULTS Sixty-seven patients ( 38 men , 29 women ; mean age , 63 years ) who underwent radiation therapy with concomitant chemotherapy and surgery ( all but one ) were evaluated . The PPV for prediction of tumor confined to rectal wall ( ypT0 - 2 ) was 91 % ( 10 of 11 ) , 86 % ( six of seven ) , and 88 % ( seven of eight ) for expert abdominal radiologist , surgeon , and general radiologist , respectively . In 24 patients , sensitivity was 42 % ( 10 ) , 25 % ( six ) , and 29 % ( seven ) . ypT0 - 2 tumors had significantly smaller volumes than did ypT3 - 4 tumors before radiation therapy with concomitant chemotherapy ( 55 vs 92 cm(3 ) , P = .038 ) . Volume reduction rates were significantly higher in ypT0 - 2 than in ypT3 - 4 tumors ( 89 % vs 61 % , P < .001 ) . If volume before radiation therapy with concomitant chemotherapy was 50 cm(3 ) or smaller and volume reduction rate was 75 % or higher , excised tumor was always confined to rectal wall ( ypT0 - 2 ) . By using these criteria , 43 % ( six of 14 ) of cases with overstaging could have been predicted to be ypT0 - 2 tumors correctly . CONCLUSION Downsizing to ypT0 - 2 tumors can be accurately predicted by combining morphologic tumor staging predictions with results from volumetric analyses . MR images obtained after radiation therapy with concomitant chemotherapy might be helpful in more individualized treatment planning Objective : This study aim ed to vali date a magnetic resonance imaging ( MRI ) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane ( mrLRP ) . Background : Low rectal cancer oncological outcomes remain a global challenge , evidence d by high pathological circumferential resection margin ( pCRM ) rates and unacceptable variations in permanent colostomies . Methods : Between 2008 and 2012 , a prospect i ve , observational , multicenter study ( MERCURY II ) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge . MRI assessed the following : mrLRP “ safe or unsafe , ” venous invasion ( mrEMVI ) , depth of spread , node status , tumor height , and tumor quadrant . MRI-based treatment recommendations were compared against final management and pCRM outcomes . Results : Overall pCRM involvement was 9.0 % [ 95 % confidence interval ( CI ) , 5.9–12.3 ] , significantly lower than previously reported rates of 30 % . Patients with no adverse MRI features and a “ safe ” mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy , result ing in a 1.6 % pCRM rate . The pCRM rate increased 5-fold for an “ unsafe ” compared with “ safe ” preoperative mrLRP [ odds ratio ( OR ) = 5.5 ; 95 % CI , 2.3–13.3 ) ] . Posttreatment MRI re assessment indicated a “ safe ” ymrLRP in 33 of 113 ( 29.2 % ) , none of whom had ypCRM involvement . In contrast , persistent “ unsafe ” ymrLRP posttherapy result ed in 17.5 % ypCRM involvement . Further independent MRI assessed risk factors were EMVI ( OR = 3.8 ; 95 % CI , 1.5–9.6 ) , tumors less than 4.0 cm from the anal verge ( OR = 3.4 ; 95 % CI , 1.3–8.8 ) , and anterior tumors ( OR = 2.8 ; 95 % CI , 1.1–6.8 ) . Conclusions : The study vali date d MRI low rectal plane assessment , reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy . It also highlights the importance of posttreatment restaging PURPOSE To prospect ively differentiate , at magnetic resonance ( MR ) imaging , patients with locally advanced nonmucinous rectal cancer who will respond to long-course chemotherapy and radiation therapy ( CRT ) from those who will not respond , with histopathologic results as the reference st and ard . MATERIAL S AND METHODS Institutional review board approval for this study was obtained , and all patients provided written informed consent . High-spatial-resolution T2-weighted MR images were acquired before and 6 - 8 weeks after CRT in 53 patients ( 33 men , 20 women ; mean age , 63 years ; age range , 42 - 79 years ) . Patients were categorized as responders to CRT ( patients with T3 cancer that converted to T2 or a lower stage , patients with T4 cancer that converted to T3 or a lower stage ) or as nonresponders ( patients with stable or progressive disease ) . At the posttreatment MR imaging examination , a decrease in signal intensity was considered to represent a morphologic response with fibrosis . Before CRT and surgery , tumor volume was calculated at MR imaging by multiplying cross-sectional area by section thickness . Tumor length was measured at MR imaging and in the histopathologic specimen . Nodal downstaging was evaluated . The relationship between pathologic response , morphologic MR imaging response , and percentage volume reduction was evaluated with the Mann-Whitney-Wilcoxon two- sample test . RESULTS Morphologic response assessment with MR imaging achieved a positive predictive value ( PPV ) of 84.2 % ( 32 of 38 ) and a negative predictive value ( NPV ) of 66.7 % ( 10 of 15 ) . Volume reduction extent ( > or = 70 % ) was significantly different between patients in whom disease was downstaged and those in whom it was not downstaged ( P = .000005 ) and showed additional diagnostic value , with an overall accuracy of 86.8 % ( 46 of 53 ) . Presurgical MR imaging and histopathologic tumor length did not show a significant difference . MR imaging accuracy for lymph node ( N ) stage was 86.8 % ( 46 of 53 ) on the basis of morphologic criteria . CONCLUSION After CRT , morphologic and volumetric evaluation at MR imaging had a high PPV and a low NPV for response assessment . The detection of small clusters of residual tumor cells within fibrosis remains a problem . SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/250/3/730/DC1 PURPOSE To assess magnetic resonance imaging ( MRI ) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospect ively enrolled , multicenter study . METHODS In a prospect i ve cohort study , 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T , N and circumferential resection margin ( CRM ) status . Tumor regression grade ( TRG ) was also assessed by MRI . Overall survival ( OS ) was estimated by using the Kaplan-Meier product-limit method , and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics . RESULTS On multivariate analysis , the MRI-assessed TRG ( mrTRG ) hazard ratios ( HRs ) were independently significant for survival ( HR , 4.40 ; 95 % CI , 1.65 to 11.7 ) and disease-free survival ( DFS ; HR , 3.28 ; 95 % CI , 1.22 to 8.80 ) . Five-year survival for poor mrTRG was 27 % versus 72 % ( P = .001 ) , and DFS for poor mrTRG was 31 % versus 64 % ( P = .007 ) . Preoperative MRI-predicted CRM independently predicted local recurrence ( LR ; HR , 4.25 ; 95 % CI , 1.45 to 12.51 ) . Five-year survival for poor post-treatment pathologic T stage ( ypT ) was 39 % versus 76 % ( P = .001 ) ; DFS for the same was 38 % versus 84 % ( P = .001 ) ; and LR for the same was 27 % versus 6 % ( P = .018 ) . The 5-year survival for involved pCRM was 30 % versus 59 % ( P = .001 ) ; DFS , 28 versus 62 % ( P = .02 ) ; and LR , 56 % versus 10 % ( P = .001 ) . Pathology node status did not predict outcomes . CONCLUSION MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery . Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome ABSTRACT Background Primary chemotherapy has been tested as a possible approach for patients with high risk features but predicted clear mesorectal margins on preoperative MRI assessment . This study investigates the prognostic relevance of baseline and post-treatment MRI and pathology staging in rectal cancer patients undergoing primary chemotherapy . Patients and methods Forty-six patients with T3 tumour > = 2 mm from the mesorectal fascia were prospect ively treated with Neoadjuvant Capecitabine , Oxaliplatin and Bevacizumab prior to surgery between 2009 and 2011 . The baseline and post-treatment MRI : T , Nodal and Extra-mural venous invasion ( EMVI ) status were recorded as well as post-treatment MRI Tumour regression grade ( TRG ) and modified-RECIST assessment of tumour length . The post-treatment pathology ( yp ) assessment s of T3 substage , N , EMVI and TRG status were also recorded . Three-year disease-free survival ( DFS ) and cumulative incidence of recurrence were estimated by using the Kaplan – Meier product-limit method , and Cox proportional hazards models were used to determine associations between staging and response on MRI and pathology with survival outcomes . Results About 46 patients underwent neoadjuvant chemotherapy alone for high risk margin safe primary rectal cancer . The median follow-up was 41 months , 5 patients died and 11 patients experienced relapse ( 2 local , 8 distant and 1 both ) . In total 23/46 patients were identified with MRI features of EMVI at baseline . mrEMVI positive status carried independent prognostic significance for DFS ( P = 0.0097 ) with a hazard ratio of 31.33 ( 95 % CI : 2.3–425.4 ) . The histopathologic factor that was of independent prognostic importance was a final ypT downstage of ypT3a or less , hazard ratio : 14.0 ( 95 % CI : 1.5–132.5 ) . Conclusions mrEMVI is an independent prognostic factor at baseline for poor outcomes in rectal cancer treated with neoadjuvant chemotherapy while ≤ypT3a is associated with an improvement in DFS . Future preoperative therapy evaluation in rectal cancer patients will need to stratify treatment according to baseline EMVI status as a crucial risk factor for recurrence in patients with predicted CRM clear rectal cancer Background : Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality , and to improve functional outcome . Methods : Locally advanced non-metastatic rectal cancers were identified from a prospect i ve data base . Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy ( CRT ) ( 50–54 Gy and 5-fluorouracil ) , and were reassessed 6–8 weeks post treatment . An active surveillance programme ( ‘ watch and wait ’ ) was offered to patients who were found to have a complete endoluminal response . Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm . Patients were followed up clinical ly , endoscopically and radiologically to assess for local recurrence or disease progression . Results : Of 785 patients with rectal cancer between 2005 and 2015 , 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT . Sixty out of three hundred and sixty-two ( 16.5 % ) patients were treated with organ-preserving strategies – 10 with ‘ watch and wait ’ and 50 by transanal excision . Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings . There was no significant difference in overall survival ( 85.6 % vs 93.3 % , P=0.414 ) or disease-free survival rate ( 78.3 % vs 80 % , P=0.846 ) when the outcomes of radical surgery were compared with organ preservation . Tumour regrowth occurred in 4 out of 45 ( 8.9 % ) patients who had organ preservation . Conclusions : Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT . Transanal excision defines the pathological response and refines decision-making |
11,266 | 25,037,577 | Most programs obtained some benefits over st and ard care in improving diabetes knowledge , self-management behaviors and clinical outcomes .
Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions , as well as in those involving peer educators , including cognitive reframing techniques , and a lower number of teaching methods .
The long-term effects remain unknown and cost-effectiveness was rarely estimated .
Conclusions Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior , ultimately improving glycemic control . | Background It is not clear to what extent educational programs aim ed at promoting diabetes self-management in ethnic minority groups are effective .
The aim of this work was to systematic ally review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes , and to identify programs ’ characteristics associated with greater success . | OBJECTIVE To test whether a theory-based , literacy , and culturally tailored self-management intervention , Latinos en Control , improves glycemic control among low-income Latinos with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 252 patients recruited from community health centers were r and omized to the Latinos en Control intervention or to usual care . The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge , attitudes , and self-management behaviors . The primary outcome was HbA1c . Secondary outcomes included diet , physical activity , blood glucose self-monitoring , diabetes knowledge and self-efficacy , and other physiological factors ( e.g. , lipids , blood pressure , and weight ) . Measures were collected at baseline and at 4- and 12-month follow-up . Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach . RESULTS A significant difference in HbA1c change between the groups was observed at 4 months ( intervention −0.88 [ −1.15 to −0.60 ] versus control −0.35 [ −0.62 to 0.07 ] , P < 0.01 ) , although this difference decreased and lost statistical significance at 12 months ( intervention −0.46 [ −0.77 to −0.13 ] versus control −0.20 [ −0.53 to 0.13 ] , P = 0.293 ) . The intervention result ed in significant change differences in diabetes knowledge at 12 months ( P = 0.001 ) , self-efficacy ( P = 0.001 ) , blood glucose self-monitoring ( P = 0.02 ) , and diet , including dietary quality ( P = 0.01 ) , kilocalories consumed ( P < 0.001 ) , percentage of fat ( P = 0.003 ) , and percentage of saturated fat ( P = 0.04 ) . These changes were in turn significantly associated with HbA1c change at 12 months . CONCLUSIONS Literacy-sensitive , culturally tailored interventions can improve diabetes control among low-income Latinos ; however , strategies to sustain improvements are needed BACKGROUND Type 2 diabetes is up to four times more common in British Asians , but they know little about its management and complications . AIM To design and evaluate a structured pictorial teaching programme for Pakistani Moslem patients in Manchester with type 2 diabetes . METHOD A r and omized controlled trial of pictorial flashcard one-to-one education in 201 patients attending a hospital outpatient clinic or diabetic clinics in ten general practice s in Manchester . Patients ' knowledge , self-caring skills and attitudes to diabetes were measured on four topics before the structured teaching , and compared with results six months later . RESULTS All parameters of knowledge were increased in the study group ; for example , percentage scores for correctly identifying different food values increased from 57 % to 71 % ( Analysis of Variance ( ANOVA ) adjusted difference + 11.8 % ) and knowledge of one diabetic complication from 18 % to 78 % . Self-caring behaviour improved , with 92 % of patients doing regular glucose tests at six months compared with 63 % at the start . Attitudinal views were more resistant to change , with patients still finding it hard to choose suitable foods at social occasions . Haemoglobin A1c control improved by 0.34 % over six months ( ANOVA adjusted difference , 95 % CI -0.8 % to + 0.1 % ) . CONCLUSION It is concluded that this health education programme can empower Asian diabetics to take control of their diets , learn to monitor and interpret glucose results , and underst and the implication s of poor glycaemic control for diabetic complications OBJECTIVES Diabetes self-management is a key element in the overall management of diabetes . Identifying barriers to disease self-management is a critical step in achieving optimal health outcomes . Our goal was to explore patients ' perceptions about barriers to self-management of diabetes that could possibly help explain poor health outcomes among minority patients . STUDY DESIGN Four focus groups were conducted among 31 predominately African American patients with diabetes who were enrolled in the Baltimore Cardiovascular Partnership Study , a NIH-funded multiyear prospect i ve partnership study . The topic guide consisted of a series of open-ended questions about knowledge of current health status , medication use , continuity of care , blood glucose level and nutrition . RESULTS The focus groups confirmed that previously reported barriers to self-management persisted and identified new concerns that could be associated with poor health outcomes among minority patients with diabetes . Attitudes , perceptions and behaviors surrounding diabetes and self-management of the condition did vary across individuals , however , the variation appeared to reflect the individual 's knowledge and opinions rather than patient 's age , sex , or culture . The primary barrier to diabetes self-management result ed from lack of knowledge of target blood glucose and blood pressure . Several participants found some of the health information to be quite confusing . CONCLUSIONS Diabetes is a major public health concern and the lack of awareness of target blood glucose and blood pressure further complicates the problem . The limited health literacy seen in this study could help explain several of the barriers to self-management . The barriers to self-management identified in this qualitative study are amenable to intervention that could improve health outcomes OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . METHODS One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit , Michigan , to participate in the Racial and Ethnic Approaches to Community Health ( REACH ) Detroit Partnership diabetes lifestyle intervention . The curriculum , delivered by trained community residents , was aim ed at improving dietary , physical activity , and diabetes self-care behaviors . Baseline and postintervention levels of diabetes-specific quality -of-life , diet , physical activity , self-care knowledge and behaviors , and hemoglobin A1C were assessed . RESULTS There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge . A statistically significant improvement in A1C level was achieved among REACH Detroit program participants ( P<.0001 ) compared with a group of patients with diabetes in the same health care system in which no significant changes were observed ( P=.160 ) . CONCLUSIONS A culturally tailored diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements Background : The prevalence of type 2 diabetes and diabetesrelated morbidity and mortality is higher among low-income Hispanics when compared to that of Whites . However , little is known about how to effectively promote self-management in this population . Purpose : The objectives were first to determine the feasibility of conducting a r and omized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects . Methods : Participants for this pilot study were recruited from a community health center , an elder program , and a community-wide data base developed by the community health center , in collaboration with other agencies serving the community , by surveying households in the entire community . Participants were r and omly assigned to an intervention ( n = 15 ) or a control ( n = 10 ) condition . Assessment s were conducted at baseline and at 3 months and 6 months postr and omization . The intervention consisted of 10 group sessions that targeted diabetes knowledge , attitudes , and self-management skills through culturally specific and literacysensitive strategies . The intervention used a cognitivebehavioral theoretical framework . Results : Recruitment rates at the community health center , elder program , and community registry were 48 % , 69 % , and 8 % , respectively . Completion rates for baseline , 3-month , and 6-month assessment s were 100 % , 92 % , and 92 % , respectively . Each intervention participant attended an average of 7.8 out of 10 sessions , and as a group the participants showed high adherence to intervention activities ( 93 % turned in daily logs , and 80 % self-monitored glucose levels at least daily ) . There was an overall Group × Time interaction ( p = .02 ) indicating group differences in glycosylated hemoglobin over time . The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was −0.8 % ( 95 % confidence intervals = −1.1 % , −0.5 % ) compared with the change in the control group ( p = .02 ) . At 6 months , the decrease in the intervention group remained significant , −0.85 % ( 95 % confidence intervals = −1.2 , −0.5 ) , and the decrease was still significantly different from that of the controls ( p = .005 ) . There was a trend toward increased physical activity in the intervention group as compared to that of the control group ( p = .11 ) and some evidence ( nonsignificant ) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants . Adjusting for baseline depressive scores , we oberved a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment ( p = .02 ) . Conclusions : Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research . This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a r and omized clinical trial PURPOSE The purpose of this r and omized controlled trial is to determine the effectiveness of an intervention led by promotoras ( community lay workers ) on the glycemic control , diabetes knowledge , and diabetes health beliefs of Mexican Americans with type 2 diabetes living in a major city on the Texas-Mexico border . METHODS One hundred fifty Mexican American participants were recruited at a Catholic faith-based clinic and r and omized into 2 groups . Personal characteristics , acculturation , baseline A1C level , diabetes knowledge , and diabetes health beliefs were measured . The intervention was culturally specific and consisted of participative group education , telephone contact , and follow-up using inspirational faith-based health behavior change postcards . The A1C levels , diabetes knowledge , and diabetes health beliefs were measured 3 and 6 months postbaseline , and the mean change between the groups was analyzed . RESULTS The 80 % female sample , with a mean age of 58 years , demonstrated low acculturation , income , education , health insurance coverage , and strong Catholicism . No significant changes were noted at the 3-month assessment , but the mean change of the A1C levels , F(1 , 148 ) = 10.28 , P < .001 , and the diabetes knowledge scores , F(1 , 148 ) = 9.0 , P < .002 , of the intervention group improved significantly at 6 months , adjusting for health insurance coverage . The health belief scores decreased in both groups . CONCLUSIONS The intervention result ed in decreased A1C levels and increased diabetes knowledge , suggesting that using promotoras as part of an interdisciplinary team can result in positive outcomes for Mexican Americans who have type 2 diabetes . Clinical implication s and recommendations for future research are suggested Background Latinos comprise the largest racial/ethnic group in the United States and have 2–3 times the prevalence of type 2 diabetes mellitus as Caucasians . Methods and design The Lawrence Latino Diabetes Prevention Project ( LLDPP ) is a community-based translational research study which aims to reduce the risk of diabetes among Latinos who have a ≥ 30 % probability of developing diabetes in the next 7.5 years per a predictive equation . The project was conducted in Lawrence , Massachusetts , a predominantly Caribbean-origin urban Latino community . Individuals were identified primarily from a community health center 's patient panel , screened for study eligibility , r and omized to either a usual care or a lifestyle intervention condition , and followed for one year . Like the efficacious Diabetes Prevention Program ( DPP ) , the LLDPP intervention targeted weight loss through dietary change and increased physical activity . However , unlike the DPP , the LLDPP intervention was less intensive , tailored to literacy needs and cultural preferences , and delivered in Spanish . The group format of the intervention ( 13 group sessions over 1 year ) was complemented by 3 individual home visits and was implemented by individuals from the community with training and supervision by a clinical research nutritionist and a behavioral psychologist . Study measures included demographics , Stern predictive equation components ( age , gender , ethnicity , fasting glucose , systolic blood pressure , HDL-cholesterol , body mass index , and family history of diabetes ) , glycosylated hemoglobin , dietary intake , physical activity , depressive symptoms , social support , quality of life , and medication use . Body weight was measured at baseline , 6-months , and one-year ; all other measures were assessed at baseline and one-year . All surveys were orally administered in Spanish . Results A community-academic partnership enabled the successful recruitment , intervention , and assessment of Latinos at risk of diabetes with a one-year study retention rate of 93%.Trial registration Poor adjustment to diabetes in older African American women may result from uncertainty , stemming from a lack of information about self-care activities , a complexity of self-care activities , comorbid conditions , and a lack of re sources . This study evaluated a telephone intervention to reduce uncertainty ( through problem-solving strategies , information , cognitive reframing , and improved patient — provider communication)—namely , to measure its effects on diabetes self-care and psychosocial adjustment . Sixty-eight older African American women were r and omly assigned to an experimental group and a control group . The experimental group received the intervention for 4 weeks , and the control group received usual care . Psychosocial adjustment and self-care were measured in all participants at baseline and 6 weeks postbaseline . The experimental group reported increased participation in exercise ( self-care component ; p < .001 ) and improvement in psychosocial adjustment ( p < .001 ) . Thus , reducing the uncertainty related to diabetes self-care improves self-care exercise , as well as psychosocial adjustment OBJECTIVE The objective of this study was to compare two diabetes self-management interventions design ed for Mexican Americans : " extended " ( 24 h of education , 28 h of support groups ) and " compressed " ( 16 h of education , 6 h of support groups ) . Both interventions were culturally competent regarding language , diet , social emphasis , family participation , and incorporating cultural beliefs . RESEARCH DESIGN AND METHODS We recruited 216 persons between 35 and 70 years of age diagnosed with type 2 diabetes > /=1 year . Intervention groups of eight participants and eight support persons were r and omly assigned to the compressed or extended conditions . The interventions differed in total number of contact hours over the year-long intervention period , with the major difference being the number of support group sessions held . The same information provided in the educational sessions of the extended intervention was compressed into fewer sessions , thus providing more information during each group meeting . RESULTS The interventions were not statistically different in reducing HbA(1c ) ; however , both were effective . A " dosage effect " of attendance was detected with the largest HbA(1c ) reductions achieved by those who attended more of the extended intervention . For individuals who attended > /=50 % of the intervention , baseline to 12-month HbA(1c ) change was -0.6 percentage points for the compressed group and -1.7 percentage points for the extended group . CONCLUSIONS Both culturally competent diabetes self-management education interventions were effective in promoting improved metabolic control and diabetes knowledge . A dosage effect was evident ; attending more sessions result ed in greater improvements in metabolic control BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED OBJECTIVE To determine whether a culturally appropriate clinic- and community-based intervention for African-American women with type 2 diabetes will increase moderate-intensity physical activity ( PA ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial conducted at seven practice s in central North Carolina , 200 African-American women , > or = 40 years of age with type 2 diabetes , were r and omized to one of three treatment conditions : clinic and community ( group A ) , clinic only ( group B ) , or minimal intervention ( group C ) . The clinic-based intervention ( groups A and B ) consisted of four monthly visits with a nutritionist who provided counseling to enhance PA and dietary intake that was tailored to baseline practice s and attitudes ; the community-based intervention ( group A ) consisted of three group sessions and 12 monthly phone calls from a peer counselor and was design ed to provide social support and reinforce behavior change goals ; and the minimal intervention ( group C ) consisted of educational pamphlets mailed to participants . The primary study outcome was the comparison of PA levels between groups assessed at 6 and 12 months by accelerometer , which was worn while awake for 7 days . RESULTS Totals of 175 ( 88 % ) and 167 ( 84 % ) participants completed PA assessment at 6 and 12 months , respectively . For comparison of PA , the P value for overall group effect was 0.014 . Comparing group A with C , the difference in the average adjusted mean for PA was 44.1 kcal/day ( 95 % CI 13.1 - 75.1 , P = 0.0055 ) . Comparing group B with C , the difference in the average adjusted mean was 33.1 kcal/day ( 95 % CI 3.3 - 62.8 , P = 0.029 ) . The intervention was acceptable to participants : 88 % were very satisfied with clinic-based counseling to enhance PA , and 86 % indicated that the peer counselor 's role in the program was important . CONCLUSIONS The intervention was associated with a modest enhancement of PA and was acceptable to participants Abstract Objectives . To test the efficacy of a simple intervention method to reduce risk factors for type 2 diabetes ( DM ) and cardiovascular disease ( CVD ) in Alaskan Eskimos . Study Design . The study consisted of 1 ) a comprehensive screening for risk factors of 454 individuals in 4 villages , 2 ) a 4-year intervention and 3 ) a repetition of the screening in year 5 to test the efficacy of the intervention . Methods . Personal counseling ( 1hr/year ) stressed the consumption of more traditional foods high in ɷ-3 fatty acids and less of certain specific store-bought foods high in palmitic acid , which was identified as being associated with glucose intolerance . Results . The intervention result ed in significant reductions in plasma concentrations of total cholesterol ( p = 0.0001 ) , LDL cholesterol ( p = 0.0001 ) , fasting glucose ( p = 0.0001 ) , diastolic blood pressure ( p = 0.0007 ) and improved glucose tolerance ( p = 0.0006 ) . This occurred without loss of body weight . Sixty percent of the participants had improved glucose tolerance ; only one of the 44 originally identified with impaired glucose tolerance ( IGT ) developed DM during the study . Conclusions . Dramatic improvements of risk factors for DM and CVD were achieved in the intervention by primarily stressing the need for changes in the consumption of specific fats . The results suggest that fat consumption is an important risk factor for DM . ( Int J Circumpolar Health 2005 ; 64(4):409–424 OBJECTIVE To compare the effectiveness of a telephonic and a print intervention over 1 year to improve diabetes control in low-income urban adults . RESEARCH DESIGN AND METHODS A r and omized trial in Spanish and English comparing a telephonic intervention implemented by health educators with a print intervention . Participants ( N = 526 ) had an A1C ≥7.5 % and were prescribed one or more oral agents . All were members of a union/employer jointly sponsored health benefit plan . Health coverage included medications . Primary outcomes were A1C and pharmacy cl aims data ; secondary outcomes included self-report of two medication adherence measures and other self-care behaviors . RESULTS Participants were 62 % black and 23 % Hispanic ; 77 % were foreign born , and 42 % had annual family incomes < $ 30 thous and . Baseline median A1C was 8.6 % ( interquartile range 8.0–10.0 ) . Insulin was also prescribed for 24 % of participants . The telephone group had mean ± SE decline in A1C of 0.23 ± 0.11 % over 1 year compared with a rise of 0.13 ± 0.13 % for the print group ( P = 0.04 ) . After adjusting for baseline A1C , sex , age , and insulin use , the difference in A1C was 0.40 % ( 95 % CI 0.10–0.70 , P = 0.009 ) . Change in medication adherence measured by cl aims data , but not by self-report measures , was significantly associated with change in A1C ( P = 0.01 ) . Improvement in medication adherence was associated ( P = 0.005 ) with the telephonic intervention , but only among those not taking insulin . No diabetes self-care activities were significantly correlated with the change in A1C . CONCLUSIONS A 1-year tailored telephonic intervention implemented by health educators was successful in significantly , albeit modestly , improving diabetes control compared with a print intervention in a low-income , insured , minority population OBJECTIVE To conduct a 1-year r and omized clinical trial to evaluate a remote comprehensive diabetes self-management education ( DSME ) intervention , Diabetes TeleCare , administered by a dietitian and nurse/certified diabetes educator ( CDE ) in the setting of a federally qualified health center ( FQHC ) in rural South Carolina . RESEARCH DESIGN AND METHODS Participants were recruited from three member health centers of an FQHC and were r and omized to either Diabetes TeleCare , a 12-month , 13-session curriculum delivered using telehealth strategies , or usual care . RESULTS Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin ( GHb ) in the Diabetes TeleCare group from baseline to 6 and 12 months ( 9.4 ± 0.3 , 8.3 ± 0.3 , and 8.2 ± 0.4 , respectively ) compared with usual care ( 8.8 ± 0.3 , 8.6 ± 0.3 , and 8.6 ± 0.3 , respectively ) . LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care . Although not part of the original study design , GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group ( 9.2 ± 0.4 , 7.4 ± 0.5 , and 7.6 ± 0.5 , respectively ) compared with usual care ( 8.7 ± 0.4 , 8.1 ± 0.4 , and 8.1 ± 0.5 , respectively ) in a post hoc analysis of a subset of the r and omized sample who completed a 24-month follow-up visit . CONCLUSIONS Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index Introduction Diabetes Mellitus is a chronic illness that increases the risk of microvascular complication and results in blindness , kidney failure , and lower extremity amputations , and macrovascular complication of coronary artery disease and stroke . In the State of Hawaii , an estimated eight to ten percent of the population have diabetes mellitus , i.e. about 80,000 to 100,000 individuals , primarily adults with type 2 diabetes . Alarmingly , native Hawaiian adults over 30 years of age have been identified with a diabetes prevalence rate of 20 % . Several studies clearly document the increasing rate of diabe tes among native Hawaiians over the past 30 years . Based on recent data , it is estimated that about 20,000 adult native Hawaiians ( 1820 % prevalence rate ) have diabetes mellitus ) It would appear that interventions to prevent diabetes and diabetic complications receive the highest priority in the effort to improve the health status of the people of Hawaii , especially native Hawaiians . Two major intervention trials have clearly demonstrated that intensive glycemic control prevents and delays the development of microvascular complication in patients with type 1 diabetes : the Diabetes Control and Complications Trial ( DCCT ) and the Stockholm Diabetes Intervention Study ( SDIS ) . 23 Results from a r and omized prospect i ve 6-year study in Japan show that intensive insulin treat ment of type 2 diabetic patients reduces microvascular complica tion . 4Many studies have demonstrated the association of hypergly cemia with macrovascular complications of ischemic heart disease and stroke and increased cardiovascular disease risk factors , e.g. , dyslipidemia , hypertension , and obesity . The 12-year cardiovascu lar mortality of men screened in the Multiple Risk Factor Interven tion Trial ( MRFIT ) showed that diabetic patients consistently had higher cardiovascular mortality than non-diabetic men matched for one or more of the major risk factors for CVD . 5 The data from Background Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin . Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population . The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes . We then investigated whether this intervention could produce an improvement , and finally whether any improvement was greater than background changes in knowledge in comparison groups . Methods A multi-site prospect i ve , r and omised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow , Scotl and . The intervention consisted of 18 educational sessions in 6 separate programmes . A modified question naire was used to measure the knowledge , attitudes , and practice of diabetes before and after intervention . Results Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes , regarded the disease less seriously , and had a lesser underst and ing of the relationship between control and complications than the white population . No differences in initial responses were found between those who completed the second assessment and those who did not . The intervention group showed significant improvements in scores for Knowledge ( + 12.5 % ) ; Attitudes toward seriousness ( + 13.5 % ) , complications ( + 8.1 % ) , Practice ( + 20.0 % ) . However there were also changes in the ethnic control group scores ; respectively + 5.0 % , + 16.3 % ( significant P < 0.001 ) , + 1.5 % , + 1.7 % . The single white control group also showed some improvements ; respectively + 12.2 % , + 12.4 % ( P = 0.04 ) , + 6.0 % , + 25.0 % ( P = 0.007 ) , but the differences in improvement between these two control groups were not significant . Overall , the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change ( P = 0.36 CI -0.9 to + 2.6 ) . Conclusion This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice . However there was no net benefit compared with the control group OBJECTIVE To compare a peer leader ( PL ) versus a community health worker ( CHW ) telephone outreach intervention in sustaining improvements in HbA1c over 12 months after a 6-month diabetes self-management education ( DSME ) program . RESEARCH DESIGN AND METHODS One hundred and sixteen Latino adults with type 2 diabetes were recruited from a federally qualified health center and r and omized to 1 ) a 6-month DSME program followed by 12 months of weekly group sessions delivered by PLs with telephone outreach to those unable to attend or 2 ) a 6-month DSME program followed by 12 months of monthly telephone outreach delivered by CHWs . The primary outcome was HbA1c . Secondary outcomes were cardiovascular disease risk factors , diabetes distress , and diabetes social support . Assessment s were conducted at baseline , 6 , 12 , and 18 months . RESULTS After DSME , the PL group achieved a reduction in mean HbA1c ( 8.2–7.5 % or 66–58 mmol/mol , P < 0.0001 ) that was maintained at 18 months ( −0.6 % or −6.6 mmol/mol from baseline [ P = 0.009 ] ) . The CHW group also showed a reduction in HbA1c ( 7.8 vs. 7.3 % or 62 vs. 56 mmol/mol , P = 0.0004 ) post–6 month DSME ; however , it was attenuated at 18 months ( −0.3 % or −3.3 mmol/mol from baseline , within-group P = 0.234 ) . Only the PL group maintained improvements achieved in blood pressure at 18 months . At the 18-month follow-up , both groups maintained improvements in waist circumference , diabetes support , and diabetes distress , with no significant differences between groups . CONCLUSIONS Both low-cost maintenance programs led by either a PL or a CHW maintained improvements in key patient-reported diabetes outcomes , but the PL intervention may have additional benefit in sustaining clinical improvements beyond 12 months OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life Background Type 2 diabetes ( diabetes ) is a serious threat to public health in the United States and disproportionally affects many racial/ethnic minority groups , including African Americans . Limited access to treatment and high attrition rates further contribute to health disparities in diabetes-related morbidity and mortality among minorities . Greater opportunities for increasing access and decreasing barriers to treatment are needed . Technology-based interventions have potential for accomplishing this goal but evidence of feasibility and potential effectiveness is lacking , especially for population s that traditionally have limited educational attainment and low computer literacy . Objective This paper describes the design and methods of a pilot r and omized clinical trial that will compare the feasibility and potential efficacy of delivering a diabetes self-management intervention via a virtual world vs. a face-to-face format . Methods Study participants ( n=100 ) will be African American women with uncontrolled type 2 diabetes recruited from primary care practice s and affiliated health centers at a large safety net hospital in Massachusetts . Participants will be r and omized into a virtual world-based ( VW ) intervention condition or a face-to-face control condition . Both conditions provide the same theory-based curriculum and equivalent exposure to the self-management program ( eight group sessions ) , and both will be delivered by a single intervention team ( a dietitian and a diabetes educator ) . Assessment s will be conducted at baseline and 4 months . Feasibility will be determined by evaluating the degree to which participants engage in the VW-based intervention compared to face to face ( number of sessions completed ) . Potential efficacy will be determined by comparing change in physiological ( glycemic control ) and behavioral ( self-reported dietary intake , physical activity , blood glucose self-monitoring , and medication adherence ) outcomes between the experimental and control groups . Results The primary outcomes of interest are feasibility of the VW intervention and its potential efficacy on glucose control and diabetes self-management behaviors , compared to the face-to-face condition . Analysis will use a two- sample Kolmogorov-Smirnov test for changes in variable distribution . P values will be calculated using binomial tests for proportions and t tests for continuous variables . Conclusions If the intervention is found to be feasible and promising , it will be tested in a larger RCT OBJECTIVE To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , repeated measures study was conducted on the Texas-Mexico border in Starr County . A total of 256 r and omly selected individuals with type 2 diabetes between 35 and 70 years of age , diagnosed with type 2 diabetes after 35 years of age , and accompanied by a family member or friend were included . The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses , dietitians , and community workers . The intervention involved 3 months of weekly instructional sessions on nutrition , self-monitoring of blood glucose , exercise , and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes . The approach was culturally competent in terms of language , diet , social emphasis , family participation , and incorporation of cultural health beliefs . Outcomes included indicators of metabolic control ( HbA(1c ) and fasting blood glucose ) , diabetes knowledge , and diabetes-related health beliefs . RESULTS Experimental groups showed significantly lower levels of HbA(1c ) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores . At 6 months , the mean HbA(1c ) of the experimental subjects was 1.4 % below the mean of the control group ; however , the mean level of the experimental subjects was still high ( > 10 % ) . CONCLUSIONS This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans , particularly for those individuals with HbA(1c ) levels > 10 % Participants who received Pies Sanos , a 15-min intervention design ed to improve diabetes self-efficacy and foot self-care behaviors in adult patients with type 2 diabetes who lived in a predominantly Mexican American community , performed more-complete foot self-care 1 month later in their homes . Recruited when they presented for nonurgent care to the emergency department in two community hospitals near the U.S .— Mexico border , participants were r and omized into one of three groups . At follow-up , there was a significant difference in observed foot self-care behaviors between groups , F(2 , 135 ) = 2.99 , p < .05 , as well as a significant difference within the intervention , t ( 47 ) = −4.32 , p < .01 , and control group , t ( 46 ) = −2.06 , p < .05 , for baseline and follow-up self-reported foot self-care behaviors . Baseline diabetes self-efficacy was significantly and positively correlated with both baseline ( r = .335 , p < .001 ) and follow-up ( r = .174 , p < .05 ) foot self-care behaviors OBJECTIVE To evaluate a weight loss and exercise program design ed to improve diabetes management in older African-Americans . RESEARCH DESIGN AND METHODS Overweight African-Americans ( n = 64 ) ages 55–79 years with NIDDM were r and omized to either an intervention ( 12 weekly group sessions , 1 individual session , and 6 biweekly group sessions ) or usual care ( 1 class and 2 informational mailings ) . Clinical and behavioral variables were assessed at 0 , 3 , and 6 months of treatment . RESULTS Significant net differences in the intervention versus usual care were observed for weight ( −2.0 kg , P = 0.006 ) , physical activity , and dietary intake of fat , saturated fat , cholesterol , and nutrition knowledge at 3 months ( all P < 0.05 ) and for weight at 6 months ( −2.4 kg ; P = 0.006 ) and mean HbA1c values at 3 and 6 months ( respectively , −1.6 and −2.4 % , both P < 0.01 ) . After the adjustment for changes in weight and activity , the intervention participants were ∼ twice as likely to have a one unit decrease in HbA1c value as those in usual care . Blood pressure increase sin usual care participants result ed in net differences ( intervention minus control ) at 3 and 6 months of −3.3 ( P = 0.09 ) and −4.0 ( P = 0.05 ) mmHg diastolic , respectively , and −8.4 ( P = 0.06 ) and −5.9 ( P > 0.10 ) mmHg systolic , respectively . Blood lipid profiles improved more in intervention than usual care participants , but not significantly . CONCLUSIONS The intervention program was effective in improving glycemic and blood pressure control . The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake , weight , and activity and may reflect indirect program effects on other aspects of self-care OBJECTIVE The objective of this study was to evaluate the impact of a problem-based empowerment patient education program specifically tailored for urban African Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS The study used a r and omized controlled trial ( RCT ) pretest/post-test design with repeated measures . Patients were r and omly assigned to either a six-week intervention group or a six-week wait-listed control group . After completing the six sessions , patients were invited to participate in one of two follow-up conditions ; attend a monthly support group or receive a monthly phone call from a nurse . Assessment measures included HbA1C , lipids , blood pressure , weight , self-management behavior and psychosocial adaptation . RESULTS Both control and intervention patients showed a broad array of small-to-modest positive changes during the six-week RCT . These gains were maintained or improved upon during the one-year follow-up period . For patients in the two follow-up conditions , a positive correlation was seen between the number of follow-up contacts and their one-year HbA1C values . CONCLUSIONS We believe that results of this study can be attributed to volunteer bias , study effects ( ie , providing study data on several occasions to patients and their physicians during the one-year study period ) , and impact of the interventions . However , the study design does not allow us to examine the relative impact of these three factors on the patient improvements seen over the one-year study period Background : Type 2 diabetes affects one in five African American women older than 60 years . These women face distinct challenges in managing diabetes self-care . Therefore , tailored self-care interventions for this population need to be developed and tested . Objectives : The effectiveness of a tailored , four-visit , in-home symptom-focused diabetes intervention with and without booster telephone calls was compared with an attentional control focused on skills training for weight management and diet . Methods : African American women ( n = 180 ; > 55 years old , Type 2 diabetes mellitus > 1 year , HbA1c > 7 % ) were r and omly assigned to the intervention or attentional control condition . Half the intervention participants were assigned to also receive a telephone-delivered booster intervention . Participants were evaluated at baseline and 3 , 6 , and 9 months . Results : Baseline HbA1 was 8.3 in the intervention group ( n = 60 ) , 8.29 in the intervention with booster group ( n = 55 ) , and 8.44 in the attentional control condition ( n = 59 ) . HbA1c declined significantly in the whole sample ( 0.57 % ) with no differences between study arms . Participants in the booster arm decreased HbA1c by 0.76 % . Symptom distress , perceived quality of life , impact of diabetes , and self-care activities also improved significantly for the whole sample with no significant differences between study arms . Discussion : Parsimonious interventions of four in-person visits yielded clinical ly significant decreases in HbA1c . Although the weight and diet program was intended as an attentional control , the positive effects suggest it met a need in this population . Because the contents of both the intervention and the attentional control were effective despite different approaches , a revised symptom-focused intervention that incorporates weight and diet skills training may offer even better results BACKGROUND Compared with white persons , African Americans have a greater incidence of diabetes , decreased control , and higher rates of microvascular complications . A peer mentorship model could be a scalable approach to improving control in this population and reducing disparities in diabetic outcomes . OBJECTIVE To determine whether peer mentors or financial incentives are superior to usual care in helping African American veterans decrease their hemoglobin A(1c ) ( HbA(1c ) ) levels . DESIGN A 6-month r and omized , controlled trial . ( Clinical Trials.gov registration number : NCT01125956 ) SETTING Philadelphia Veterans Affairs Medical Center . PATIENTS African American veterans aged 50 to 70 years with persistently poor diabetes control . INTERVENTION 118 patients were r and omly assigned to 1 of 3 groups : usual care , a peer mentoring group , and a financial incentives group . Usual care patients were notified of their starting HbA(1c ) level and recommended goals for HbA(1c ) . Those in the peer mentoring group were assigned a mentor who formerly had poor glycemic control but now had good control ( HbA(1c ) level ≤7.5 % ) . The mentor was asked to talk with the patient at least once per week . Peer mentors were matched by race , sex , and age . Patients in the financial incentive group could earn $ 100 by decreasing their HbA(1c ) level by 1 % and $ 200 by decreasing it by 2 % or to an HbA(1c ) level of 6.5 % . MEASUREMENTS Change in HbA(1c ) level at 6 months . RESULTS Mentors and mentees talked the most in the first month ( mean calls , 4 ; range , 0 to 30 ) , but calls decreased to a mean of 2 calls ( range , 0 to 10 ) by the sixth month . Levels of HbA(1c ) decreased from 9.9 % to 9.8 % in the control group , from 9.8 % to 8.7 % in the peer mentor group , and from 9.5 % to 9.1 % in the financial incentive group . Mean change in HbA(1c ) level from baseline to 6 months relative to control was -1.07 % ( 95 % CI , -1.84 % to -0.31 % ) in the peer mentor group and -0.45 % ( CI , -1.23 % to 0.32 % ) in the financial incentive group . LIMITATION The study included only veterans and lasted only 6 months . CONCLUSION Peer mentorship improved glucose control in a cohort of African American veterans with diabetes . PRIMARY FUNDING SOURCE National Institute on Aging Roybal Center Latinas with type 2 diabetes are in need of culturally sensitive interventions to make recommended long-term lifestyle changes and reduce heart disease risk . To test the longer-term ( 24-month ) effects of a previously successful , culturally adapted , multiple-health-behavior-change program , ¡ Viva Bien ! , 280 Latinas were r and omly assigned to usual care or ¡ Viva Bien!. Treatment included group meetings to promote a culturally adapted Mediterranean diet , physical activity , supportive re sources , problem solving , stress-management practice s , and smoking cessation . ¡ Viva Bien ! participants achieved and maintained some lifestyle improvements from baseline through 24 months , including significant improvements for psychosocial outcomes , fat intake , social – environmental support , body mass index , and hemoglobin A1c . Effects tended to diminish over time . The ¡ Viva Bien ! multiple-behavior program was effective in improving and maintaining some psychosocial , behavioral , and biological outcomes related to heart health across 24 months for Latinas with type 2 diabetes , a high-risk , underserved population ( Clinical Trials.gov number , NCT00233259 ) This article reports on the development and pilot feasibility testing of a culturally competent intervention of education and care for black women with type 2 diabetes mellitus ( T2DM ) . Using a one group , pretest posttest quasi-experimental design , the intervention was tested with a convenience sample of 25 community black women with T2DM . The conceptual basis , process , and content of the intervention as well as the feasibility and acceptability of study material s and methods are described . Significant improvements from baseline to 3 months were observed in measures of glycemic control , weight , body mass index , and diabetes-related emotional distress . The findings suggest that a culturally sensitive intervention of nurse practitioner diabetes care and education is beneficial for black women with T2DM , result ing in program attendance , kept appointments , improved glycemic control and weight , and decreased diabetes-related emotional distress Two objectives were established for this study : 1 ) to assess the impact of a culturally specific , intensive diabetes education program on dietary patterns , and 2 ) to assess nutrient consumption relative to the Recommended Dietary Allowances . The study population consisted of elderly Mexican Americans with diabetes living in Harlingen and Brownsville , Texas . The experimental group ( n=78 ) participated in an intense , 2-hour nutrition education session , while the control group ( n=74 ) did not . The education session was conducted for groups of eight subjects via videotapes and interactive discussion . All groups experienced significant weight loss except the women in the experimental group . After the education program , however , the experimental women had increased the percentage of calories consumed daily from carbohydrate . Mean calcium consumption was substantially less than the RDA in all groups , and inadequate amounts of ascorbic acid and vitamin A often were consumed . Intensive , frequent , long-term follow-up appears essential for more sustained results The purpose of this study was to determine the feasibility of providing a diabetes patient education and group-support intervention that was directed by a Mexican-American clinical nurse specialist ( CNS ) , dietitian , and community worker ; consistent with national st and ards ; and design ed for the Mexican-American culture . In a rural Texas-Mexico border community , subjects with diabetes were r and omly selected to participate in the intervention , and a family member of each subject participated as a support person . The intervention involved 8 weeks of educational sessions with instruction on nutrition , blobd glucose self-monitoring , exercise , and other diabetes self-management topics , and provided group support . Group discussion was facilitated using a series of Spanish- language videotapes that had been developed and previously tested in the target Mexican-American community . Results suggested statistically significant improvements in diabetes knowledge , fasting blood sugar levels , and glycosylated hemoglobin levels . The study documented the feasibility and potential benefits of the intervention OBJECTIVES We evaluated lifestyle interventions for diabetic persons who live in rural communities . METHODS We conducted a 12-month r and omized clinical trial ( n = 152 ) of " intensive-lifestyle " ( modeled after the NIH Diabetes Prevention Program ) and " reimbursable-lifestyle " ( intensive-lifestyle intervention delivered in the time allotted for Medicare reimbursement for diabetes education related to nutrition and physical activity ) interventions with usual care as a control . RESULTS Modest weight loss occurred by 6 months among intensive-lifestyle participants and was greater than the weight loss among usual-care participants ( 2.6 kg vs 0.4 kg , P<.01 ) . At 12 months , a greater proportion of intensive-lifestyle participants had lost 2 kg or more than usual-care participants ( 49 % vs 25 % , P<.05 ) . No differences in weight change were observed between reimbursable-lifestyle and usual-care participants . Glycated hemoglobin was reduced among all groups ( P<.05 ) but was not different between groups . CONCLUSIONS Improvement in both weight and glycemia was attainable by lifestyle interventions design ed for persons who had type 2 diabetes and lived in rural communities OBJECTIVES This study evaluated a multicomponent educational intervention to increase ophthalmic examination rates among African Americans with diabetes . METHODS A r and omized trial was conducted with 280 African Americans with diabetes , enrolled from outpatient departments of 5 medical centers in the New York City metropolitan area , who had not had a dilated retinal examination within 14 months of r and omization ( 65.7 % female , mean age = 54.7 years [ SD = 12.8 years ] ) . RESULTS After site differences were controlled , the odds ratio for receiving a retinal examination associated with the intervention was 4.3 ( 95 % confidence interval = 2.4 , 7.8 ) . The examination rate pooled across sites was 54.7 % in the intervention group and 27.3 % in the control group . CONCLUSIONS The intervention was associated with a rate of ophthalmic examination double the rate achieved with routine medical care A culturally sensitive 3-month intervention was provided to 18 Caribbean Latino men and women with non-insulin-dependent ( type 2 ) diabetes mellitus . Compared to the r and omly assigned control group , the intervention group showed statistically significant decreases in total calories , fat calories , percent of calories from fat , saturated fat calories , and percent of calories from saturated fat The intervention group showed increases in calories from carbohydrates and in the percent of calories from fiber Purpose The purpose of this study was to evaluate the impact of an innovative intervention that utilized a certified medical assistant with specific diabetes training to work with a multidisciplinary diabetes care team to help provide basic diabetes education and self-care support in low-income minority population s with type 2 diabetes . Methods Enrolled participants were r and omized to either the medical assistant coaching ( MAC ) group ( N = 25 ) or the treatment as usual ( TAU ) group ( N = 25 ) . Deidentified data was obtained on a matched no contact control ( NCC ) group ( N = 50 ) . Results Analysis of covariance ( ANCOVA ) comparisons revealed no significant differences between the 3 groups on A1C , but a trend was observed . A1Cs decreased across time for the MAC group , while increasing for the TAU and NCC groups . ANCOVA comparisons also indicated that the MAC group experienced significantly greater increases in perceived empowerment and a larger , although non-significant , reduction in perceived diabetes related problems than the TAU group . Conclusions This r and omized controlled pilot study suggests that the inclusion of a medical assistant self-care coach as part of the diabetes care team holds promise in improving outcomes and should be further examined in a large-scale study |
11,267 | 24,847,100 | CONCLUSIONS P300 amplitude was smaller in cigarette smokers than in nonsmoking controls , and a possible dose-response relationship was apparent .
Findings indicate a possible association between cigarette smoking and decreased P300 amplitude | OBJECTIVE To determine the association between chronic tobacco cigarette smoking and P300 amplitude . | This study examined the effects of abstinence from smoking , of smoking history , and of nicotine administration on visual attention ( 2-Letter Search Task ) , verbal information processing ( Logical Reasoning Task ) , and working memory ( N-Back Tasks ) . Fourteen smokers , 15 ex-smokers , and 9 never-smokers took part . All subjects participated in a training session ( when smokers had been smoking ad libitum ) and in two subsequent test sessions after administration of 4 mg nicotine gum or placebo , respectively . Smokers were 12-h abstinent when they received gum . An effect of acute nicotine administration ( independent of smoking history ) was seen only with respect to reaction time on the 2-Letter Search Task . Working memory performance was related to smoking history ( smokers performed most poorly and never-smokers best ) . The Logical Reasoning Task showed no effects of either acute or chronic nicotine exposure . The findings indicate that nicotine may influence focusing of attention in smokers as well as nonsmokers , and that trait-like differences in some cognitive domains , such as working memory , may be either long-term effects or etiological factors related to smoking In the elderly , cigarette smoking has been related to reduced cognitive performance and moderate alcohol consumption to increased cognitive performance . It is not clear whether these associations also exist in middle age . The authors examined these relations in a population -based cohort study of 1,927 r and omly selected , predominantly middle-aged subjects aged 45 - 70 years at the time of cognitive testing and living in the Netherl and s. From 1995 until 2000 , an extensive cognitive battery was administered , and compound scores were calculated . Risk factors had been assessed approximately 5 years previously . Multiple linear regression analyses ( in which one unit of the cognitive score = one st and ard deviation ) showed that , after the authors adjusted for age , sex , education , alcohol consumption , and cardiovascular risk factors , current smokers had reduced psychomotor speed ( beta = -0.159 , 95 % confidence interval : -0.071 , -0.244 ; p = 0.0003 ) and reduced cognitive flexibility ( beta = -0.133 , 95 % confidence interval : -0.035 , -0.230 ; p = 0.008 ) compared with never smokers . This effect was similar to that of being approximately 4 years older . Alcohol consumption was related to increased speed and better flexibility , especially among women who drank 1 - 4 alcoholic beverages a day . In conclusion , among middle-aged subjects , current smoking was inversely and alcohol consumption positively related to psychomotor speed and cognitive flexibility . This finding suggests that actions to prevent cognitive decline can be taken in middle age Auditory P300 latency prolongation or amplitude reduction has been reported in patients affected by bipolar disorder and in schizophrenia . The purpose of this study was to test whether the auditory P300 and earlier event-related potential ( ERP ) components elicited during an auditory discrimination task could differentiate between these two disorders . Thirteen patients with manic or mixed bipolar disorder , 12 patients with schizophrenia , and 24 control subjects were evaluated . None of the subjects had a history of alcohol or substance abuse or dependence . ERPs were elicited during an auditory discrimination task in which a subject pressed a key to infrequent 1500 Hz tones interspersed amid a series of 1000 Hz tones . The amplitude and latency of N100 and P200 were measured from ERPs to non-target tones , and N200 and P300 were measured from ERPs to target tones . N100 , P200 and N200 amplitudes were reduced in schizophrenia patients , but not in bipolar patients . Both bipolar disorder and schizophrenia patients showed reduced P300 amplitude and prolonged P300 latency . Amplitude reduction in the early ERP components implicates auditory processing deficits in schizophrenia . Both groups showed reductions in P300 amplitude , suggesting a disturbance of the temporal-parietal generators of this component . Prolonged P300 latency is consistent with impaired attentional processing in schizophrenia and symptomatic bipolar disorder patients Numerous studies have evaluated event-related potentials ( ERPs ) as biological indicators of the liability for alcoholism . This study extends that approach by investigating ERPs in boys at risk for other substance use disorders . Prepubertal ( 10 - 12 years ) sons of fathers diagnosed with psychoactive substance dependence ( n = 28 ) were compared to matched sons of nonaffected fathers ( n = 26 ) on an auditory ERP oddball task . Multivariate analyses of variance applied to peak amplitude and latency measures indicated small to moderate between-groups differences at midline or parietal sites : N2 and P3 amplitude ; P2 , N2 , P3 , and Nc latency . This replicated P3 amplitude findings in alcoholism-risk studies , though the effect size was moderate . Analysis of event-related alpha power indicated significantly longer latency of alpha synchronization and oscillations of desynchronization in boys at risk . The alpha power findings were statistically the more robust of the measures applied . The role of neurocognitive factors in determining liability for substance use disorders is discussed A 21-mg dose of nicotine was administered transdermally to 16 overnight smoking-deprived smokers in a double-blind , placebo-controlled design . Mood ratings , electroencephalography ( EEG ) , behavioral performance and event-related potential ( ERP : P300 ) indices of attention and information processing speed were assessed before and 4 h after placebo/nicotine treatment . Although nicotine , relative to placebo , failed to alter mood , it increased absolute and relative power indices of EEG arousal , shortened reaction times , and increased P300 amplitudes . The results are discussed in relation to nicotine 's actions on cholinergic transmission and its role in smoking behavior BACKGROUND Previous studies suggested a protective effect of smoking on Alzheimer 's disease , but most were case-control studies based on prevalent cases . The findings of prospect i ve studies on the association between smoking and the risk of dementia are inconclusive . METHODS We did a population -based follow-up study of elderly people who were initially free of dementia . 6870 people aged 55 years and older agreed to take part . Smoking history was taken at baseline and participants were classified as never smokers , former smokers , and current smokers . During follow-up , we recorded all incident cases of dementia . We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer 's disease by Cox proportional hazards regression , after adjustment for age , sex , education , and alcohol intake . We also examined modification of risk by age , sex , and the apolipoprotein E ( APOE ) genotype . FINDINGS During mean follow-up of 2.1 ( range 1.5 - 3.4 ) years , 146 incident cases of dementia were detected , of which 105 were Alzheimer 's disease . Compared with never smokers , smokers had an increased risk of dementia ( relative risk 2.2 [ 95 % CI 1.3 - 3.6 ] ) and Alzheimer 's disease ( 2.3 [ 1.3 - 4.1 ] ) . Smoking was a strong risk factor for Alzheimer 's disease in individuals without the APOEepsilon4 allele ( 4.6 [ 1.5 - 14.2 ] ) , but had no effect in participants with this allele ( 0.6 [ 0.1 - 4.8 ] ) . INTERPRETATION Smoking was associated with a doubling of the risk of dementia and Alzheimer 's disease . Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer 's disease OBJECTIVES Early diagnosis and monitoring of disease progression have become vital in clinical practice as disease modifying treatments for Alzheimer 's disease ( AD ) become available . This one-year prospect i ve study aim ed to clarify the usefulness of event-related potentials ( ERPs ) in cognitive decline and eluci date their cognitive significance in AD . METHODS Using the Cognitive Abilities Screening Instrument ( CASI ) and ERPs , probable AD patients , mild cognitive impairment ( MCI ) patients , and normal controls were recruited . RESULTS The AD and MCI patients had significantly decreased cognitive function and manifested a delay of P300 latency . The P300 latencies demonstrated significantly more prolongation than their baseline values in probable AD and MCI patients , although their CASI scores showed no statistically significant decline . Whereas N100 , P200 , and N200 components did not reach statistical differences between groups either in the baseline or follow-up assessment s and did not show significant change on follow-up . CONCLUSION The combination of neuropsychological tests and P300 measurements proved useful in improving reliability and increasing sensitivity to early cognitive decline or disease progression in AD patients . SIGNIFICANCE The P300 latency may reflect cognitive decline more sensitively than neuropsychological tests in the longitudinal follow-up of AD patients OBJECTIVE Previous studies indicate that people respond defensively to threatening health information , especially when the information challenges self-relevant goals . The authors investigated whether reduced acceptance of self-relevant health risk information is already visible in early attention processes , that is , attention disengagement processes . DESIGN In a r and omized , controlled trial with 29 smoking and nonsmoking students , a variant of Posner 's cueing task was used in combination with the high-temporal resolution method of event-related brain potentials ( ERPs ) . MAIN OUTCOME MEASURES Reaction times and P300 ERP . RESULTS Smokers showed lower P300 amplitudes in response to high- as opposed to low-threat invalid trials when moving their attention to a target in the opposite visual field , indicating more efficient attention disengagement processes . Furthermore , both smokers and nonsmokers showed increased P300 amplitudes in response to the presentation of high- as opposed to low-threat valid trials , indicating threat-induced attention-capturing processes . Reaction time measures did not support the ERP data , indicating that the ERP measure can be extremely informative to measure low-level attention biases in health communication . CONCLUSION The findings provide the first neuroscientific support for the hypothesis that threatening health information causes more efficient disengagement among those for whom the health threat is self-relevant Event-related potentials ( ERPs ) can eluci date aspects of sensory and cognitive processing that have been compromised due to closed head injury . We present the results of two investigations , one previously unreported , in which we used ERPs to evaluate information processing in head-injury survivors . In the first study , we used visual and auditory reaction time tasks differing in attentional dem and s to assess processing after head trauma . We found numerous changes in auditory processing in survivors : longer reaction times ( but normal accuracy ) , longer N200 and P300 latencies , and reduced N100 and N200 amplitudes . In contrast , on visual tasks , only reduced N200 amplitude distinguished survivors and controls . To increase attentional dem and s , in a second study , we administered the continuous performance test ( CPT ) . Survivors performed with lower accuracy than controls on visual and auditory tasks , and their ERPs were characterized by smaller visual and auditory N200s and P300s and smaller auditory N100s . We also present a synthesis , derived from a review of the literature , of closed head-injury effects on ERPs . Our own findings are in agreement with that synthesis . Namely , cognitive ERP components are more sensitive than sensory components to the effects of trauma . Specifically , in survivors , the amplitudes of N200 and P300 are often reduced , and their latencies prolonged . In general , as compared with visual ERPs , auditory ERPs may be more susceptible to the effects of closed head injury , suggesting that the auditory processing system is more vulnerable than the visual system . We conclude by discussing the potential use of ERPs to monitor clinical course and recovery in survivors of closed head injury The aim of this study was to eluci date the chronic effects of tobacco smoking on the P300 , a neurophysiological index of cognitive function . Prospect i ve study participants were recruited from a family medicine polyclinic . We selected 32 right-h and ed smokers who had smoked more than 15 cigarettes per day , by inhalation , for more than 2 years . The control population consisted of 32 right-h and ed , age-matched healthy individuals who had never smoked . Event-related potentials ( ERPs ) were recorded with the auditory " oddball " two-tone discrimination task . The data from the central ( Cz ) and frontal ( Fz ) electrodes were analyzed . The P300 and N1 amplitudes at Fz were lower in the study population compared to the control group . The early component of ERP , the measure of mental speed ( N1 ) latency at Fz was prolonged in the study group compared to the controls , possibly because early cognitive processes such as sensory input or initial encoding of sensory information were delayed in this group . For those who smoke , a decreased N1 amplitude might indicate delayed information processing and possibly short-term memory disturbance . Thus , chronic tobacco smoking may produce prefrontal cognitive dysfunction BACKGROUND P300 event-related brain potential ( ERP ) amplitude is reduced in patients with schizophrenia . Little attention has been paid to gender differences underlying this abnormality , despite clinical differences between male and female schizophrenics . Studies have also largely ignored the fact that the P300 represents the activity of multiple neural generators and have not assessed the separate activity of different subcomponents . METHODS Auditory P300 ERPs were recorded from 65 patients ( 42 male , 23 female ) and 48 controls ( 30 male , 18 female ) . Positive and negative symptoms were assessed with st and ardized rating scales , and patients were subtyped as deficit or nondeficit . Five P300 subcomponents were identified using current source density measures : frontal ( P3f ) , bilateral parietal ( P3pL , P3pR ) , and bilateral temporal ( P3tL , P3tR ) . RESULTS Three subcomponents ( P3tL , P3f , P3pR ) were reduced in patients . The left temporal ( P3tL ) deficit was common across patient groups , but the overall profile of P300 abnormalities varied by gender and deficit/nondeficit status . Women had greater P3tL and P3f decrements ; P3pR was abnormal in men . Deficit and nondeficit patients resembled men and women , respectively , independent of gender . P3f and P3tL amplitudes were correlated and unrelated to symptomatology . P3pR was related to Brief Psychiatric Rating Scale score . CONCLUSIONS A left temporal abnormality exists in schizophrenia , along with two different profiles of regional pathology , which segregate by gender and deficit/nondeficit status . This supports the hypothesis of two distinct illness subtypes and suggests a physiological basis for phenotypic gender and deficit/nondeficit differences . P300 subcomponent abnormalities may serve as subtype markers . Correlated left temporal and frontal dysfunction is consistent with a frontotemporal neural network disturbance in some schizophrenics . Further investigation of the longitudinal stability and familial inheritance of these subcomponent abnormalities is warranted A better underst and ing of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem . The P300 event-related potential ( ERP ) has emerged as a valuable (endo)phenotype in neuropsychiatric research . Previous studies suggested the P300 ERP to be reduced in smokers . The main purpose of the present study was to provide an in-depth description of smoking-related behavioral , biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters . In this case-control study N=1318 participants ( smokers and never-smoking controls ) were investigated at 6 German academic institutions . Study participants were r and omly selected from the general population . Subjects with mental disorders including alcoholism and drug abuse were excluded . The main outcome measure was the P300 global field power ( GFP ) . We found a lower P300 GFP in current smokers compared to never-smoking controls . Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found . Non-addicted smokers exhibited normal P300 ERP measures . This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity . Thus , P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers . Our results provide the phenotypical groundwork for future multidimensional analyses of genotype-phenotype relationships in the field of smoking and nicotine dependence |
11,268 | 18,416,792 | Concerning the healing of the pressure ulcer , hydrocolloids are more effective than gauze dressings for the reduction of the wound dimensions .
The absorption capacity , the time needed for dressing changes , the pain during dressing changes and the side-effects were significantly in favour of hydrocolloids if compared to gauze dressings .
Based on the available cost-effectiveness data , hydrocolloids seemed to be less expensive compared with collagen- , saline- and povidine-soaked gauze but more expensive compared to hydrogel , polyurethane foam and collagenase .
CONCLUSIONS This review demonstrates that hydrocolloids are to be preferred to gauze dressings in the treatment of pressure ulcers .
RELEVANCE TO CLINICAL PRACTICE Based on the studies included in this review , hydrocolloids are frequently used in the treatment of grade 2 and 3 pressure ulcers and are more effective and less expensive than gauze dressings .
Compared with alginates , polyurethane dressings , less-contact layers , topical enzymes and biosynthetic dressings , hydrocolloids are less effective | AIMS AND OBJECTIVES The aim of this systematic literature review was to describe the current evidence in the field of pressure ulcer treatment with hydrocolloids and to give recommendations for clinical practice and further research .
BACKGROUND Pressure ulcers are a common problem in clinical practice and generate substantial expense .
A wide range of dressings is available but little is known about the effect on pressure ulcer healing . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Background Pressure sores are important and common complications of spinal cord injury . Many preventive and therapeutic approaches have been tried and new trials are evolving . One relatively recent method is application of a hydrocolloid dressing ( HD ) . In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications , phenytoin cream ( PC ) and simple dressing ( SD ) . Methods Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were r and omly allocated to three treatment groups . Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg , respectively . All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses , and the ulcer status was recorded as " Complete healing " , " Partial healing " , " Without improvement " and " Worsening " . Results Complete healing of ulcers , regardless of location and stage , was better in the HD group than the PC [ 23/31(74.19 % ) vs 12/30(40 % ) ; difference : 34.19 % , 95 % CI = 10.85–57.52 , ( P < 0.01 ) ] or the SD [ 23/31(74.19 % ) vs 8/30(26.66 % ) ; difference : 47.53 % , 95 % CI = 25.45–69.61 , ( P < 0.005 ) ] groups . Complete healing of stage I ulcers in the HD group [ 11/13(85 % ) ] was better than in the SD [ 5/11(45 % ) ; difference : 40 % , 95 % CI = 4.7–75.22 , ( P < 0.05 ) ] or PC [ 2/9 ( 22 % ) ; difference : 63 % , 95 % CI = 29.69–96.3 , ( P < 0.005 ) ] groups . Complete healing of stage II ulcer in the HD group [ 12/18 ( 67 % ) ] was better than in the SD group [ 3/19(16 % ) ; difference : 51 % , 95 % CI = 23.73–78.26 , ( P < 0.005 ) ] , but not significantly different from the PC group [ 10/21 ( 48 % ) ; difference : 19 % , 95 % CI = -11.47–49.47 , ( P > 0.05 ) ] . We performed a second analysis considering only one ulcer per patient ( i.e. 83 ulcers in 83 patients ) . This " per patient " analysis showed that complete ulcer healing in the HD group was better than in the PC [ 20/28(71.4 % ) vs 11/28 ( 39.3 % ) ; difference : 32.1 % , 95 % CI = 7.4–56.7 , ( P < 0.01 ) ] or SD [ 20/28(71.4 % ) vs 8/27 ( 29.6 % ) ; difference : 41.8 % , 95 % CI = 17.7–65.8 , ( P < 0.005 ) ] groups . Conclusion We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men An occlusive hydrocolloid dressing ( Comfeel Ulcus ) was compared with a conventional wet saline gauze dressing regarding the effect on ulcer cleansing and healing processes , experience of pain and the consumption of nursing time , in a controlled , r and omized and partially single-blind study with parallel groups of long-stay patients with pressure sores . After a few weeks ' treatment the relative decrease in ulcer areas with time was larger in the group treated with the hydrocolloid dressing . The difference was almost statistically significant at week 5 ( p = 0.054 ) and definite at week 6 ( p = 0.006 ) . At week 6 the median remaining ulcer area in per cent of the initial area was 0 % in the hydrocolloid dressing group and 31 % in the group treated with saline gauze ( p = 0.016 ) . Analysis of the healing distribution function showed the hydrocolloid dressing to be more effective , although the overall difference was non-significant ( p = 0.15 ) . Care of the pressure sore took significantly less time with hydrocolloid dressings Nonprofessional caregivers currently are participating in managing pressure ulcers at home . As this can be a stressful experience , innovative and easy-to-use products are needed to support caregiver confidence . A multicenter , r and omized clinical trial was conducted to compare clinical performance and case of instruction of a change indicator dressing ( SIG ) and a hydrocolloid alginate dressing ( HAD ) in the management of pressure ulcers in the home and long-term care setting s. SIG and HAD were r and omized to 17 and 18 partial- or full-thickness pressure ulcers respectively . During five dressing changes , wound area , dressing application , maintenance , appearance , removal , wear time , ease of teaching , and caregiver underst and ing of each dressing 's instructions were measured . Both dressings were rated highly regarding ease of teaching , ease of use , appearance , maintenance , and helpfulness in signaling the need for dressing change by both professional and nonprofessional wound caregivers . Average dressing wear time was 3.2 days for SIG and 2.7 days for HAD . Of these wounds managed in a moist environment , 6 of 17 ( 35 % ) subjects whose wounds were dressed with SIG , and 1 of 18 ( 6 % ) dressed with HAD healed during the course of the study ( alpha < 0.04 ) . Percent wound reduction in area per day of care was also greater for SIG ( alpha < 0.01 ) . Innovative dressings may help caregivers provide consistent quality pressure ulcer care and improve wound-healing outcomes A hydropolymer dressing ( Tielle ) and a hydrocolloid dressing ( Granuflex ) were compared in a r and omised controlled clinical study involving 100 patients with leg ulcers and 99 patients with pressure sores in the community . Statistically significant differences in favour of the hydropolymer dressing were detected for dressing leakage and odour production , but no statistically significant differences were recorded in the number of patients with either leg ulcers or pressure sores who healed in each treatment group The management of pressure sores in community setting s , poses a clinical problem which challenges the patient ’s tolerance and the clinician ’s diligence and ingenuity . Pressure sores can be painful , lead to infection and are associated with considerable morbidity and increased mortality ( Patterson & Bennett , 1995:919 ; Bale , Banks , Hagelstein & Harding , 1998:65 ) . Treatment costs of these wounds are high in terms of re sources ( Colin 1995:65 ; Wood , Griffiths & Stoner , 1997:256 ) . However , since there are untold cost in terms of pain and suffering to the patient , it is impossible to calculate the true cost of pressure sores ( Dealey , 1994:87 ) OBJECTIVES To compare the effects of topical collagen and hydrocolloid on pressure ulcer healing . DESIGN R and omized ( allocation concealed ) , single-blind ( outcome assessors ) , controlled trial with 8-week follow-up . SETTING Eleven nursing homes in central Illinois . PARTICIPANTS Sixty-five patient-residents with Stage II or III pressure ulcers : median age 83.1 , median Braden score 12 , 63 % female , 80 % Stage II ulcers , and 20 % Stage III ulcers . Exclusion criteria included cellulitis and osteomyelitis . INTERVENTION Thirty-five patients were allocated to topical collagen daily , 30 to topical hydrocolloid twice weekly . MEASUREMENTS The primary outcome was complete healing within 8 weeks . Secondary outcomes were time to heal , ulcer area healed per day , linear healing of wound edge , and cost of therapy . RESULTS Analysis by intention to treat revealed similar complete ulcer healing within 8 weeks in collagen ( 51 % ) and hydrocolloid ( 50 % ) recipients ( difference 1 % , 95 % confidence interval ( CI ) = 26 - 29 % ) . Mean healing time was similar : collagen healed in 5 weeks ( 95 % CI = 4 - 6 ) , hydrocolloid healed in 6 weeks ( 95 % CI = 5 - 7 ) . Mean area healed per day was 6 mm(2)/d in both treatment groups . Mean linear healing of the wound edge was 3 mm in both groups . In multivariate analysis , baseline ulcer depth was the only independent predictor of complete ulcer healing within 8 weeks ( odds ratio = 0.56 , 95 % CI = 0.38 - 0.81 ) . Cost analysis favored hydrocolloid . CONCLUSIONS There were no significant differences in healing outcome between collagen and hydrocolloid . Collagen was more expensive and offered no major benefits to patients otherwise eligible for hydrocolloid treatment A total of 67 patients with pressure ulcers were r and omized into one of three treatment modalities : hydrogel sheet dressing , hydrocolloid , or wet-to-moist gauze . Safety , efficacy , and physical attributes of the three dressings were evaluated . No statistical significance was found in wound healing rate among the three treatments . Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption One-hundred and three patients with Stage II and III sacral pressure ulcers were enrolled in a prospect i ve , controlled , multi-center clinical study to evaluate and compare dressing performance , safety and efficacy . Fifty-two patients were r and omized to treatment with a triangle-shaped hydrocolloid border dressing and 51 patients were r and omized to a different , oval shape , hydrocolloid dressing . The majority of patients ( 70 percent ) utilized a pressure reducing mattress or bed . Most ulcers were Stage II , had existed for < 1 month and exhibited no change utilizing previous treatments . Patients and wounds were similarly distributed among treatment groups . Patients in the oval dressing group were more likely to exhibit a product related adverse reaction result ing in discontinuation of treatment as compared to patients treated with the triangle border dressing ( p = 0.057 , Fisher 's Exact Test ) . Wear time was longest for wounds dressed with the triangle dressing applied point down . Incontinence reduced the interval between dressing changes in both groups . Healing was more likely to occur in wounds dressed with the triangle border dressing . These ulcers showed a greater reduction in ulcer width as compared to wounds dressed with the oval dressing ( p < 0.03 , Fisher 's Exact Test ) This study compared an adhesive hydrocellular dressing with a leading hydrocolloid dressing in the management of pressure ulcers . Forty adult patients of both sexes who had Stage II or III pressure ulcers ( according to the Agency for Health Care Policy and Research system ) were enrolled in the study and were r and omized to either the hydrocellular or hydrocolloid dressing . Dressing changes were done as required , and each ulcer was assessed on a weekly basis . Patients were followed for 8 weeks , until ulcer closure was achieved , or until the patient was withdrawn from the study , whichever occurred first . The hydrocellular dressing was found to compare favorably with the hydrocolloid dressing . In terms of ease of use , the hydrocellular dressing was found to be significantly easier to remove ( P < 0.001 ) and quicker to change ( P < 0.001 ) than the hydrocolloid dressing . No differences were detected between the two dressing groups regarding mean wound pain , odor , and changes in ulcer appearance and ulcer area OBJECTIVES Pressure ulcers , like other chronic wounds , fail to proceed through an orderly and timely process to produce anatomical or functional integrity . Treatment of pressure ulcers is directed to improving host factors and providing an optimum wound environment . In addition to providing a moist wound environment , it has been theorized that preventing hypothermia in a wound and maintaining a normothermic state might improve wound healing . DESIGN / SETTING Forty-one subjects with a stage 3 or stage 4 truncal pressure ulcer > 1.0 cm(2 ) were recruited from outpatient clinics , long-term care nursing homes , and a rehabilitation center . The experimental group was r and omized to a radiant-heat dressing device and the control group was r and omized to a hydrocolloid dressing , with or without a calcium alginate filler . Subjects were followed until healed or for 12 weeks . RESULTS Eight subjects ( 57 % ) in the experimental group had complete healing of their pressure ulcer compared with 7 subjects ( 44 % ) with complete healing in the control group ( P = .46 ) . CONCLUSION Although a 13 % difference in healing rate between the two arms of the study was found , this difference was not statistically significant . At almost all points along the healing curve , the proportion not healed was higher in the control arm OBJECTIVE To determine the effect of noncontact normothermic wound therapy ( NNWT ) versus st and ard wound care on chronic full-thickness pressure ulcers . DESIGN Prospect i ve , r and omized , controlled trial SETTING Veterans administration medical center and 7 long-term-care facilities PATIENTS 40 in patients with 43 Stage III and IV pressure ulcers INTERVENTIONS A sterile noncontact wound dressing was applied to 21 wounds for 24 hours per day , 7 days per week . Each day after the wound was irrigated and the noncontact dressing was changed , a heating element in the dressing was activated for 3 1-hour periods for 12 weeks or until wound closure . Twenty-two control wounds were treated with st and ard , moisture-retentive dressings 24 hours per day , 7 days per week for 12 weeks or until wound closure . MAIN OUTCOME MEASURE Measurement of wound surface area MAIN RESULTS Healing rate for the NNWT group was significantly greater than for the control group ( 0.52 cm2 per week and 0.23 cm2 per week , respectively;P < .02 ) . A clinical ly significant increase was seen among the NNWT group in the incidence of closure among wounds that completed the entire 12-week protocol compared with controls ( 11 of 14 or 79 % and 8 of 16 or 50 % , respectively ; not significant ) . The mean slope of the individual regression analyses for the NNWT group was significantly different from the mean slope for the control group ( −0.07 and −0.033 , respectively;P < .05 ) . Large wounds in the NNWT group demonstrated a significantly greater healing rate than large wounds in the control group ( P < .05 ) . CONCLUSION Wounds treated with NNWT healed significantly faster than wounds in the control group . The healing rate was greatest for larger wounds treated with NNWT OBJECTIVE To compare the clinical effectiveness and wound management properties of a copolymer membrane , Inerpan ( Synthélabo ) , and a hydrocolloid dressing , Comfeel ( Coloplast ) , in the treatment of decubitus ulcers in the elderly . DESIGN Open , r and omized , multicentric French study , with two parallel groups of patients . PATIENTS 168 in- patients aged more 65 years ( mean age : 82 years ) suffering from grade II to grade IV ( in the Shea classification ) pressure sores . TRIAL PERIOD : Either 8 weeks or until the ulcer healed , whichever occurred first . MEASUREMENTS In addition to a complete physical examination , patients were evaluated at baseline for nutritional status and risk factors . The wounds were described , their depth scored , and the areas traced at Weeks 0 , 1 , 2 , 4 , 6 , and 8 . The number of dressings used was recorded . RESULTS Thirty-one Inerpan-treated patients and 23 Comfeel-treated patients achieved healing ( P = 0.089 ) , with respective median healing times of 32 and 38 days . Healing times were compared using survival curves ( in the whole population ) adjusted for ulcer depth effect and showed a significant difference in favor of Inerpan ( P = 0.044 and 0.014 ) . Progress of healing ( percentage of ulcer healed ) was calculated in the two groups . Clinical ly assessed the treatment performance scored at the completion of the study showed better results with Inerpan ( P < 0.05 ) . Both groups were similar in terms of granulation/exudation scores , surrounding skin , and ease of care . CONCLUSION It is concluded that Inerpan is easy to use , safeguards the healing process , and is of particular value in the management of pressure sores OBJECTIVE To conduct a cost-of-illness study of pressure ulcers in the Netherl and s for different care setting s , including home care , nursing homes , general hospitals , and university hospitals . DESIGN A cost-of-illness study was conducted based on prevalence figures and expert opinion . A differential cost study approach was used , distinguishing among the 4 stages of pressure ulcer severity and the different care setting s. To obtain expert opinion , structured interviews were conducted with pressure ulcer experts who were chosen r and omly from the membership of the Dutch Society of Pressure Ulcer Experts . Information was gathered on volume of care parameters for each pressure ulcer stage , including personnel , extra days of care , and use of special beds and medical material s. Experts were asked to estimate the percentage of patients for which each care parameter was considered relevant ; low and high estimates of each figure were given to determine the range of the calculations . Cost estimates were obtained from Dutch guidelines for cost calculations in health care , then converted to US dollars . SETTING Home care , nursing homes , general hospitals , and university hospitals in the Netherl and s. PARTICIPANTS Experts on pressure ulcer management working in the different care setting s. MAIN OUTCOME MEASURE Cost-of-illness of pressure ulcers , converted to US dollars . MAIN RESULTS The cost-of-illness of pressure ulcers ranged from a low estimate of $ 362 million to a high estimate of $ 2.8 billion . The most conservative estimate is approximately 1 % of the total Dutch health care budget . CONCLUSION The cost-of-illness of pressure ulcers in the Netherl and s is considerable Abstract Objective : To evaluate the efficacy and cost effectiveness of two treatments of pressure sores on the heel : a collagenase-containing ointment and a hydrocolloid dressing . Design : Study and cost data were collected prospect ively in a r and omised clinical trial in The Netherl and s by counting the re source use for each patient until wound healing occurred . Study participants : All 24 female study participants were in patients from the same hospital with grade IV pressure sores on the heel following orthopaedic surgery . Interventions : Two different treatment strategies were analysed : a collagenase-containing ointment ( Novuxol ® ) and a hydrocolloid dressing (Duoderm ® ).1Perspective : Hospital perspective . Main outcome measures and results : The average costs per patient for treatment with the hydrocolloid dressing were about 5 % higher than those with the collagenase-containing ointment . The treatment costs were similarly distributed within both groups , with 34 % for material s and 66 % for personnel . The cost-effectiveness analysis revealed that cost savings of 899 Dutch guilders ( 1998 values ) per successfully treated patient could be expected using the collagenase-containing ointment instead of the hydrocolloid dressing . In addition , wound healing was achieved , on average , within a shorter time period with the collagenase treatment ( 10 weeks ) compared with the hydrocolloid treatment ( 14 weeks ) . The robustness of the results were also tested using sensitivity analyses . These analyses served to confirm that collagenase treatment provides a better cost-effectiveness ratio than hydrocolloid treatment . Conclusions : With regard to overall costs and costs per successfully treated patient , this study showed collagenase treatment to be more cost effective than the hydrocolloid treatment in patients with grade IV pressure sores on the heel and that the amount of time needed for wound healing was shorter Stage II and III pressure ulcers present product development and product choice challenges to manufacturers and professional wound care clinicians respectively . We evaluated the clinical performance and cost of use associated with a new synthetic polymer dressing for the management of these wounds . A total of 10 home healthcare patients , each with a Stage II or III pressure ulcer , were enrolled and r and omized for wound treatment using either the new polymer hydrogel wound dressing or the leading market hydrocolloid dressing . Dressings were changed on an as needed basis only . The wounds were assessed weekly and parameters recorded using the Bates-Jensen Pressure Sore Status Tool . In addition , the clinical performance of the dressing and treatment costs were evaluated . The overall healing rate for the two groups was similar . However the new polymer hydrogel dressing was found to have a more favorable overall clinical performance evaluation based largely on its more favorable support of autolytic debridement . The new polymeric dressing also had a more favorable cost of use based on the evaluation . We conclude that the new polymer dressing may be a favorable alternative to the leading market hydrocolloid dressing for the treatment of Stage II and III pressure ulcers due to a better clinical performance and the substantially lower treatment costs associated with its use The efficacy of hydrocolloid occlusive dressing technique was compared with that of the conventional wet-to-dry gauze dressing technique in decubitus ulcer of stage I and II . Forty-four patients were r and omly divided into two treatment groups and each received treatment according to the two different protocol s. As a result , 80.8 % of the hydrocolloid occlusive dressing group ( group 1 ) and 77.8 % of the conventional wet-to-dry gauze dressing group ( group 2 ) healed completely with no statistically significant difference between the two groups . However , the time required for complete healing was shorter in group 1 with 18.9 days compared to 24.3 days in group 2 . Ulcer healing speed was also slightly faster in group 1 with 9.1 mm2/day compared to 7.9 mm2/day for group 2 . Average treatment time spent by a medical staff member was significantly shorter in group 1 with 20.4 minutes/day compared to 2017 minutes/day in group 2 . The hospital cost of the ulcer treatment was higher in group 2 compared to group 1 even without taking into consideration the medical personnel 's labor cost . These results indicate that the hydrocolloid occlusive dressing technique offers less time consuming and less expensive method of treatment compared to the conventional technique in stage I and II decubitus ulcers Objective This study compared healing rates in stage III and IV pressure ulcers treated with noncontact normothermic wound therapy or moist dressings . Periwound temperature changes with noncontact normothermic wound therapy were evaluated . Design This 8-week , prospect i ve , r and omized clinical trial evaluated linear rate of healing of the wound edge and periwound temperature changes during the 1-hour warming treatment and for 15 minutes after warming . Setting and subjects Forty subjects referred from primary care providers , home care providers , acute care facilities , and long-term care facilities were enrolled in the study . Twenty-nine subjects completed the trial ( 14 received st and ard care , and 15 received noncontact normothermic wound therapy ) . Instruments Ulcers were measured with acetate tracings , digital and Polaroid photography , and Pressure Sore Status Tool evaluations . The linear rate of healing was determined with use of computerized planimetry . Periwound temperatures were recorded with use of a Cole Parmer thermometer YSI 400 series . Methods Subjects were evaluated weekly . Subjects r and omly assigned to noncontact normothermic wound therapy received 3 treatments daily , during which the dressing was warmed to 38 ° C for 1 hour . Subjects in the st and ard care group were treated with dressings that were moisture retentive and provided absorption as needed . Results The two groups were statistically similar with regard to baseline and wound characteristics . The linear rate of healing was significantly faster in the group treated with noncontact normothermic wound therapy ( Mann-Whitney U test = 47 , P = .01 ) . On average , periwound temperatures increased 2.4 ° C at the end of warming ( 1 hour ) , a significant increase above baseline values ( P = .001 ) . Conclusions The healing rate was significantly increased with noncontact normothermic wound therapy treatment . Periwound temperature increased significantly after 1 hour of warming , achieving levels approximating normothermia . Healing effects associated with noncontact normothermic wound therapy may be related to several mechanisms , including improvements in perfusion , oxygen supply , and cellular activity in response to warming This study compares the costs of dressings used in the treatment of patients with a variety of wound aetiologies . The two dressings investigated were a hydrocolloid dressing and a hydrocellular dressing . Secondary objectives included a comparison of dressing durability , time to complete healing , ease of wound cleansing and dressing removal . The study was an open prospect i ve single-centre r and omised parallel group trial involving 100 patients , treated in the community , who were r and omised to the two dressing groups . For all aetiologies except pressure sores , the costs of the hydrocolloid dressing were less than the costs of the hydrocellular dressings . Similar healing rates were observed in the leg ulcer and ' other wound ' groups . There were , however , significant differences in the number of healed wounds observed in patients with pressure sores treated with the hydrocellular dressing THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard To compare the efficacy and the cost-effectiveness of moist gauze dressings and a hydrocolloid wafer dressing ( DuoDERM CGF ) , 70 patients with 97 pressure ulcers that were stage II and /or stage III were r and omly assigned to one of two treatment methods : moist gauze dressings or hydrocolloid dressings . Efficacy was defined as the number of ulcers that completely healed . In this debilitated , poorly nourished group of patients , one ulcer completely healed in the moist gauze dressing group , and 11 healed in the hydrocolloid group . The per diem cost of the moist gauze dressing was $ 12.26 ; the per diem cost of the hydrocolloid dressing was $ 3.55 BACKGROUND studies of the effectiveness of alternating pressure air mattresses ( APAMs ) for the prevention of pressure ulcers are scarce and in conflict . OBJECTIVE evaluating whether an APAM is more or equally effective as the st and ard prevention . DESIGN r and omised controlled trial . SETTING AND SUBJECTS patients admitted to 19 surgical , internal , or geriatric wards in seven Belgian hospitals were included if they were in need of prevention of pressure ulcers . To define this need , two methods were used r and omly : the Braden Scale or the presence of non-blanchable erythema ( NBE ) . METHODS 447 patients were r and omised into either an experimental or a control group . In the experimental group , 222 patients were lying on an APAM ( Alpha-X-Cell , Huntleigh Healthcare , UK ) . In the control group , 225 patients were lying on a visco-elastic foam mattress ( Tempur , Tempur-World Inc. , USA ) in combination with turning every 4 hours . Both groups had identical sitting protocol s. RESULTS there was no significant difference in incidence of pressure ulcers ( grade 2 - 4 ) between the experimental ( 15.6 % ) and control group ( 15.3 % ) ( P = 1 ) . There were significantly more heel pressure ulcers in the control group ( P = 0.006 ) . There was an interaction effect between the risk assessment method and preventive measures for the development of all pressure ulcers and sacral pressure ulcers . CONCLUSION fewer patients developed heel pressure ulcers on an APAM . Patients identified as being in need of prevention based on the presence of NBE had a tendency to develop fewer pressure ulcers on an APAM . Patients identified as being in need of prevention , based on the Braden Scale , appeared to develop more sacral pressure ulcers on an APAM This study compared a polyurethane foam dressing with a hydrocolloid dressing for ease of application and removal , adhesion , conformability , absorbency and wear time . A r and omised study was carried out , including 61 patients with stage two or three pressure sores in five centres in the UK . Dressings were applied for up to 30 days and assessment s were carried out at each dressing change . The results indicated that both dressings are easy and convenient to apply ; absorbency and ease of removal were significantly better with the polyurethane foam dressing than the hydrocolloid dressing ; wear times were similar BACKGROUND Turning is considered to be an effective way of preventing pressure ulcers , however almost no research has been undertaken on this method . AIM The aim of the study was to investigate the effect of four different preventative regimes involving either frequent turning ( 2 , 3 hourly ) or the use of a pressure-reducing mattress in combination with less frequent turning ( 4 , 6 hourly ) . SUBJECTS 838 geriatric nursing home patients participated in the study . METHODS During 28 days , four different turning schemes were used : turning every 2 h on a st and ard institutional ( SI ) mattress ( n = 65 ) , turning every 3 h on a SI mattress ( n = 65 ) , turning every 4 h on a viscoelastic foam ( VE ) mattress ( n = 67 ) , and turning every 6h on a VE mattress ( n = 65 ) . The remaining patients ( n = 576 ) received st and ard preventive care . MAIN RESULTS The incidence of non-blanchable erythema ( 34.8 - 38.1 % ) was not different between the groups . The incidence of grade II and higher pressure ulcers in the 4h interval group was 3.0 % , compared with incidence figures in the other groups varying between 14.3 % and 24.1 % . CONCLUSIONS Turning every 4 h on a VE mattress result ed in a significant reduction in the number of pressure ulcer lesions and makes turning a feasible preventive method in terms of effort and cost OBJECTIVES To compare the efficacy of a sequential strategy combining calcium alginate and hydrocolloid dressings treatment of grade III or IV pressure ulcers ( PUs ) and the efficacy of nonsequential strategy with hydrocolloids alone . DESIGN An open , r and omized , multicenter parallel-group trial . SETTING Twenty geriatrics hospital wards . PARTICIPANTS One hundred ten older patients with grade III or IV PUs . INTERVENTION The control strategy consisted of applying hydrocolloid dressings ( DuodermE ) for 8 weeks ; the sequential strategy consisted of applying combined calcium alginate dressings ( UrgoSorb ) for the first 4 weeks and hydrocolloid dressings ( Algoplaque ) for the next 4 weeks . MEASUREMENTS PU surface areas were measured weekly by ulcer tracing . The endpoints were the mean absolute surface area reduction ( SAR ) during the 8-week study period and the number of patients achieving a 40 or more SAR ( SAR40 ) . RESULTS Fifty-seven and 53 patients were r and omly allocated to sequential and control strategies respectively . Baseline patient characteristics and PU ulcer features at inclusion were similar in the two groups . Mean + /- st and ard deviation SAR was significantly larger in the sequential treatment group ( 5.4 + /- 5.7 cm2 and 7.6 + /- 7.1 cm2 at 4 and 8 weeks ) than in the control group ( 1.6 + /- 4.9 cm2 and 3.1 + /- 7.2 cm2 , P < .001 ) . In the sequential treatment group , 68.4 of the patients reached SAR40 at 4 weeks and 75.4 at 8 weeks , proportions significantly larger than in the control group ( 22.6 and 58.5 , respectively , P < .0001 ) . Dressing tolerance was good in both strategies . CONCLUSIONS In grade III or IV PUs , treatment using first calcium alginate dressings and then hydrocolloid dressings promotes faster healing than treatment with hydrocolloid dressings alone An open comparative r and omised study comparing the performance of hydrocolloid dressings ( DuoDERM CGF ) to saline gauze dressings in the treatment of pressure ulcers was done to evaluate the overall dressing performance , wound healing and cost effectiveness . Thirty-four subjects were enrolled at the University Hospital , Kuala Lumpur over a 643 days period . Inclusion criteria were Stage II or III pressure ulcers , at least 18 years of age and written informed consent . Only one pressure ulcer per subject was enrolled in the study . Patients with infected pressure ulcers , diabetes mellitus , an immuno-compromised status and known sensitivity to the study dressings were excluded . Subjects who met the enrollment criteria were r and omised to one of the two dressing regimes . They were expected to participate in the study for a maximum of eight weeks or until the pressure ulcer healed , which ever occurred first . Overall subject age averaged 58 years and the mean duration of pressure ulcer existence was about 1 month . Twenty-one of the thirty-four ulcers enrolled were stage II and thirteen were stage III . The majority of the ulcers ( 88 % ) were located in the sacral area and seventeen subjects ( 50 % ) were incontinent . In the evaluation of dressing performance in terms of adherence to wound bed , exu date h and ling ability , overall comfort and pain during dressing removal ; all favoured the hydrocolloid dressing by a statistically significant margin ( p < 0.001 ) . Subjects assigned the hydrocolloid dressing experienced a mean 34 % reduction from their baseline surface area measurement compared to a mean 9 % increase by subjects assigned gauze dressings . This was not statistically significant ( p = 0.2318 ) . In cost evaluation of the study products , there was no statistical significance in the total cost of wound management per subject . When only labour time and cost was evaluated , there was a statistically significant advantage towards hydrocolloid dressings The cost effectiveness of using hydrocolloid dressings versus nonsterile saline-gauze wet-to-moist dressings for treatment of pressure ulcers in a long-term care setting was evaluated . During 21 months , 39 subjects were enrolled , and treatment was r and omly assigned . Eighty-nine percent of the hydrocolloid subjects and 86 % of the saline-gauze subjects healed . Median healing time was shorter for the hydrocolloid group ( nine days ) than for the saline-gauze group ( 11 days ) , although the difference did not reach statistical significance ( p = .12 ) . Presence of exu date at baseline was associated with a prolonged time to healing . For the hydrocolloid treatment , the median nursing time was one eighth that of the saline-gauze treatment , but its material s cost was 3.3 times higher . Using local nursing wages , median total cost for treatment with hydrocolloid dressing was $ 15.58 ; for the saline gauze , it was $ 22.65 . Using national nursing wages , these costs were $ 15.90 and $ 25.31 , respectively . The cost savings of the hydrocolloid treatment using local wages did not reach statistical significance . However , using national wages , the cost of the hydrocolloid treatment was significantly less expensive . Nursing home treatment of pressure ulcers was inexpensive overall . Consequently , the absolute cost savings of using hydrocolloid dressings instead of nonsterile saline-gauze dressing , although real , was relatively modest . Physicians can use local nursing wages to calculate the magnitude of savings in their area |
11,269 | 28,813,109 | In 90 % of the studies review ed the presence of inhibitory control deficits was reported , verified by impaired cognitive processing and response monitoring , as well as high levels of impulsiveness , regardless of the pattern of crack and /or cocaine consumption ( recreational or chronic ) .
Former users showed high levels of impulsiveness even after long periods of abstinence .
Crack and /or cocaine users may have inhibitory control deficits , irrespective of different consumption patterns .
High levels of impulsiveness can represent a factor of vulnerability to drug use and relapse | OBJECTIVE Impairments involving inhibitory control have been considered central deficits in drug users , but it appears that dysfunctions may be specific to users ' drug of choice .
This article aims to review recent findings on inhibitory control impairment in sample s of crack and /or cocaine users . | Abstract The relationship of the degree of use of each of ten types of illicit drugs with each of eight types of violent criminal offenses , is reported for an African-American , inner-city , low SES , young adult study sample ( N = 612 ) . Prospect i ve data from the time of birth was available for the statistical analyses , to provide 51 control variables on factors other than substance use which might predict to later violent behavior . Findings : Greater frequency of use of marijuana was found unexpectedly to be associated with greater likelihood to commit weapons offenses ; and this association was not found for any of the other drugs , except for alcohol . Marijuana use was also found associated with commission of Attempted Homicide/Reckless Endangerment offenses . Cocaine/crack and marijuana were the only two types of drugs the frequency of use of which was found , for this sample , to be significantly related to the frequency of being involved in the selling of drugs . These findings may not apply to a middle-class African-American sample Long-term cocaine and alcohol use is associated with neuropsychological impairments that implicate poor inhibitory mechanisms of behavioural control . This study tested acquisition and discrimination-reversal learning in a group of polydrug users ( n 20 ) with a history of cocaine and heavy alcohol use and a group of age-matched controls ( n 20 ) . A cued go/nogo task measured subjects ’ ability to learn stimulus-response associations that involved the quick activation and sudden inhibition of responses . Compared with controls , drug users displayed similar acquisition , but impaired discrimination-reversal learning of both inhibitory and activational responses . The results suggest that some drug-related neuropsychological deficits might reflect specific impairments of the ability to inhibit interference from prior learning . The findings contribute to growing evidence that suggests cocaine and alcohol use could produce broad inhibitory impairments that increase the risk for learning deficits and poor impulse control Deficits in cognitive control are implicated in cocaine dependence . Previously , combining functional magnetic resonance imaging and a stop signal task , we demonstrated altered cognitive control in cocaine-dependent individuals . However , the clinical implication s of these cross-sectional findings and , in particular , whether the changes were associated with relapse to drug use , were not clear . In a prospect i ve study , we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessment s for 3 months , during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests . Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8 , with the contrast ' stop error greater than stop success trials ' to index error processing . Using voxelwise analysis with logistic and Cox regressions , we identified brain activations of error processing that predict relapse and time to relapse . In females , decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse . In males , decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse . These regional activations were vali date d with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses . These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals . These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating deficits of cognitive control in cocaine addicts Chronic and recreational use of cocaine has been shown to impair inhibitory output control ( response inhibition ) but whether input control is also affected is an open question . For the first time , this study compared the ability to perform a cued target-discrimination task that measured inhibition of return ( IOR ) , a reflexive inhibitory mechanism that delays attention from returning to a previously attended location , in adult recreational users and in a cocaine-free-matched sample controlled for age , race , gender distribution , and level of intelligence . Results show that the recreational use of cocaine eliminates IOR , suggesting that input control is strongly impaired Two experiments investigated attentional biases for smoking-related cues in smokers and nonsmokers , using the visual probe task . In Experiment 1 , when pictures were displayed for 500 ms , smokers who had made repeated quit attempts showed an attentional bias for smoking-related scenes . Experiment 2 replicated this finding and revealed that when pictures were presented for 2,000 ms , the smoker group as a whole showed vigilance for smoking-related cues , but nonsmokers did not . The findings from the 500-ms exposure condition suggest that initial orienting of attention to smoking cues was associated with repeated unsuccessful attempts at abstinence in smokers . Results are discussed with reference to incentive-sensitization theories of addiction and to component processes of selective attention , such as initial orienting versus maintenance |
11,270 | 29,243,221 | Subgroup analyses found no evidence that high-intensity interventions , interventions with additional follow-up or interventions including aids that demonstrate the pathophysiological effect of smoking are more effective than lower intensity interventions , or interventions without additional follow-up or aids .
There was no evidence that the effect of support differed by patient group or across healthcare setting s. AUTHORS ' CONCLUSIONS There is moderate quality evidence that behavioural support to motivate and sustain smoking cessation delivered by nurses can lead to a modest increase in the number of people who achieve prolonged abstinence .
There is insufficient evidence to assess whether more intensive interventions , those incorporating additional follow-up , or those incorporating pathophysiological feedback are more effective than one-off support .
There was no evidence that the effect of support differed by patient group or across healthcare setting | BACKGROUND Healthcare professionals , including nurses , frequently advise people to improve their health by stopping smoking .
Such advice may be brief , or part of more intensive interventions .
OBJECTIVES To determine the effectiveness of nursing-delivered smoking cessation interventions in adults .
To establish whether nursing-delivered smoking cessation interventions are more effective than no intervention ; are more effective if the intervention is more intensive ; differ in effectiveness with health state and setting of the participants ; are more effective if they include follow-ups ; are more effective if they include aids that demonstrate the pathophysiological effect of smoking . | Background There is no more effective intervention for secondary prevention of coronary heart disease than smoking cessation . Yet , evidence about the (cost-)effectiveness of smoking cessation treatment methods for cardiac in patients that also suit nursing practice is scarce . This protocol describes the design of a study on the (cost-)effectiveness of two intensive smoking cessation interventions for hospitalised cardiac patients as well as first results on the inclusion rates and the characteristics of the study population . Methods / design An experimental study design is used in eight cardiac wards of hospitals throughout the Netherl and s to assess the (cost-)effectiveness of two intensive smoking cessation counselling methods both combined with nicotine replacement therapy . R and omization is conducted at the ward level ( cross-over ) . Baseline and follow-up measurements after six and 12 months are obtained . Upon admission to the cardiac ward , nurses assess patients ’ smoking behaviour , ensure a quit advice and subsequently refer patients for either telephone counselling or face-to-face counselling . The counselling interventions have a comparable structure and content but differ in provider and delivery method , and in duration . Both counselling interventions are compared with a control group receiving no additional treatment beyond the usual care . Between December 2009 and June 2011 , 245 cardiac patients who smoked prior to hospitalisation were included in the usual care group , 223 in the telephone counselling group and 157 in the face-to-face counselling group . Patients are predominantly male and have a mean age of 57 years . Acute coronary syndrome is the most frequently reported admission diagnosis . The ultimate goal of the study is to assess the effects of the interventions on smoking abstinence and their cost-effectiveness . Telephone counselling is expected to be more (cost-)effective in highly motivated patients and patients with high SES , whereas face-to-face counselling is expected to be more (cost-)effective in less motivated patients and patients with low SES . Discussion This study examines two intensive smoking cessation interventions for cardiac patients using a multi-centre trial with eight cardiac wards . Although not all eligible patients could be included and the distribution of patients is skewed in the different groups , the results will be able to provide valuable insight into effects and costs of counselling interventions varying in delivery mode and intensity , also concerning subgroups . Trial registration Dutch Trial Register PURPOSE / OBJECTIVES To determine the predictors of participation in a smoking-cessation program among patients with head and neck cancer . DESIGN This cross-sectional study is a sub study of a larger , r and omized trial of patients with head and neck cancer that determined the predictors of smokers ' participation in a cessation intervention . SETTING Otolaryngology clinics at three Veterans Affairs medical centers ( Ann Arbor , MI , Gainesville , FL , and Dallas , TX ) , and the University of Michigan Hospital in Ann Arbor . SAMPLE 286 patients who had smoked within six months of the screening survey were eligible for a smoking-cessation intervention . METHODS Descriptive statistics and bivariate and multivariate logistic regression were used to determine the independent predictors of smokers ' participation in an intervention study . MAIN RESEARCH VARIABLES Perceived difficulty quitting ( as a construct of self-efficacy ) , health behaviors ( i.e. , smoking and problem drinking ) , clinical characteristics ( i.e. , depression and cancer site and stage ) , and demographic variables . FINDINGS Forty-eight percent of those eligible participated . High perceived difficulty quitting was the only statistically significant predictor of participation , whereas problem drinking , lower depressive symptoms , and laryngeal cancer site approached significance . CONCLUSIONS Special outreach may be needed to reach patients with head and neck cancer who are overly confident in quitting , problem drinkers , and patients with laryngeal cancer . IMPLICATION S FOR NURSING Oncology nurses are in an opportune position to assess patients ' perceived difficulty quitting smoking and motivate them to enroll in cessation programs , ultimately improving quality of life , reducing risk of recurrence , and increasing survival for this population Abstract Objective : To evaluate the effects of secondary prevention clinics run by nurses in general practice on the health of patients with coronary heart disease . Design : R and omised controlled trial of clinics over one year with assessment by self completed postal question naires and audit of medical records at the start and end of the trial . Setting : R and om sample of 19 general practice s in northeast Scotl and . Subjects : 1173 patients ( 685 men and 488 women ) under 80 years with working diagnoses of coronary heart disease who did not have terminal illness or dementia and were not housebound . Intervention : Clinic staff promoted medical and lifestyle aspects of secondary prevention and offered regular follow up . Main outcome measures : Health status measured by the SF-36 question naire , chest pain by the angina type specification , and anxiety and depression by the hospital anxiety and depression scale . Use of health services before and during the study . Results : There were significant improvements in six of eight health status domains ( all functioning scales , pain , and general health ) among patients attending the clinic . Role limitations attributed to physical problems improved most ( adjusted difference 8.52 , 95 % confidence interval 4.16 to 12.9 ) . Fewer patients reported worsening chest pain ( odds ratio 0.59 , 95 % confidence interval 0.37 to 0.94 ) . There were no significant effects on anxiety or depression . Fewer intervention group patients required hospital admissions ( 0.64 , 0.48 to 0.86 ) , but general practitioner consultation rates did not alter . Conclusions : Within their first year secondary prevention clinics improved patients ' health and reduced hospital admissions . Key messages Nurse led clinics in general practice were used to promote secondary prevention to patients with coronary heart disease Within the first year the health of patients invited to the clinics improved Most benefit was in functional status , but chest pain improved too There was no effects on anxiety or depression There were significant reductions in hospital admissions in the first Background Intensive lifestyle interventions in well-controlled setting s are effective in lowering the risk of chronic diseases such as type 2 diabetes ( T2DM ) and cardiovascular diseases ( CVD ) , but there are still no effective lifestyle interventions for everyday practice . In the Hoorn Prevention Study we aim ed to assess the effectiveness of a primary care based lifestyle intervention to reduce the estimated risk of developing T2DM and for CVD mortality , and to motivate changes in lifestyle behaviors . Methods The Hoorn Prevention Study is a parallel group r and omized controlled trial , implemented in the region of West-Friesl and , the Netherl and s. 622 adults with ≥10 % estimated risk of T2DM and /or CVD mortality were r and omly assigned and monitored over a period of 12 months . The intervention group ( n=314 ) received a theory-based lifestyle intervention based on an innovative combination of motivational interviewing and problem solving treatment , provided by trained practice nurses in 12 general practice s. The control group ( n=308 ) received existing health brochures . Primary outcomes was the estimated diabetes risk according to the formula of the Atherosclerosis Risk In Communities ( ARIC ) Study , and the estimated risk for CVD mortality according to the Systematic COronary Risk Evaluation ( SCORE ) formula . Secondary outcomes included lifestyle behavior ( diet , physical activity and smoking ) . The research assistants , the principal investigator and the general practitioners were blinded to group assignment . Linear and logistic regression analysis was applied to examine the between-group differences in each outcome measure , adjusted for baseline values . Results 536 ( 86.2 % ) of the 622 participants ( age 43.5 years ) completed the 6-month follow-up , and 502 ( 81.2 % ) completed the 12-month follow-up . The mean baseline T2DM risk was 18.9 % ( SD 8.2 ) and the mean CVD mortality risk was 3.8 % ( SD 3.0 ) . The intervention group participated in a median of 2 sessions . Intention-to-treat analyses showed no significant differences in outcomes between the two groups at 6 or 12-months follow-up . Conclusions The lifestyle intervention was not more effective than health brochures in reducing risk scores for T2DM and CVD or improving lifestyle behavior in an at-risk population .Trial registration Current Controlled Trials : IS RCT This paper describes the planning and implementation of an individualized teaching programme for patients and their families following primary uncomplicated myocardial infa rct ion . This preliminary study was design ed and implemented by a senior nurse while working in the clinical area . Patients were r and omly allocated to a control or study group . Both groups of patients were interviewed on the fourth day following admission to hospital and again at 2 and 6 months after discharge . Nurse intervention in the form of individually planned consecutive teaching sessions achieved a reduction in anxiety and modification of identifiable risk factors ( smoking , obesity , diet , exercise ) in the patients included in the teaching programme BACKGROUND This study examined the 1-year effects of a minimal-contact smoking cessation intervention for cardiac in patients . METHODS The multicenter study included cardiac in patients who had smoked prior to hospitalization . A pretest-posttest quasi-experimental design was used . Patients ' experimental condition depended on the hospital they were assigned to . The design was partially r and omized : 4 of the 11 hospitals selected the experimental condition themselves ( 2 experimental , 2 control ) , while the remaining 7 hospitals were r and omly assigned . The experimental group consisted of patients of 5 hospitals ( N = 388 ) . Patients of 6 other hospitals served as the control group ( N = 401 ) . The intervention included stop-smoking advice by the cardiologist , brief counseling by the nurse , the provision of self-help material s , and aftercare by the cardiologist . RESULTS Logistic regression analyses controlling for baseline differences and covariates did not show significant intervention effects on point prevalence and continuous abstinence . The study also showed that the outcomes were not significantly related to the way hospitals were assigned to the experimental condition . CONCLUSIONS While short-term effects were found , the minimal-contact intervention did not result in significant effects after 12 months , at least if patients lost to follow-up were treated as posttest smokers . Efforts should be made to improve the intervention , especially the aftercare Objective . To evaluate an intervention programme on smoking cessation in patients with diabetes mellitus in primary healthcare . Design . Regional controlled intervention study . Setting . Seventeen primary healthcare centres in Sweden . Intervention . In the intervention centres , nurses with education in diabetes were given one half-day of training in motivational interviewing and smoking cessation . An invitation to participate in a smoking cessation group was mailed to patients from the intervention centres followed by a telephone call from the patient 's diabetes nurse . The nurses who intervened were specially educated in smoking cessation . The control group received a letter containing advice to stop smoking and information about a one-year follow-up . Patients . Daily smokers with diabetes mellitus , 30–75 years of age . In the intervention centres 241 patients fulfilled the criteria and in the control centres 171 patients . Main outcome measures . Self-reported smoking habits after one year . Results . In total , 21 % of the smokers accepted group treatment . After 12 months , 20 % ( 42/211 ) in the intervention centres reported that they had stopped smoking and 7 % ( 10/140 ) in the control centres ; 40 % ( 19/47 ) of the smokers who had participated in group treatment reported that they had stopped smoking . Conclusion . A computerized record system for patients in primary healthcare was used to identify diabetic patients who were smokers . The selected group was invited to a stop smoking programme . At a one-year follow-up significantly more patients in the intervention centres had stopped smoking compared with patients in the control centres Purpose . Assess the effectiveness of a two-step health education program by nurses delivered through nonsmoking mothers to help fathers of sick children quit smoking . Design . R and omized , controlled trial . Setting . General pediatric wards of four major hospitals in Hong Kong . Subjects . Nonsmoking mothers who had a live-in smoking spouse were recruited when they brought sick children to the hospital . A total of 752 mothers were r and omized into the intervention arm and 731 into the control arm . Intervention . The intervention group received st and ardized health advice , behavior modification booklets , and a 1–week telephone reminder . The control group received usual care . Measurements . The main outcome measure was the quit rate ( 7–day point prevalence ) of smoking fathers as determined by telephone follow-up with mothers at 3 and 12 months . Quit attempts and smoking reduction were secondary outcome measures . Results . At 3 months , more fathers in the intervention group had quit smoking ( 7.4 % vs. 4.8 % ; p = .03 ) , reduced daily cigarette consumption by 50 % or more ( 30.6 % vs. 22.6 % ; p < .001 ) , and reported quit attempts ( 6.5 % vs. 3.6 % ; p = .01 ) . The differences were not statistically significant by 12 months . Conclusion . A simple health education intervention provided by nurses to mothers of sick children has a short-term effect in helping smoking fathers quit , reduce consumption , and trigger quit attempts . Future studies should confirm the longer-term sustainability of the effect Abstract Objective . To study the effectiveness of a comprehensive diabetes programme in general practice that integrates patient-centred lifestyle counselling into structured diabetes care . Design and setting . Cluster r and omised trial in general practice s. Intervention . Nurse-led structured diabetes care with a protocol , record keeping , reminders , and feedback , plus training in motivational interviewing and agenda setting . Subjects . Primary care nurses in 58 general practice s and their 940 type 2 diabetes patients with an HbA1c concentration above 7 % , and a body mass index ( BMI ) above 25 kg/m2 . Main outcome measures . HbA1c , diet , and physical activity ( medical records and patient question naires ) . Results . Multilevel linear and logistic regression analyses adjusted for baseline outcomes showed that despite active nurse participation in the intervention , the comprehensive programme was no more effective than usual care after 14 months , as shown by HbA1c levels ( difference between groups = 0.13 ; CI 20.8–0.35 ) and diet ( fat ( difference between groups = 0.19 ; CI 20.82–1.21 ) ; vegetables ( difference between groups = 0.10 ; CI-0.21–0.41 ) ; fruit ( difference between groups = 20.02 ; CI 20.26–0.22 ) ) , and physical activity ( difference between groups = 21.15 ; CI 212.26–9.97 ) , or any of the other measures of clinical parameters , patient 's readiness to change , or quality of life . Conclusion . A comprehensive programme that integrated lifestyle counselling based on motivational interviewing principles integrated into structured diabetes care did not alter HbA1c or the lifestyle related to diet and physical activity . We thus question the impact of motivational interviewing in terms of its ability to improve routine diabetes care in general practice Background This study will test the uptake and effectiveness of a flexible package of smoking cessation support provided primarily by the practice nurse ( PN ) and tailored to meet the needs of a diversity of patients . Methods / Design This study is a cluster r and omised trial , with practice s allocated to one of three groups 1 ) Quit with Practice Nurse 2 ) Quitline referral 3 ) GP usual care . PNs from practice s r and omised to the intervention group will receive a training course in smoking cessation followed by access to mentoring . GPs from practice s r and omised to the Quitline referral group will receive information about the study and the process of written referral and GPs in the usual care group will receive information about the study . Eligible patients are those aged 18 and over presenting to their GP who are daily or weekly smokers and who are able to give informed consent . Patients on low incomes in all three groups will be able to access free nicotine patches . Primary outcomes are sustained abstinence and point prevalence abstinence at the three month and 12 month follow-up points ; and incremental cost effectiveness ratios at 12 months . Process evaluation on the reach and acceptability of the intervention approached will be collected through Computer Assisted Telephone Interviews ( CATI ) with patients and semi-structured interviews with PNs and GPs . The primary analysis will be by intention to treat . Cessation outcomes will be compared between the three arms at three months and 12 month follow-up using multiple logistic regression . The incremental cost effectiveness ratios will be estimated for the 12 month quit rate for the intervention groups compared to usual care and to each other . Analysis of qualitative data on process outcomes will be based on thematic analysis . Discussion High quality evidence on effectiveness of practice nurse interventions is needed to inform health policy on development of practice nurse roles . If effective , flexible support from the PN in partnership with the GP and the Quitline could become the preferred model for providing smoking cessation advice in Australian general practice .Trial Registration Objective To evaluate whether nurse run clinics in general practice improve secondary prevention in patients with coronary heart disease . Design R and omised controlled trial . Setting A r and om sample of 19 general practice s in northeast Scotl and . Patients 1173 patients ( 685 men and 488 women ) under 80 years with working diagnoses of coronary heart disease , but without terminal illness or dementia and not housebound . Intervention Nurse run clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow up . Main outcome measures Components of secondary prevention assessed at baseline and one year were : aspirin use ; blood pressure management ; lipid management ; physical activity ; dietary fat ; and smoking status . A cumulative score was generated by counting the number of appropriate components of secondary prevention for each patient . Results There were significant improvements in aspirin management ( odds ratio 3.22 , 95 % confidence interval 2.15 to 4.80 ) , blood pressure management ( 5.32 , 3.01 to 9.41 ) , lipid management ( 3.19 , 2.39 to 4.26 ) , physical activity ( 1.67 , 1.23 to 2.26 ) and diet ( 1.47 , 1.10 to 1.96 ) . There was no effect on smoking cessation ( 0.78 , 0.47 to 1.28 ) . Of six possible components of secondary prevention , the baseline mean was 3.27 . The adjusted mean improvement attributable to intervention was 0.55 of a component ( 0.44 to 0.67 ) . Improvement was found regardless of practice baseline performance . Conclusions Nurse run clinics proved practical to implement in general practice and effectively increased secondary prevention in coronary heart disease . Most patients gained at least one effective component of secondary prevention and , for them , future cardiovascular events and mortality could be reduced by up to a third Objective . To investigate the effect of a primary care model for COPD on process of care and patient outcome . Design . Controlled study with delayed intervention in control group . Setting . The GP delegates tasks to a COPD support service ( CSS ) and a practice nurse . The CSS offers logistic support to the practice through a patient register and recall system for annual history-taking and lung function measurement . It also forms the link with the chest physician for diagnostic and therapeutic advice . The practice nurse 's most important tasks are education and counselling . Subjects . A total of 44 practice s ( n = 22 for intervention and n = 22 for control group ) and 260 of their patients ≥40 years with obstructive lung diseases . Results . Within the intervention group planned visits increased from 16 % to 44 % and from 19 % to 25 % in the control condition ( difference between groups p = 0.014 ) . Annual lung function measurement rose from 17 % to 67 % in the intervention and from 11 % to 18 % in the control group ( difference between groups p = 0.001 ) . Compared with control , more but not statistically significant smokers received periodic advice to quit smoking ( p = 0.16 ) . At baseline 41 % of the intervention group were using their inhalers correctly and this increased to 54 % after two years ; it decreased in the control group from 47 to 29 % ( difference between groups p = 0.002 ) . The percentage of patients without exacerbation did not change significantly compared with the control condition . The percentage of the intervention group not needing emergency medication rose from 79 % to 84 % but decreased in the controls from 81 to 76 % ( difference between groups p = 0.08 ) . Conclusion . Combining different disciplines in one model has a positive effect on compliance with recommendations for monitoring patients , and improves the care process and some patient outcomes OBJECTIVE To evaluate two counseling programs in general practice to help smokers with chronic obstructive pulmonary disease ( COPD ) to quit smoking . METHODS Cluster r and omized controlled trial including 68 general practice s ( 667 patients ) using a r and omly assigned intervention program with counseling and advice about nicotine replacement therapy ( and additional bupropion-SR in one of the programs ) or usual care . Usual care consisted of periodic regular check-ups and COPD information . The main outcome measure was biochemically verified point prevalence at 12 months . RESULTS The two intervention groups were treated as one in the analysis because they were equally effective . The intervention result ed in a significantly self-reported higher success rate ( 14.5 % ) compared to usual care ( 7.4 % ) ; odds ratio=2.1 , 95 % confidence interval=1.1 - 4.1 . Biochemically verified quit rates were 7.5 % ( intervention ) and 3.4 % ( usual care ) ; odds ratio=2.3 , 95 % confidence interval=0.9 - 6.0 . CONCLUSION The program doubled the cessation rates ( statistically nonsignificant ) . Too few participants used the additional bupropion-SR to prove its effectiveness . PRACTICE IMPLICATION S The protocol s can be used for COPD patients in general practice , but expectations should be modest . If quitting is unsuccessful , a stepped care approach should be considered Chronic obstructive pulmonary disease ( COPD ) is disabling , with symptoms such as chronic cough , phlegm , wheezing , shortness of breath and increased infections of the respiratory passage . The aim was to examine the effects of a structured educational intervention programme at a nurse-led primary health care clinic ( PHCC ) on quality of life ( QoL ) , knowledge about COPD and smoking cessation in patients with COPD . This study had an experimental design in which 52 patients with COPD from a Swedish primary care setting were r and omized into two groups ( intervention or control ) . Both groups received st and ard care but patients in the intervention group were also offered two visits to a nurse specialized in COPD care . The purpose of the visits was to increase the patients ' self-care ability and their knowledge about COPD . The study was approved by the local Research Ethics Committee . Data were collected using two question naires , one pertaining to knowledge about COPD and smoking habits and St. George 's Respiratory Question naire , addressing how QoL was affected by the patients ' respiratory symptoms . The intervention and control groups answered both question naires on their first and last visits to the PHCC . A statistically significant increase was noted in the intervention group on QoL , the number of patients who stopped smoking and patients ' knowledge about COPD at the follow-up , 3 - 5 months after intervention . However , a confounding factor may have been that one of the research ers ( Eva Osterlund Efr aims son ) , as a nurse in the PHCC , performed the intervention . This implies that patients were in a dependent relationship which may have affected the responses in a favourable direction . Our findings show that conventional care alone did not have an effect on patients ' QoL and smoking habits . Instead , the evidence suggests that a structured programme with self-care education is needed to motivate patients for life-style changes This pilot study evaluated the effectiveness of a nurse-delivered home-visiting program during the postpartum period that included a low-intensity smoking relapse-prevention intervention . A prospect i ve two-group design was used . Participants were women who had quit smoking during their pregnancy . They were invited to participate during postpartum hospitalization on a university hospital postpartum ward . A brief intervention during postpartum hospitalization , a home visit , and two follow-up phone calls over a 1- to 2-month period were compared with a routine home visit without any prescribed focus on tobacco use . The main outcome was biochemically verified smoking abstinence at 3 and 6 months postenrollment . Abstinence was defined as a salivary cotinine level of 14 ng/ml or less . At 3 months postenrollment , 26.4 % of the intervention group were classified as abstinent , compared with 12.4 % of the comparison group ( OR = 2.4 , 95 % CI = 1.16 - 4.98 ) . At 6 months , the proportion of the intervention group categorized as abstinent was 21.5 % , compared with 10.2 % of comparison group participants ( OR = 2.5 , 95 % CI = 1.13 - 5.71 ) . Greater than three times as many in the intervention group remained abstinent at both times ( 18.2 % ) , compared with the comparison group ( 5.2 % ; OR = 2.4 , 95 % CI = 1.16 - 4.93 ) . The effectiveness of this brief , low-cost , and potentially replicable intervention in improving the rate of persistent postpartum smoke-free status for women who quit smoking during pregnancy is encouraging . A r and omized trial of the approach is warranted Practice nurses are playing an increasingly prominent role in preventive care , including the provision of anti-smoking advice during routine health checks . A r and omized controlled trial was design ed to assess the effectiveness of anti-smoking advice provided by nurses in helping smokers to stop smoking . A total of 14,830 patients aged 16 - 65 years from 11 general practice s completed a brief question naire on general health , including smoking status , at surgery attendance . The doctor identified 4330 smokers and r and omly allocated 4210 to control or intervention groups . The doctor asked those in the intervention group to make an appointment with the practice nurse for a health check . The attendance rate at the health check was 26 % . Smokers were sent follow-up question naires at one month and one year , and those who did not respond to two reminders were assumed to have continued to smoke . There was no significant difference in reported cessation between the intervention and control groups at one month or one year . However , there was a significant difference in the proportion of patients who reported giving up within one month and who had not lapsed by one year--0.9 % in controls and 3.6 % in the intervention group ( P less than 0.01 ) . Nevertheless , the effect of the nurse intervention itself may be small as the sustained cessation rate in attenders was only 42.4 % higher than in non-attenders . The deception rate in reporting cessation , as measured by urinary cotinine , was of the order of 25 % AIM To investigate the effects of a nurse-led multidisciplinary programme ( NMP ) of pulmonary rehabilitation in primary health care with regard to functional capacity , quality of life ( QoL ) , and exacerbations among patients with chronic obstructive pulmonary disease ( COPD ) . METHOD A 1-year longitudinal study with a quasi-experimental design was undertaken in patients with COPD , 49 in the intervention group and 54 in the control group . Functional capacity was assessed using the 6-minute walking test , and quality of life ( QoL ) was assessed using the Clinical COPD Question naire . Exacerbations were calculated by examination of patient records . RESULTS No significant differences were found between the groups in functional capacity and QoL after 1 year . The exacerbations decreased in the intervention group ( n = -0.2 ) and increased in the control group ( n = 0.3 ) during the year after NMP . The mean difference of change in exacerbation frequency between the groups was statistically significant after one year ( p=0.009 ) . CONCLUSIONS The NMP in primary care produced a significant reduction in exacerbation frequency , but functional capacity and QoL were unchanged . More and larger studies are needed to evaluate potential benefits in functional capacity and Coronary artery diseases ( CAD ) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events . The development and evaluation of secondary prevention programmes therefore an important task . This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital , Malmö , Sweden . Four weeks after discharge from the hospital , consecutive male and female patients aged 50 - 70 years with acute myocardial infa rct ion ( AMI ) or treated with coronary artery bypass grafting ( CABG ) surgery were r and omised to a hospital organised preventive intervention or to usual follow-up at their general practitioners . In the three studies using this r and omised design , 87 ( study II ) , 90 ( study IV ) , and 106 ( study V ) intervention patients were available for evaluation . In addition , without r and omisation , lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients ( study I ) , and quality of life ( QL ) were estimated by question naire at one month and at one year after the event in 266 AMI , 94 CABG , and 16 percutaneous transluminal coronary angioplasty ( PTCA ) patients ( study III ) . The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients ( study II ) . The intervention also did not show any significant improvement in working capacity in AMI and CABG patients . However , working capacity improved in both intervention and reference CABG patients , most probably due to improved coronary circulation from the surgery ( study IV ) . Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients . This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients ( study V ) . The prevention programme also decreased body mass index significantly in AMI but not in CABG patients ( study V ) . In AMI patients receiving thrombolysis , cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal . In AMI patients not receiving thrombolysis , the lipid estimates from four weeks after the event were slightly , but significantly , above the within 24 hours from onset of symptoms estimates ( study I ) . One month after the event , both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls . One year after the event , patients differed from controls mainly in somatic symptoms ( study III ) . Thus , the intervention programme was most successful in affecting lipid levels and food habits in AMI patients . QL was considerably affected in patients following an cardiac event , especially during the initial recovery phase . In addition , in patients receiving thrombolysis , cholesterol levels estimated four weeks after an AMI are reasonably valid estimates of baseline values and may be used to decide about lipid lowering interventions Objectives : The purpose of this study was to evaluate a nurse-managed , lay-led tobacco cessation intervention delivered to adult women in Ohio Appalachia . Methods : A r and omized controlled experimental design included intervention participants ( n = 147 ) enrolled in a nurse-managed , lay-led protocol that incorporated nicotine replacement and behavioral counseling . Control participants ( n = 155 ) received a personalized letter from their clinic physician , who advised them to quit smoking and requested they schedule a clinic appointment to discuss cessation . Results : Self-reported and cotinine-vali date d quit rates were significantly higher among intervention group participants compared with control group participants at 3- and 6-month follow-up ( P < 0.02 ) . At 12 months , self-reported abstinence was 19.1 % ( intervention group ) and 9.0 % ( control group ) , with cotinine-vali date d rates of 12.2 % and 7.1 % , respectively ( P = 0.13 ) . Prolonged abstinence rates were significantly different between groups at 3 , 6 , and 12 months ( P < 0.02 ) . Logistic regression analyses indicated adjusted odds of cotinine-vali date d quitting was associated with cigarette consumption per day ( odds ratio , 0.94 ; 95 % confidence interval , 0.89 - 0.99 ) and Center for Epidemiologic Studies Depression Scale score ≥ 16 ( odds ratio , 0.39 ; 95 % confidence interval , 0.17 - 0.90 ) . Conclusions : A lay-led approach that is managed by a nurse may serve as an effective cessation strategy among this high-risk population . Additional efforts are needed to sustain long-term abstinence , even after intensive intervention . ( Cancer Epidemiol Biomarkers Prev 2009;18(12):3451–8 Public health and hospital nurses have widespread contact with smokers ; an effective smoking cessation program administered by nurses has tremendous potential . This study evaluated : 1 ) the effectiveness of the self-help cessation program , " Time to Quit"/"Moi aussi , j'écrase " ( TTQ ) , provided on a one-to-one basis ; and 2 ) a smoking cessation training program for baccalaureate nursing students . Nursing students recruited 307 smokers who were r and omly assigned to receive one of two interventions . Control smokers received a list of community smoking cessation re sources and experimental subjects received this list plus TTQ . Smoking self-reports and cotinine levels were obtained at baseline , six weeks and nine months . More smokers receiving TTQ had reduced at six weeks post-intervention , while there were no differences in quit or reduction rates at the nine-month follow-up . Students were positive about learning the techniques and their knowledge scores were significantly higher than those of non-participating students OBJECTIVES This article describes the demographic , psychosocial , and medical characteristics and smoking patterns of women hospitalized with cardiovascular disease ( CVD ) enrolled in the Women 's Initiative for Nonsmoking ( WINS ) trial . DESIGN Study design is a r and omized clinical trial with cross-sectional baseline data . SETTING Women enrolled during a 27-month period from 10 hospitals in the San Francisco Bay Area . PARTICIPANTS Subjects included 277 women . RESULTS The women 's ages ranged from 33 to 86 years , with a mean age of 60.7 ( + /-10 ) years . Most ( 51 % ) were college graduates , had attended some college or had postgraduate degrees ; 40 % were married ; 76 % were white . Median income was between 30,000 dollars and 35,000 , but 27 % of the women had incomes less than 15,000 dollars per year . The women smoked a median of 20 cigarettes per day ( range , 1 - 90 ) . Median age when women began smoking was 18.6 years ; average number of years smoked was 40 ; and 78 % had made more than 2 previous attempts to quit . On a 10-point scale , 71 % of the women rated their confidence to quit smoking ( self-efficacy ) as 5 or greater . According to the Burnam Depression Screener , 56.7 % were depressed . CONCLUSIONS This is the largest study describing the smoking patterns of women hospitalized with CVD . These women were older , white , had smoked for many years , were moderately to highly addicted to tobacco , had few financial re sources , and a large proportion were depressed . These important psychosocial factors need to be taken into account when planning smoking cessation interventions for women with CVD Women 's Initiative for Nonsmoking ( WINS ) is a r and omized clinical trial design ed to test the efficacy of a nurse-managed smoking cessation and relapse prevention intervention design ed specifically for women . The WINS intervention is rooted in social learning theory , specifically that of self-efficacy . It is a multimedia approach that provides education , counseling , and telephone follow-up that meet the smoking cessation intervention guidelines established by the Agency for Health Care Policy and Research . The WINS intervention has been successfully implemented in more than 140 women and has proven to be feasible and well accepted by both the women and their health care providers . Although the intervention in the protocol -driven r and omized clinical trial was begun in the hospital , it is anticipated that nurses in any setting , inpatient or outpatient , who serve population s at risk for cardiovascular disease , peripheral vascular disease , lung cancer , or pulmonary disease could successfully provide the intervention This article describes the design and methods of the Women 's Initiative for Nonsmoking , a nurse-managed intervention for smoking cessation and relapse prevention in women hospitalized with cardiovascular disease . The Women 's Initiative for Nonsmoking is a r and omized clinical trial with a 3-month intervention period and follow-up at 6 , 12 , 24 , and 30 months . Data were collected at 10 urban hospitals in the San Francisco Bay area . The sample consisted of 278 women , mean age 61 years , hospitalized with cardiovascular disease ( angina , myocardial infa rct ion , angioplasty , coronary artery bypass graft surgery , heart failure , valvular disease , peripheral vascular disease , and cerebrovascular disease ) . The behavioral intervention consisted of nurse-managed care focused on preventing relapse after smoking cessation during hospitalization . Measures included demographic , clinical ( includes diagnosis and comorbidity data ) , smoking history , confidence question naire , stress , depression , and quality of life . This article provides a detailed description of research design and methods for research ers desiring to replicate the study and nurse practitioners developing a smoking cessation , risk-reduction program in the clinical setting . Results of the trial are forthcoming Abstract Objective : To determine the effectiveness of health checks , performed by nurses in primary care , in reducing risk factors for cardiovascular disease and cancer . Design : R and omised controlled trial . Setting : Five urban general practice s in Bedfordshire . Subjects : 2205 men and women who were r and omly allocated a first health check in 1989 - 90 and a re-examination in 1992 - 3 ( the intervention group ) ; 1916 men and women who were r and omly allocated an initial health check in 1992 - 3 ( the control group ) . All subjects were aged 35 - 64 at recruitment in 1989 . Main outcome measures : Serum total cholesterol concentration , blood pressure , body mass index , and smoking prevalence ( with biochemical validation of cessation ) ; self reported dietary , exercise , and alcohol habits . Results : Mean serum total cholesterol was 3.1 % lower in the intervention group than controls ( difference 0.19 mmol/l ( 95 % confidence interval 0.12 to 0.26 ) ; in women it was 4.5 % lower ( P<0.0001 ) and in men 1.6 % ( P<0.05 ) , a significant difference between the sexes ( P<0.01 ) . Self reported saturated fat intake was also significantly lower in the intervention group . Systolic and diastolic blood pressures and body mass index were respectively 1.9 % , 1.9 % , and 1.4 % lower in the intervention group ( P<0.005 in all cases ) . There was a 3.9 % ( 2.4 to 5.3 ) difference in the percentage of subjects with a cholesterol concentration > /=8 mmol/l , but no significant differences in the number with diastolic blood pressure > /=100 mm Hg or body mass index > /=30 kg/m2 . There was no significant difference between the two groups in prevalence of smoking or excessive alcohol use . Annual rechecks were no more effective than a single recheck at three years , but health checks led to a significant increase in visits to the nurse according to patients ' degree of cardiovascular risk . Conclusions : The benefits of health checks were sustained over three years . The main effects were to promote dietary change and reduce cholesterol concentrations ; small differences in blood pressure may have been attributable to accommodation to measurement . The benefits of systematic health promotion in primary care are real , but must be weighed against the costs in relation to other priorities . Key messages Key messages There is little effect on smoking or alcohol use , and more targeted approaches to modifying these behaviours may be appropriate Systematic implementation of health checks might lead to a reduction in risk of myocardial infa rct ion among those who attend of about 5 - 15 % ; men , who are at higher risk , show less change than women Health checks consume substantial re sources , and their effect is attenuated by non-attendance The benefits of health promotion through primary care must be weighed against their costs and in relation to other The aim of this study is to assess the potential effectiveness , acceptability and feasibility of a brief smoking cessation intervention delivered as part of cervical screening . A cluster r and omised controlled trial was conducted with clinic week as the unit of r and omisation , comparing a group ( n=121 ) receiving brief smoking cessation advice supplemented with written information given by practice nurses during cervical smear test appointments , with a group ( n=121 ) not receiving this advice . Outcomes were intention to stop smoking ( potential effectiveness ) ; intention to attend for future cervical screening ( acceptability ) ; duration of intervention ( feasibility ) . 172/242 ( 71 % ) and 153/242 ( 63 % ) participants completed 2-week and 10-week follow-ups , respectively . Compared to women in the control group , those in the intervention group had higher intentions to stop smoking at 2-weeks ( adjusted mean difference 0.51 , 95 % CI : −0.02 to 1.03 , P=0.06 ) and 10-weeks ( adjusted mean difference 0.80 , 95 % CI 0.10 to 1.50 , P=0.03 ) . The two groups had similarly high intentions to attend for future screening . Consultations in the intervention arm took a mean of 4.98 min ( 95 % CI : 3.69 to 6.27 ; P<0.001 ) longer than the control arm . In conclusion , brief smoking cessation advice given by practice nurses as part of cervical screening seems acceptable , feasible and potentially effective . Evidence is lacking on the effectiveness and cost effectiveness of this intervention in achieving biochemically vali date d smoking cessation BACKGROUND Smokers hospitalized with acute coronary syndrome ( ACS ) are at high risk for subsequent ischemic events . Nevertheless , over two-thirds of patients continue to smoke after an acute myocardial infa rct ion . Bupropion hydrochloride has proven efficacy as a smoking cessation aid , but data regarding its safety and efficacy in ACS patients are limited . METHODS In a double-blind , r and omized controlled trial , we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release ( SR ) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support . Primary efficacy outcome was smoking abstinence at 1 year . Primary safety outcome was clinical events at 1 year . RESULTS A total of 151 patients were enrolled ; all but 2 completed follow-up . Abstinence rates at 3 months were 45 % and 44 % in the bupropion SR and placebo groups , respectively ( P = .99 ) ; 37 % vs 42 % ( P = .61 ) at 6 months ; and 31 % vs 33 % ( P = .86 ) at 1 year . On multivariate analysis , an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year ( odds ratio [ OR ] , 4.2 ; 95 % confidence interval [ CI ] , 1.22 - 14.19 ) . Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation ( OR , 0.23 ; 95 % CI , 0.07 - 0.78 ) . Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index , but dizziness was more common compared with placebo ( 14 % vs 1.4 % ; P = .005 ) . CONCLUSION In hospitalized patients with ACS who received continuous , intensive nurse counseling about smoking cessation , bupropion did not increase the rates of smoking abstinence Background The use of spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) is still an issue of debate , particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation . We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed " confrontational counselling " ; a patient-centred approach which involves specific communication skills and elements of cognitive therapy . An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions . The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation . Methods / Design The study design is a r and omized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( experimental group ) , health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( control group 1 ) , and " care as usual " delivered by the GP ( control group 2 ) . Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry . Due to a comparable baseline risk of airflow limitation and motivation to quit smoking , and because of the st and ardization of number , duration , and scheduling of counselling sessions between the experimental group and control group 1 , the study enables to assess the " net " effect of confrontational counselling . The study has been ethically approved and registered . Discussion Ethical as well as method ological considerations of the study are discussed in this protocol . A significant and relevant effect of confrontational counselling would provide an argument in favour of early detection of current smokers with airflow limitation . Successful treatment of tobacco dependence in respiratory patients requires repeated intensive interventions . The results of this study may also show that respiratory nurses are able to deliver this treatment and that intensive smoking cessation counselling is more feasible . Trial registration : Netherl and s Trial Register ( IS RCT N 64481813 ) AIMS AND OBJECTIVES To evaluate the one-year prognosis of a lifestyle counselling intervention ( diet , smoking cessation and exercise ) among patients who had open heart surgery . BACKGROUND Cardiovascular disease is the leading cause of morbidity worldwide in both developing and developed countries . Lifestyle modification plays an important role for patients who are at a high risk of developing cardiovascular disease and for those with an established cardiovascular disease . DESIGN R and omised , nonblind and lifestyle counselling intervention study with a one-year follow-up . METHODS A r and omised , nonblind intervention study was performed on 500 patients who had open heart surgery . After hospital discharge , 250 patients ( intervention group ) were r and omly allocated lifestyle counselling according to the recent guidelines provided by the European Society of Cardiology ( European Journal Preventive Cardiology , 19 , 2012 , 585 ) . The remaining 250 patients ( control group ) received the regular instructions . Primary end-point was the development of a cardiovascular disease ( nonfatal event ) during the first year ; secondary end-points included fatal events , smoking abstinence , dietary habits and a physical activity evaluation . RESULTS According to the primary end-point , the odds of having a nonfatal cardiovascular disease event are 0·56-times ( 95%CI 0·28 , 0·96 , p = 0·03 ) lower for the intervention group compared to the control group . One-year after surgery , it was found that participants in the intervention group were 1·96-times ( 95%CI 1·31 , 2·93 , p < 0·001 ) more likely to achieve dietary recommendations , 3·32-times ( 95%CI 2·24 , 4·91 , p < 0·001 ) more likely to achieve physical activity recommendations and 1·34-times ( 95%CI 1·15 , 1·56 , p < 0·001 ) more likely to return to work . CONCLUSION Lifestyle counselling intervention following open heart surgery can improve health outcomes and reduce the risk of a new cardiac event . Health care services must recommend and organise well-structured cardiac rehabilitation programmes adjusted to the patient 's needs . RELEVANCE TO CLINICAL PRACTICE A well-structured cardiac rehabilitation programme adjusted to the patient 's profile is a safe and cost-effective way to improve patients ' outcome Background There is a considerable body of evidence on the effectiveness of specific interventions in individuals who wish to quit smoking . However , there are no large-scale studies testing the whole range of interventions currently recommended for helping people to give up smoking ; specifically those interventions that include motivational interviews for individuals who are not interested in quitting smoking in the immediate to short term . Furthermore , many of the published studies were undertaken in specialized units or by a small group of motivated primary care centres . The objective of the study is to evaluate the effectiveness of a stepped smoking cessation intervention based on a trans-theoretical model of change , applied to an extensive group of Primary Care Centres ( PCC ) . Methods / Design Cluster r and omised clinical trial . Unit of r and omization : basic unit of care consisting of a family physician and a nurse , both of whom care for the same population ( aprox . 2000 people ) . Intention to treat analysis . Study population : Smokers ( n = 3024 ) aged 14 to 75 years consulting for any reason to PCC and who provided written informed consent to participate in the trial . Intervention : 6-month implementation of recommendations of a Clinical Practice Guideline which includes brief motivational interviews for smokers at the precontemplation – contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help , and reinforcing intervention in the maintenance stage . Control group : usual care . Outcome measures : Self-reported abstinence confirmed by exhaled air carbon monoxide concentration of ≤ 10 parts per million . Points of assessment : end of intervention period and 1 and 2 years post-intervention ; continuous abstinence rate for 1 year ; change in smoking cessation stage ; health status measured by SF-36 . Discussion The application of a stepped intervention based on the stages of a change model is possible under real and diverse clinical practice conditions , and improves the smoking cessation success rate in smokers , besides of their intention or not to give up smoking at baseline . Trial Registration Clinical Trials.gov Identifier : Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease ( COPD ) . But a fewer smoking cessation measures were conducted in communities for smokers with COPD in China . The aim of our study was to assess the preventive effects of behavioral interventions for smoking cessation and potential impact factors in smokers with COPD in China . Methods In a r and omised controlled smoking cessation trial 3562 patients with COPD who were current smoker were allocated to intervention group received behavioral intervention and control group received the usual care for two years . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of month 24 to the end of month 30 . Participants were followed up at month 48 . Results Continuous smoking abstinence rates from month 24 to 30 were significantly higher in participants receiving behavioral intervention than in those receiving usual care ( 46.4 % vs 3.4 % , p < 0.001 ) . Continuous abstinence rates from months 24 to 36 ( 45.8 % vs 4.0 % ) and months 24 to 48 ( 44.3 % vs 5.1 % ) were also higher in participants receiving behavioral intervention than in those control group . Family members or family physicians/nurses smoking were first identified to influence smoking cessation . Conclusions Behavioral intervention doubled the smoking cessation rate in patients with COPD and was complied well by the general practitioners . The family members and family physicians/nurses smoking were the main risk factors for smoking cessation . Trial registration Chinese Clinical Trials Registration ( ChiCTR-TRC-12001958 ) Objective To quantify the impact of a practical , hospital-based nurse-coordinated prevention programme on cardiovascular risk , integrated into the routine clinical care of patients discharged after an acute coronary syndrome , as compared with usual care only . Design RESPONSE ( R and omised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists ) was a r and omised clinical trial . Setting Multicentre trial in secondary and tertiary healthcare setting s. Participants 754 patients admitted for acute coronary syndrome . Intervention A nurse-coordinated prevention programme , consisting of four outpatient nurse clinic visits , focusing on healthy lifestyles , biometric risk factors and medication adherence , in addition to usual care . Main outcome measures The main outcome was 10-year cardiovascular mortality risk as estimated by Systematic Coronary Risk Evaluation at 12 months follow-up . Secondary outcomes included Framingham Coronary Risk Score at 12 months , in addition to changes in individual risk factors . Risk factor control was classified as ‘ poor ’ if 0 to 3 factors were on target , ‘ fair ’ if 4 to 6 factors were on target , and ‘ good ’ if 7 to 9 were on target . Results The mean Systematic Coronary Risk Evaluation at 12 months was 4.4 per cent ( SD 4.5 ) in the intervention group and 5.4 per cent ( SD 6.2 ) in the control group ( p=0.021 ) , representing a 17.4 % relative risk reduction . At 12 months , risk factor control classified as ‘ good ’ was achieved in 35 % of patients in the intervention group compared with 25 % in the control group ( p=0.003 ) . Attendance to the nurse-coordinated prevention programme was 92 % . In the intervention group , 86 rehospitalisations were observed against 132 in the control group ( relative risk reduction 34.8 % , p=0.023 ) . Conclusions The nurse-coordinated hospital-based prevention programme in addition to usual care is a practical , yet effective method for reduction of cardiovascular risk in patients with coronary disease . Our data suggest that the counselling component of the programme may lead to a reduction in hospital readmissions . Trial Registration trialregister.nl Identifier TC1290 Background Recent research indicates that 35 percent of blue-collar workers in the US currently smoke while only 20 percent of white-collar workers smoke . Over the last year , we have been working with heavy equipment operators , specifically the Local 324 Training Center of the International Union of Operating Engineers , to study the epidemiology of smoking , which is 29 % compared to 21 % among the general population . For the current study funded by the National Cancer Institute ( 1R21CA152247 - 01A1 ) , we have developed the Tobacco Tactics website which will be compared to the state supported 1 - 800-QUIT-NOW telephone line . Outcome evaluation will compare those r and omized to the Tobacco Tactics web-based intervention to those r and omized to the 1 - 800-QUIT-NOW control condition on : a ) 30-day and 6-month quit rates ; b ) cotinine levels ; c ) cigarettes smoked/day ; d ) number of quit attempts ; and e ) nicotine addiction . Process evaluation will compare the two groups on the : a ) contacts with intervention ; b ) medications used ; c ) helpfulness of the nurse/coach ; and d ) willingness to recommend the intervention to others . Methods / Design This will be a r and omized controlled trial ( N = 184 ) . Both interventions will be offered during regularly scheduled safety training at Local 324 Training Center of the International Union of Operating Engineers and both will include optional provision of over-the-counter nicotine replacement therapy and the same number of telephone contacts . However , the Tobacco Tactics website has graphics tailored to Operating Engineers , tailored cessation feedback from the website , and follow up nurse counseling offered by multimedia options including phone and /or email , and /or e-community . Primary Analysis of Aim 1 will be conducted by using logistic regression to compare smoking habits ( e.g. , quit rates ) of those in the intervention arm to those in the control arm . Primary analyses for Aim 2 will compare process measures ( e.g. , medications used ) between the two groups by linear , logistic , and Poisson regression . Discussion Dissemination of an efficacious work-site , web-based smoking cessation intervention has the potential to substantially impact cancer rates among this population . Based on the outcome of this smaller study , wider scale testing in conjunction with the International Environment Technology Testing Center which services Operating Engineers across North America ( including US , Mexico , and Canada ) will be conducted . Trial registration Background Smoking is an important risk factor for cardiovascular disease ( CVD ) , and quitting is highly beneficial . Yet , less than 30 % of CVD patients stop smoking . Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease . Objective A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change . Method Participants ( N = 168 ) were r and omly assigned by cohorts to inpatient counseling with telephone follow-up , inpatient counseling , and usual care . The inpatient intervention consisted of a 1-hr counseling session , and the telephone follow-up included 6 calls during the first 2 months after discharge . The nursing intervention was tailored to the individual 's stage of change . End points at 2 and 6 months included actual and continuous smoking cessation rates ( biochemical markers ) and increased motivation ( progress to ulterior stages of change ) . Results Assuming that surviving patients lost to follow-up were smokers , the 6-month smoking abstinence rate was 41.5 % in the inpatient counseling with telephone follow-up group , compared with 30.2 % and 20 % in the inpatient counseling and usual care groups , respectively ( p = .05 ) . Progress to ulterior stages of change was 43.3 % , 32.1 % , and 18.2 % , respectively ( p = .02 ) . Stage of change at baseline and intervention predicted smoking status at 6 months . Discussion This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months , and progression to ulterior stages of change . The telephone follow-up was an important adjunct . It is , therefore , recommended to include such comprehensive smoking cessation programs within hospital setting s for individuals with CVD BACKGROUND Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children 's health problems associated with exposure to tobacco smoke . The pediatric clinic is a " teachable setting " in which to provide advice and assistance to parents who smoke . OBJECTIVE To evaluate a smoking cessation intervention for women . DESIGN Two-arm ( usual care vs intervention ) r and omized trial . SETTING Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle , Wash , area . INTERVENTION During the clinic visit , women received a motivational message from the child 's clinician , a guide to quitting smoking , and a 10-minute motivational interview with a nurse or study interventionist . Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit . PARTICIPANTS Self-identified women smokers ( n = 303 ) whose children received care at participating clinics . MAIN OUTCOME MEASURE Self-reported abstinence from smoking 12 months after enrollment in the study , defined as not smoking , even a puff , during the 7 days prior to assessment . RESULTS Response rates at 3 and 12 months were 80 % and 81 % . At both follow-ups , abstinence rates were twice as great in the intervention group as in the control group ( 7.7 % vs 3.4 % and 13.5 % vs 6.9 % , respectively ) . The 12-month difference was statistically significant . CONCLUSIONS A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers . The results encourage implementation of evidence -based clinical guidelines for smoking cessation in pediatric practice Background Second-h and smoke is a severe health hazard for children . Clinical guidelines suggest that nurses advise smoking parents to quit when they accompany their sick children to paediatric setting s , but the guidelines did not mention what nurses can do if the parents are not with the children . This study examines the effectiveness of a low-intensity , nurse-led health instructional initiative for non-smoking mothers , to motivate them to take action to help their husb and s stop smoking . Methods This was a r and omised controlled trial and 1,483 non-smoking women , who were living with husb and s who do smoke , were recruited when they accompanied with their sick children on hospital admission in general paediatic wards/outpatient departments of four hospitals in Hong Kong . The women were r and omly allocated into intervention and control groups . The former received brief health education counselling from nurses , a purpose - design ed health education booklet , a “ no smoking ” sticker , and a telephone reminder one week later ; the control group received usual care . The primary outcome was the women”s action to help their smoking husb and s stop smoking at 3- , 6- and 12-month follow-ups . Results A higher proportion of women in the intervention than the control group had taken action to help their husb and s stop smoking at the 3-month ( 76 % vs. 65 % , P < .001 ) , 6-month ( 66 % vs. 49 % , P < .001 ) and 12-month ( 52 % vs. 40 % , P < .001 ) follow-ups . Women who had received the intervention , had better knowledge of the health hazards of smoking , higher intention to take action , perceived their husb and s ’ willingness to stop/reduce smoking , had previously advised their husb and s to give up smoking , were aware of their husb and s ’ history of smoking and , were aware that their husb and s had made an earlier quit attempt and intended to help them stop smoking at the follow-ups . Conclusions A brief health education intervention by nurses in paediatric setting s can be effective in motivating the mothers of sick children to take action to help their husb and s quit smoking . We recommend adding the following to the clinical practice guidelines on treating tobacco use and dependence : ‘ Nurses should offer every non-smoking mother of a sick child brief advice to encourage their husb and s to stop smoking’.Trial registration Current Controlled Trials IS RCT N72290421 Background The prevalence of smoking in Spain is high in both men and women . The aim of our study was to evaluate the role of gender in the effectiveness of a specific smoking cessation intervention conducted in Spain . Methods This study was a secondary analysis of a cluster r and omized clinical trial in which the r and omization unit was the Basic Care Unit ( family physician and nurse who care for the same group of patients ) . The intervention consisted of a six-month period of implementing the recommendations of a Clinical Practice Guideline . A total of 2,937 current smokers at 82 Primary Care Centers in 13 different regions of Spain were included ( 2003 - 2005 ) . The success rate was measured by a six-month continued abstinence rate at the one-year follow-up . A logistic mixed-effects regression model , taking Basic Care Units as r and om-effect parameter , was performed in order to analyze gender as a predictor of smoking cessation . Results At the one-year follow-up , the six-month continuous abstinence quit rate was 9.4 % in men and 8.5 % in women ( p = 0.400 ) . The logistic mixed-effects regression model showed that women did not have a higher odds of being an ex-smoker than men after the analysis was adjusted for confounders ( OR adjusted = 0.9 , 95 % CI = 0.7 - 1.2 ) . Conclusions Gender does not appear to be a predictor of smoking cessation at the one-year follow-up in individuals presenting at Primary Care Centers . Clinical Trials.gov IdentifierNCT00125905 Abstract Objective : To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems . Design : R and omised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses . Setting : Inpatient wards in 17 hospitals in Engl and . Participants : 540 smokers admitted to hospital after myocardial infa rct ion or for cardiac bypass surgery who expressed interest in stopping smoking . Intervention : Brief verbal advice and st and ard booklet ( usual care ) . Intervention lasting 20 - 30 minutes including carbon monoxide reading , special booklet , quiz , contact with other people giving up , declaration of commitment to give up , sticker in patient 's notes ( intervention group ) . Main outcome measures : Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points . Feasibility of the intervention and delivery of its components . Results : After six weeks 151 ( 59 % ) and 159 ( 60 % ) patients remained abstinent in the control and intervention group , respectively ( P=0.84 ) . After 12 months the figures were 102 ( 41 % ) and 94 ( 37 % ) ( P=0.40 ) . Recruitment was slow , and delivery of the intervention was inconsistent , raising concerns about the feasibility of the intervention within routine care . Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it ( P<0.01 ) . Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome . Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infa rct ion . Conclusions : Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers . What is already known on this topic Stopping smoking after a serious cardiac event is associated with a significant decrease in mortality Up to 70 % of smokers who survive cardiac surgery smoke again within a year Intensive interventions delivered by dedicated staff can help cardiac patients not to start to smoke again What this study adds An intervention delivered by cardiac rehabilitation nurses within routine care during patients ' hospital stay failed to increase the number who managed to stop smoking in the long term For busy staff with competing priorities , the 30 minute intervention was also on the borderline of practicability Patients admitted after a myocardial infa rct ion were over twice as likely to give up than those admitted for a bypass Background : Smoking , alcohol use , and depression are interrelated and highly prevalent in patients with head and neck cancer , adversely affecting quality of life and survival . Smoking , alcohol , and depression share common treatments , such as cognitive behavioral therapy and antidepressants . Consequently , we developed and tested a tailored smoking , alcohol , and depression intervention for patients with head and neck cancer . Methods : Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers . Subjects were r and omized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications . Data collected included smoking , alcohol use , and depressive symptoms at baseline and at 6 months . Results : The mean age was 57 years . Most participants were male ( 84 % ) and White ( 90 % ) . About half ( 52 % ) were married , 46 % had a high school education or less , and 52 % were recruited from Veterans Affairs sites . The sample was fairly evenly distributed across three major head and neck cancer sites and over half ( 61 % ) had stage III/IV cancers . Significant differences in 6-month smoking cessation rates were noted with 47 % quitting in the intervention compared with 31 % in usual care ( P < 0.05 ) . Alcohol and depression rates improved in both groups , with no significant differences in 6-month depression and alcohol outcomes . Conclusion : Treating comorbid smoking , problem drinking , and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately . ( Cancer Epidemiol Biomarkers Prev 2006;15(11):2203–8 BACKGROUND One fifth of Canadians are smokers despite the availability of community-based smoking cessation programs . It was hypothesized that offering a post-discharge smoking cessation program to cardiac patients would decrease smoking rates at six months . METHOD This pilot r and omized study explored the feasibility , acceptability and preliminary efficacy of a smoking cessation intervention delivered by a smoking cessation nurse specialist ( SCNS ) to cardiac patients after hospital discharge . SAMPLE Participants ( N=40 ) were r and omized to either a postdischarge telephone intervention delivered weekly for the first month and then monthly until the third month ( experimental group [ EG ] ) , or referral to usual community care ( control group [ CG ] ) . FINDINGS The research ers confirmed the feasibility of recruitment and acceptability of the intervention , but dfficulty with follow-up . The intention-to-treat analysis showed similar smoking cessation rates in both groups at six months ( 25 % EG versus 30 % CG ; p = 0.72 ) . CONCLUSION An intensifed follow-up protocol , or a more intensive , comprehensive and multidisciplinary intervention might be required , given the characteristics of the smokers OBJECTIVE Within the framework of a r and omized , active treatment controlled trial , we used a mediation analysis to underst and the mechanisms by which an intervention that uses confrontation with spirometry for smoking cessation achieves its effects . METHODS Participants were 228 smokers from the general population with previously undetected chronic obstructive pulmonary disease ( COPD ) , who were detected with airflow limitation by means of spirometry . They received two equally intensive behavioural treatments by a respiratory nurse combined with nortriptyline for smoking cessation : confrontational counselling with spirometry versus conventional health education and promotion ( excluding confrontation with spirometry and COPD ) . RESULTS Cotinine vali date d abstinence rates from smoking at 5 weeks after the target quit date were 43.1 % in the confrontational counselling group versus 31.3 % in the control group ( OR=1.67 , 95%CI=0.97 - 2.87 ) . The effect of confrontational counselling on abstinence was independently mediated by the expectation of getting a serious smoking related disease in the future ( OR=1.76 , 95%CI=1.03 - 3.00 ) , self-exempting beliefs ( OR=0.42 , 95%CI=0.21 - 0.84 ) , and self-efficacy ( OR=1.38 , 95%CI=1.11 - 1.73 ) . CONCLUSION We conclude that confrontational counselling increases risk perceptions and self-efficacy , and decreases self-exempting beliefs ( risk denial ) in smokers with previously undetected COPD . These changes in mediators are associated with a higher likelihood of smoking cessation . PRACTICE IMPLICATION S Apart from the intensity , the content of smoking cessation counselling may be an important factor of success . A confrontational counselling approach as we applied may have the potential to alter smoking-related cognitions in such a way that smokers are more successful in quitting . Nurses can be trained to deliver this treatment Background : There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support . Methods : A r and omised controlled trial was performed in 26 UK general practice s. 925 smokers of ⩾10 cigarettes per day were r and omly allocated to basic or weekly support . All participants were seen before quitting , telephoned around quit day , and seen 1 and 4 weeks after the initial appointment ( basic support ) . Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts . 15 mg/16 h nicotine patches were given to all participants . The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4 , 12 , 26 and 52 weeks after quit day . Results : Of the 469 and 456 participants in the basic and weekly arms , the numbers ( % ) who quit and the percentage difference were 105 ( 22.4 % ) vs 102 ( 22.4 % ) , 0.1 % ( 95 % CI −5.3 % to 5.5 % ) at 4 weeks , 66 ( 14.1 % ) vs 52 ( 11.4 % ) , −2.6 % ( 95 % CI −6.9 % to 1.7 % ) at 12 weeks , 50 ( 10.7 % ) vs 40 ( 8.8 % ) , −1.9 % ( 95 % CI −5.7 % to 2.0 % ) at 26 weeks and 36 ( 7.7 % ) vs 30 ( 6.6 % ) , −1.1 % ( 95 % CI −4.4 % to 2.3 % ) at 52 weeks . Conclusions : The absolute quit rates achieved are those expected from nicotine replacement alone , implying that neither basic nor weekly support were effective . Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately , and those in need of support should be referred to specialists OBJECTIVE To examine the effect of a nurse-delivered smoking cessation intervention on short-term smoking abstinence among hospitalized postoperative patients . DESIGN Prospect i ve , experimental , r and om assignment . SETTING Midwestern university-affiliated tertiary medical center . PATIENTS Postoperative smokers ( n = 80 ) from cardiovascular , oncology , and general surgical units . OUTCOME MEASURE Self-reported smoking status and saliva cotinine level at 5 to 6 weeks after hospitalization . INTERVENTION Three structured smoking cessation sessions during hospitalization , followed by phone calls once a week for 5 weeks after discharge . RESULTS Of the experimental group patients , 37.8 % were abstinent as compared to 25.6 % in the usual care group . Abstinence rates of experimental group patients from cardiovascular ( 40 % ) and oncology ( 64.3 % ) units were higher than that of GS ( 13.3 % ) unit patients . Regardless of group assignment , 100 % of cardiovascular and oncology patients abstained during hospitalization , compared to only 10.7 % of GS patients . CONCLUSIONS Preliminary results indicate that a nurse-delivered cessation intervention may be effective postoperatively among smokers with an identified smoking-related diagnosis Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit , yet the relative value of nurse vs physician counseling has not been explored in depth . In this study , 425 smokers attending three urban primary care centers in Barcelona were systematic ally allocated to one of three groups : group A patients received a brief counseling session to quit from their family physician ; group B patients were given the same brief counseling along with a free supply of nicotine gum ; group C received a brief health-education session from the primary care nurse . Three hundred forty-nine patients ( 82 % ) could be reached by telephone at the two-month follow up . By that time , after correcting for the estimated validity of the phone report of smoking status , the proportion declaring themselves to be nonsmokers was 10.9 % , 11.1 % , and 10.8 % , respectively , without significant differences between them . At one-year follow up the proportions were 4.4 % , 5.3 % , and 6.0 % . In the logistic regression analysis , only the expected difficulty of quitting was predictive of one-year abstention , OR = 3.1 ( 95 % CI : 1.3 - 7.3 ) . The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group Background Providing information is an important part of st and ard care and treatment for acute myocardial infa rct ion in patients . Evidence exists indicating that acute myocardial infa rct ion patients experience an information gap in the period immediately after discharge from the hospital . The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infa rct ion after their discharge from hospital . Design and method A prospect i ve r and omized , controlled trial with a 6-month follow-up was conducted . A total of 288 patients were allocated to either an intervention group ( n = 156 ) or a control group ( n = 132 ) . The latter received routine post-discharge care . The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey . Secondary endpoints included smoking and exercise habits . Results In both groups , health-related quality of life improved significantly over time on most subscales . A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale ( P=0.034 ) after 6 months . No difference was found between the groups on the Mental Health Component Summary Scale . We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months ( P=0.004 ) . More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up ( P=0.055 ) . Conclusion A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients . Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infa rct ion This paper presents a pilot study evaluating a smoking cessation programme , implemented by a nurse , in surgical pre-admission clinics at The Chesterfield and North Derbyshire Royal Hospital NHS Trust , Chesterfield , Engl and . Using a quasi-experimental design , a convenience sample of 60 subjects who smoked were r and omized , 30 to a control and 30 to a treatment group . Those in the treatment group received a variety of educational interventions and self- assessment question naires relating to smoking cessation , when attending the clinic . The control group received routine information . Data were collected using the combined interview and question naire method . There was a significant increase in positive behaviour on admission to hospital in the treatment group ( 80 % stopped or reduced smoking ) , compared to a control group ( 50 % stopped or reduced smoking ) , particularly in subjects who did not intend to reduce or stop before admission . The level of satisfaction with the service and information relating to smoking cessation was also significantly higher in the treatment group . Subjects described the approach of the nurse and a leaflet devised for the study , as the most helpful aspects of the programme . The study highlights how the nurse , using appropriate theory to underpin such a programme , can facilitate smokers ' intention to stop or reduce tobacco consumption prior to hospital admission , and help them to prepare for their surgery , anaesthesia , and the hospital 's no smoking policy BACKGROUND Although many women quit smoking during pregnancy , the majority resume smoking shortly after giving birth . OBJECTIVES To test a program to prevent smoking relapse in the postpartum period by comparing the rates of continuous smoking abstinence , daily smoking , and smoking cessation self-efficacy in treatment and control groups . METHODS In a r and omized clinical trial , nurses provided face-to-face , in-hospital counseling sessions at birth , followed by telephone counseling . The target population included women who quit smoking during pregnancy and who gave birth at one of five hospitals . The 254 participating women were interviewed 6 months after delivery and assessed biochemically to determine smoking status . RESULTS The 6-month continuous smoking abstinence rate was 38 % in the treatment group and 27 % in the control group ( odds ratio [ OR ] = 1.63 , 95 % confidence interval [ CI ] .96 - 2.78 ) . Significantly more control ( 48 % ) than treatment ( 34 % ) group participants reported smoking daily ( OR = 1.80 , 95 % CI = 1.08 - 2.99 ) . Smoking cessation self-efficacy did not vary significantly between the groups . CONCLUSIONS Smoking cessation interventions focusing on the prenatal period have failed to achieve long-term abstinence . Interventions can be strengthened if they are extended into the postpartum period AIM To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model ( TTM ) compared to st and ard self-help smoking cessation literature . DESIGN R and omized controlled trial . SETTING Sixty-five West Midl and s general practice s. PARTICIPANTS R and omly sample d patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed . INTERVENTIONS Responders were r and omized to one of four interventions . The control group received st and ard self-help literature . In the Manual intervention group , participants received the Pro-Change system , a self-help workbook and three question naires at 3-monthly intervals , which generated individually tailored feedback . In the Phone intervention group , participants received the Manual intervention plus three telephone calls . In the Nurse intervention group , participants received the Manual intervention plus three visits to the practice nurse . MEASUREMENTS Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence , 12 months after study commencement . FINDINGS A total of 9.1 % of registered current smokers participated , of whom 83.0 % were not ready to quit . Less than half of participants returned question naires to generate second and third individualized feedback . Telephone calls reached 75 % of those scheduled , but few participants visited the nurse . There were small differences between the three Pro-Change arms . The odds ratio ( 95 % confidence intervals ) for all Pro-Change arms combined versus the control arm were 1.50 ( 0.85 - 2.67 ) and 1.53 ( 0.76 - 3.10 ) , for point prevalence and 6-month abstinence , respectively . This constitutes 2.1 % of the TTM group versus 1.4 % of the control group achieving confirmed 6-month sustained abstinence . CONCLUSIONS There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small 1 . We assessed whether a lifestyle modification programme implemented by nurse counsellors in a general practice setting would improve blood pressure ( BP ) control in treated hypertensive patients This study examined the effectiveness of a nurse-managed minimal-contact smoking cessation intervention for patients hospitalized for cardiac disease . A pre-test-post-test quasi-experimental design was used . Patients who smoked prior to admission to cardiac wards of five hospitals ( n = 388 ) received the intervention , whereas smoking patients in six other hospitals were given usual care ( n = 401 ) . The intervention was initiated at the hospital and continued after discharge . The core elements were stop-smoking advice from the cardiologist , a short bedside consultation with a nurse , administration of self-help material s and aftercare by the cardiologist . Smoking cessation was assessed after 3 months by self-report . Logistic regression analysis excluding dropouts , controlling for covariates including baseline differences showed significant intervention effects ( one-tailed significance test ) on point prevalence abstinence ( OR = 2.11 ) and continuous abstinence ( OR = 1.41 ) . Intention-to-treat analysis including dropouts as smokers showed a significant effect on point prevalence abstinence ( OR 1.35 ) . We conclude that , compared to usual care , the low-intensity smoking cessation intervention for cardiac in patients was more effective in achieving smoking cessation . However , the small effects and the process evaluation suggest that improvements are needed OBJECTIVE The aim of this study was to evaluate the effect of a smoking cessation intervention provided after discharge from a specialized cardiac hospital . DESIGN A r and omized pilot study ( N = 40 ) ; after discharge , the experimental group ( EG ) received 6 phone calls from a nurse specialized in tobacco cessation counselling . RESULTS Patients in the EG showed improved scores on two aspects of illness representations ( perceive their illness as chronic and reported less negative emotional representations ) . No significant difference in smoking cessation was observed at 6 months ( p = 0.72 ) . CONCLUSION The non-significant difference may be explained in part by the smoking characteristics within this sample exemplifying the more nicotine dependent " hard core " smokers who persist in their smoking habits despite the serious health consequences incurred by continued smoking . This population of smokers may require a more intensive , specialized intervention to achieve smoking cessation PURPOSE Smoking cessation is an important goal for smokers with coronary artery disease ( CAD ) because it reduces cardiac morbidity and mortality . Effective interventions for cigarette smokers with CAD exist , but they often are considered to be intensive and expensive . Stepped-care interventions have been proposed as a promising way to allocate smoking cessation treatments in a cost-effective manner . Stepped care refers to the practice of initiating treatment with low-intensity intervention and then exposing treatment failures to successively more intense interventions . METHODS To address the efficacy of this approach , 254 cigarette smokers hospitalized with CAD were provided a brief cessation intervention . The participants then were assigned r and omly to either a more intensive stepped-care treatment ( counseling and nicotine patch therapy ) or no additional treatment . Outcomes were point-prevalent abstinence measured 3 months and 1 year after hospital discharge . RESULTS Stepped-care treatment increased smoking cessation rates from 42 % to 53 % during a 3-month follow-up period ( P = .05 ) , but showed little effect at the 1-year follow-up assessment , as evidence d by a cessation rate for the minimal intervention group of 36 % versus 39 % for the stepped-care group ( P = .36 ) . CONCLUSIONS A stepped-care approach to smoking cessation increased short-but not long-term point-prevalent abstinence in patients with CAD . For improvement of long-term effectiveness , refinement of the timing and content of stepped-care interventions needs to occur OBJECTIVE To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients . RESEARCH DESIGN AND METHODS This r and omized controlled clinical trial involved 280 diabetic smokers ( age range 17 - 84 years ) who were r and omized either into control ( n = 133 ) or intervention ( n = 147 ) groups at 12 primary care centers and 2 hospitals located in Navarre , Spain . The intervention consisted of a 40-min nurse visit that included counseling , education , and contracting information ( a negotiated cessation date ) . The follow-up consisted of telephone calls , letters , and visits . The control group received the usual care for diabetic smokers . Baseline and 6-month follow-up measurements included smoking status ( self-reported cessation was verified by urine cotinine concentrations ) , mean number of cigarettes smoked per day , and stage of change . RESULTS At the 6-month follow-up , the smoking cessation incidence was 17.0 % in the intervention group compared with 2.3 % in the usual care group , which was a 14.7 % difference ( 95 % CI 8.2 - 21.3 % ) . Among participants who continued smoking , a significant reduction was evident in the average cigarette consumption at the 6-month follow-up . The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group ( P < 0.01 ) . CONCLUSIONS A structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients BACKGROUND Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease ( COPD ) . SETTING A Regional Respiratory Centre ( RRC ) out-patient department in Northern Irel and . METHODS A r and omised controlled trial ( RCT ) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses . Smoking status was biochemically vali date d and stage of change , nicotine addiction and dyspnoea were recorded at 2 , 3 , 6 , 9 and 12 months . PARTICIPANTS Ninety-one cigarette smokers with COPD were enrolled in the study ( mean age 61 years , 47 female ) . RESULTS After 12 months cessation rates were not significantly different between groups ( p=0.7 ) , but all groups had a significant reduction in their nicotine addiction ( p=0.03 - 0.006 ) . No changes in subjects ' motivation or dyspnoea were detected over the 12 months . CONCLUSION Patients with COPD were unable to stop smoking regardless of the type of support they received . Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena BACKGROUND Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients . This r and omized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California . METHODS Patients were r and omly assigned to usual care ( n = 990 ) , nurse-mediated , behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact ( minimal intervention , n = 473 ) , or the same inpatient counseling with 4 postdischarge telephone contacts ( intensive intervention , n = 561 ) . The main outcome measure , smoking cessation rate , was corroborated by plasma cotinine determination or family confirmation , 1 year after enrollment . RESULTS At 1 year smoking cessation rates were 27 % , 22 % , and 20 % for intensive intervention , minimal intervention , and usual care groups , respectively ( P = .009 for intensive vs usual care ) . Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care ( odds ratios , 1.6 and 2.0 , respectively ) . CONCLUSIONS A multicomponent smoking cessation program consisting of physician advice ; in-hospital , nurse-mediated counseling ; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers . Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans BACKGROUND This study evaluated the effectiveness of three smoking cessation interventions for this population : ( 1 ) modified usual care ( UC ) ; ( 2 ) brief advice ( A ) ; and ( 3 ) brief advice plus more extended counseling during and after hospitalization ( A + C ) . METHODS Smokers ( 2,095 ) who were in- patients in four hospitals were r and omly assigned to condition . Smoking status was ascertained via phone interview 7 days and 12 months post-discharge . At 12 months , reports of abstinence were vali date d by analysis of saliva cotinine . Intent to treat analyses were performed . RESULTS At 7-day follow-up , 24.2 % of participants reported abstinence in the previous 7 days . There were no differences between conditions . At 12-month follow-up , self-reported abstinence was significantly higher in the A + C condition ( UC ( 15.0 % ) vs. A ( 15.2 % ) vs. A + C ( 19.8 % ) ) . There was no significant difference among conditions in cotinine-vali date d abstinence , however ( UC ( 8.8 % ) vs. A ( 10.0 % ) vs. A + C ( 9.9 % ) ) . CONCLUSIONS These interventions for hospital in- patients did not increase abstinence rates . Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria , the fact that pharmacological aids were not provided , and a stage-matching approach that result ed in less intensive counseling for participants unwilling to set a quit date Strict implementation of guidelines directed at multiple targets reduces vascular risk in diabetic patients . Whether this also applies to patients with chronic kidney disease ( CKD ) is uncertain . To evaluate this , the MASTERPLAN Study r and omized 788 patients with CKD ( estimated GFR 20 - 70 ml/min ) to receive additional intensive nurse practitioner support ( the intervention group ) or nephrologist care ( the control group ) . The primary end point was a composite of myocardial infa rct ion , stroke , or cardiovascular death . During a mean follow-up of 4.62 years , modest but significant decreases were found for blood pressure , LDL cholesterol , anemia , proteinuria along with the increased use of active vitamin D or analogs , aspirin and statins in the intervention group compared to the controls . No differences were found in the rate of smoking cessation , weight reduction , sodium excretion , physical activity , or glycemic control . Intensive control did not reduce the rate of the composite end point ( 21.3/1000 person-years in the intervention group compared to 23.8/1000 person-years in the controls ( hazard ratio 0.90 ) ) . No differences were found in the secondary outcomes of vascular interventions , all-cause mortality or end-stage renal disease . Thus , the addition of intensive support by nurse practitioner care in patients with CKD improved some risk factor levels , but did not significantly reduce the rate of the primary or secondary end points Background —Although men hospitalized with cardiovascular disease ( CVD ) show high smoking-cessation rates , similar data for women are lacking . We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD . Methods and Results —In this r and omized controlled trial conducted from 1996 to 2001 , 277 women diagnosed with CVD ( mean age 61±10 years ) were r and omly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group ( UG ; n=135 ) or intervention group ( IG ; n=142 ) . Baseline histories were obtained , and interviews to ascertain self-reported smoking status occurred at 6 , 12 , 24 , and 30 months after hospitalization . The UG received strong physician ’s advice , a self-help pamphlet , and a list of community re sources . The IG received strong physician ’s advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside , with telephone contact at intervals after discharge . The groups were similar demographically and had smoked cigarettes for a median of 38 ( IG ) or 40 ( UG ) years . Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis , and risk differences between groups were determined . Time smoke-free was significantly greater for the IG than the UG ( P = 0.038 ) . Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG ( P > 0.15 at all times ) . Conclusions —Cognitive behavioral intervention result ed in longer average times to resumption of smoking , but in these 2 groups of older women with limited social and financial re sources , long-term success rates were similar . Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time INTRODUCTION Many stroke survivors would benefit from modification of their lifestyle in order to reduce their risk of recurrent stroke . We investigated if tailored smoking cessation advice would yield a higher smoking cessation rate and a higher rate with sustained abstinence in ex-smokers in the intervention group than among controls . MATERIAL AND METHODS Patients admitted with an acute stroke or a transient ischaemic attack were included in a r and omised controlled trial focusing on control of lifestyle risk factors and hypertension . Here , we report the intervention focused on smoking cessation . We used multiple logistic regression analysis to identify patient characteristics associated with smoking cessation . Analyses were by intention to treat excluding those who died or suffered severe disease . RESULTS We included 254 patients with a history of smoking . Two years after inclusion , 15 of 57 ( 26 % ) baseline smokers in the intervention group had stopped smoking versus eight of 56 ( 14 % ) among controls ( p = 0.112 ) . Living with a partner ( p = 0.012 ) , having at least ten years of education ( p = 0.012 ) , and not being exposed to smoking at home ( p = 0.036 ) were independent predictors of smoking cessation . CONCLUSION We did not achieve our aim of higher smoking cessation rates in the intervention group . Future smoking cessation interventions should be more intensive , focus on patients ' social circumstances and , if possible , involve patients ' relatives . FUNDING This study was supported by the Ludvig and Sara Elsass Foundation , the Lundbeck Foundation and The Danish Heart Foundation ( Grant 07 - 4-B703-A1378 - 22384F ) . TRIAL REGISTRATION This protocol is registered with Clinical Trials.gov ( NCT 00253097 ) Disease diagnosis and poor quality of life has been suggested as a “ teachable moment ” that facilitates smoking cessation , yet many patients continue to smoke . One reason for this inconsistency may be the potential moderating role of depressed mood . This study prospect ively examined the role of depressed mood on the relationship between physical quality of life ( PQoL ) and smoking cessation among medically ill smokers . We hypothesized that poorer PQoL will be associated with smoking cessation , but only among those with little to no depressed mood . Nurses delivered smoking cessation counseling to medically ill patients ( N = 273 ) who continued to smoke despite past hospitalization . Participants were assessed at baseline and at 2 , 6 , and 12-months later . The interaction between PQoL and depressed mood significantly predicted 1 ) 7-day point prevalence abstinence rates at both 2 and 12 months post-treatment [ 2 months : adjusted OR = 1.005 , 95%CI 1.001–1.009 , p < .05 ; 12 months : adjusted OR = 1.007 , 95%CI 1.002–1.011 , p < .005 ) ] and 2 ) continuous abstinence rates at both 2 and 12 months post-treatment [ 2 months : adjusted OR = 1.011 , 95%CI 1.004–1.019 , p < .005 ; 12 months : adjusted OR = 1.006 , 95%CI 1.001–1.011 , p < .05 ] even after controlling for important covariates . The odds of quitting smoking increased for every one-unit decrease in PQoL , but only among those with little to no depressed mood . Medically ill smokers with poor quality of life may need more intensive smoking cessation interventions that include mood management to help them quit smoking Objective : Does the provision of a nurse‐based intervention lead to smoking cessation in hospital patients OBJECTIVE The purpose of this study was to assess the use of nicotine replacement therapy ( NRT ) in a nurse-managed smoking cessation program . DESIGN A cohort design nested within the WINS r and omized clinical trial was used with follow-up at 2 , 7 , 21 , 28 , and 90 days . SETTING The study took place in 10 hospitals in the San Francisco Bay Area . SUBJECTS Participants included 142 women hospitalized with cardiovascular disease ( CVD ) . OUTCOME MEASURE The outcome measure was the use of NRT after having been assessed as eligible for its use . INTERVENTION NRT was used as an adjunct in the behavioral intervention protocol . NRT was recommended during the hospital intervention and during the 90-day outpatient phase . RESULTS Of 142 women in the intervention group , 127 met the criteria for NRT use . During the 5 follow-up assessment s , the reported NRT use ranged from 9 % to 22 % . CONCLUSION A low NRT use rate among women with CVD is evident . The results suggest that future research about NRT myths pertaining to women is needed . Nurses can help patients dispel these myths and prevent smoking relapse in women with CVD OBJECTIVES This r and omized controlled trial assessed the efficacy of a smoking relapse prevention program featuring 3 postdischarge telephone contacts with subjects who had quit smoking on hospitalization . METHODS Patients were r and omly assigned to public health nurse-mediated behaviorally oriented in-patient counseling focused on relapse prevention ( control group , n = 49 ) , or the same inpatient counseling with postdischarge telephone contacts at 7 , 21 and 42 days after discharge ( intervention group , n = 57 ) . The main outcome measure , smoking cessation rate , was obtained from self-reports at 3 , 6 and 12 months after discharge . Smoking cessation at 12 months after discharge was confirmed by urinary nicotine concentration . RESULTS At 3 , 6 and 12 months smoking cessation rates were 83 % , 63 % and 56 % for the intervention group , and 76 % , 65 % and 51 % for control group . After adjustment for sex , age , having any complication , number of family members , smoking status on admission , strength of nicotine dependence and self confidence to quit smoking , the odds ratio of cessation among the intervention group were 1.46 ( 95 % confidence interval ( CI ) : 0.48 - 4.47 ) , 0.82 ( 95 % CI : 0.31 - 2.17 ) and 0.99 ( 95 % CI : 0.40 - 2.45 ) at 3 , 6 and 12 months after discharge , respectively . CONCLUSION This program had limited efficacy to maintain postdischarge smoking abstinence . We should re-consider the modality of smoking cessation program for relapse prevention among hospitalized patients Background : Preventive guidelines on cardiovascular risk management recommend lifestyle changes . Support for lifestyle changes may be a useful task for practice nurses , but the effect of such interventions in primary prevention is not clear . We examined the effect of involving patients in nurse-led cardiovascular risk management on lifestyle adherence and cardiovascular risk . Methods : We performed a cluster r and omized controlled trial in 25 practice s that included 615 patients . The intervention consisted of nurse-led cardiovascular risk management , including risk assessment , risk communication , a decision aid and adapted motivational interviewing . The control group received a minimal nurse-led intervention . The self-reported outcome measures at one year were smoking , alcohol use , diet and physical activity . Nurses assessed 10-year cardiovascular mortality risk after one year . Results : There were no significant differences between the intervention groups . The effect of the intervention on the consumption of vegetables and physical activity was small , and some differences were only significant for subgroups . The effects of the intervention on the intake of fat , fruit and alcohol and smoking were not significant . We found no effect between the groups for cardiovascular 10-year risk . Interpretation : Nurse-led risk communication , use of a decision aid and adapted motivational interviewing did not lead to relevant differences between the groups in terms of lifestyle changes or cardiovascular risk , despite significant within-group differences OBJECTIVE : To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infa rct ion patients aged 50 - 70 years . DESIGN : Habitual physical activity , food habits , and smoking habits were assessed from question naires at admission to hospital and at the one year follow up . Initially , all patients were invited to join an exercise programme and were informed about cardiovascular risk factors . Four weeks after discharge from the hospital , 87 patients were r and omised to follow up at the coronary prevention unit by a special trained nurse ( the intervention group ) , and 81 to follow up by their general practitioners ( the usual care group ) . After r and omisation , the intervention group was educated about the effects of smoking cessation , dietary management , and regular physical activity . The intervention group also participated in a physical training programme two to three times weekly for 10 - 12 weeks . MAIN RESULTS : 89 % of the patients referred to the intervention group improved their food habits compared with 62 % of the patients referred to the usual care group ( P = 0.008 ) . Furthermore , 50 % of the smokers referred to the intervention group stopped smoking compared to 29 % in the usual care group ( P = 0.09 ) . Changes in physical activity did not differ between the groups . CONCLUSIONS : This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infa rct ion . Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results . The exercise programme had no advantage in supporting physical activity compared to usual care Smoking cessation counseling is an important element of tobacco control in the workplace , but it is not easy to persuade workers to stop smoking . We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al. , which consisted of one brief individual counseling session and 4 follow-up telephone calls . Two hundred and twenty-eight smokers who visited our center for an annual health checkup were r and omly divided into two group : 117 were assigned to the intervention group , and 111 were controls . Smoking status question naires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session . Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program . During the counseling session , carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking . Only those clients who set a quit date during their counseling sessions received follow-up telephone calls . It was easy to implement this program ( 15 to 20 minutes long ) during a health checkup . No significant differences were observed in the baseline characteristics of the two groups . The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group . The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group . In the intervention group , the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success , but other baseline characteristics were similar in those who quit smoking and those who did not . The effectiveness and easy applicability of this cessation program was proved in the present study . Further examinations in various setting s are expected to clarify the effectiveness of this program BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease Background Smoking cessation is probably the most important single action after a coronary event . In order to increase the effectiveness of smoking cessation programs , it is important to have knowledge of the predictors of smoking cessation . Further , it is unknown whether smoking cessation programs have impact on these predictors . Methods Data were obtained from a r and omized controlled trial of smoking cessation intervention in 240 smokers aged less than 76 years admitted for myocardial infa rct ion , unstable angina , or cardiac bypass surgery . Baseline characteristics were prospect ively recorded . Smoking cessation was determined by self report and biochemical verification at 12 months follow-up . Results In multivariate logistic regression analysis , a high level of nicotine addiction , low level of self-confidence in quitting and having previous coronary heart disease were significant negative predictors of smoking cessation at 12 months follow-up . Having previous coronary heart disease and a diagnosis other than acute myocardial infa rct ion as a reason for admission were important negative predictors of abstinence in the usual care group , in contrast to the intervention group , although this did not reach a level of significance in the subgroup interaction analyses . A high level of nicotine addiction was a strong negative predictor in both groups . Conclusion A high level of nicotine addiction is an important negative predictor of smoking cessation , even within an individualized smoking cessation program . Smoking cessation intervention seems to be especially effective in patients with previous coronary heart disease and in patients with unstable angina or coronary artery bypass surgery , compared to usual care The purpose of this study was to evaluate the effect of a nurse-directed smoking cessation intervention for adults hospitalized in a small community hospital using a quasiexperimental , prospect i ve , longitudinal design with biochemical validation of self-reported tobacco abstinence . Sixty-eight in patients were assigned to either a control ( n = 30 ) or an intervention group ( n = 38 ) . The control group received smoking cessation literature . The intervention group received smoking cessation literature and a nursing intervention . Each member of the intervention group was r and omly assigned to a one or four telephone call subgroup for post discharge nurse follow-up at 3 months . Fifty-five participants completed the study . Smokers receiving the nurse-directed intervention were significantly more likely to be tobacco abstinent at 3 months ( n = 17 , 55 % ) than smokers in the control group ( n = 5 , 21 % ) . Within the intervention group , tobacco abstinence at 3 months was not significantly different between the one and four telephone call groups . For the total sample , smoking relapse was significantly higher for participants who lived with another smoker BACKGROUND Smoking cessation is widely recommended for secondary stroke prevention . However , little is known about the efficacy of smoking cessation intervention after stroke or transient ischemic attack ( TIA ) . METHODS Ninety-four smokers under age 76 , admitted with ischemic stroke or TIA were r and omized to minimal smoking cessation intervention or intensive smoking cessation intervention . All patients attended a 30-min individual counseling by the study nurse . Patients r and omized to intensive smoking cessation intervention also participated in a 5-session outpatient smoking cessation program by an authorized smoking cessation instructor , a 30-min outpatient visit after 6 weeks , and 5 telephone counseling sessions by the study nurse . Free sample s of nicotine replacement therapy were offered as part of the intensive smoking cessation program . Smoking cessation rates at 6 months were determined by self-report and verified by measurement of exhaled carbon monoxide ( CO ) . Fewer patients than expected were recruited , which renders this report a pilot study . RESULTS The 6-month self-reported smoking cessation rate was 37.8 % in the minimal intervention group and 42.9 % in the intensive intervention group . Smoking cessation rates verified by exhaled CO levels in the minimal intervention group and the intensive intervention group were 28.9 % and 32.7 % , respectively . No difference was found between the two groups ( χ(2 ) = 0.16 , p = .69 ) . CONCLUSIONS Overall smoking cessation rates were moderate and comparable to the results from other studies . Intensive smoking cessation intervention was not superior to short smoking cessation intervention . Thus , other factors than intensity of smoking cessation intervention might influence the smoking cessation rates after stroke or TIA This study examined the long-term effectiveness of a postpartum smoking relapse prevention intervention by evaluating the smoking status and smoking cessation self-efficacy of original study participants at 12 months following delivery . Two hundred and thirty-eight women who had participated in a r and omized clinical trial , a nurse-delivered relapse prevention intervention , were visited in their homes . Data were collected on smoking status , self-efficacy , mental health , alcohol use , breast feeding , social support , smoking in the social environment , and sociodemographics . Smoking status was verified with measures of carbon monoxide in expired air . The 12-month continuous smoking abstinence rate was 21.0 % in the treatment group and 18.5 % in the control group ; odds ratio ( OR ) = 1.17 , 95 % confidence interval ( CI ) = 0.62 - 2.22 . One half ( 50.4 % ) of the control group and 41.2 % of the treatment group reported smoking daily at 12 months ; OR = 1.45 , 95 % CI = 0.87 - 2.43 . The treatment group attained higher self-efficacy . Four variables were associated with relapse to daily smoking ; breast feeding and mental health had protective effects , while partners who smoked and greater amount smoked prior to pregnancy had adverse effects OBJECTIVES In France , hospitals have been smoke free since February 2007 . A period of hospitalization may be a good time to enhance a smoker 's motivation to quit . This study aim ed to assess whether training medical staff in smoking cessation management might improve the rate of smoking cessation during hospitalization . STUDY DESIGN Non-r and omized intervention study . METHODS Staff of the participating care units either received ( intervention group ) or did not receive ( control group ) training in smoking cessation management . The dependent variable was the proportion of in patients that continued to smoke before ( Period 1 ) and after ( Period 2 ) the training session . RESULTS In total , 358 patients were included . In Period 1 , 55.6 % and 50 % of the smokers from the intervention and control groups stopped smoking , respectively ; the corresponding rates in Period 2 were 64.3 % and 48.1 % . In Period 2 , 36.4 % and 31.8 % of the smokers from the intervention and control groups cl aim ed that they had received motivational counselling . In the intervention group , the request rate for nicotine replacement therapy ( NRT ) was higher ( 41.7 % ) compared with the control group ( 11.1 % ) . In both groups , patients asked for NRT more often ( P < 0.001 ) when they had received motivational counselling . CONCLUSIONS This study was not able to demonstrate that training medical staff in smoking cessation management has a significant impact on smoking cessation in hospitalized smokers . The delivery of medium-intensity support to all smokers appears to be out of reach of physician/nurse teams . New strategies are needed , including a team specifically dedicated to the problems of addiction PURPOSE / OBJECTIVES To determine the effectiveness of a nurse-managed minimal smoking-cessation intervention among hospitalized patients with cancer . DESIGN Prospect i ve , two-group , r and omized clinical trial . SETTING Urban , academic , tertiary-care setting . SAMPLE 28 adult male and female smokers with a diagnosis of cancer who are hospitalized for a surgical procedure . METHODS During hospitalization , subjects were assigned to a minimal smoking-cessation intervention group ( n = 14 ) or a usual care group ( n = 14 ) . Verification of smoking status was performed at a clinic visit six weeks postintervention . Nonsmoking status was defined as self-report of zero cigarettes/day during the prior week and confirmed by saliva cotinine analysis . MAIN RESEARCH VARIABLES One-time , Inpatient , nurse-managed , minimal smoking-cessation intervention , self-reported smoking status , and saliva cotinine level of < or = 14 ng/ml . FINDINGS Upon hospital admission , 64 % of the intervention group and 71 % of the usual care group reported their intention to quit smoking . At six weeks postintervention , only 21 % and 14 % of the intervention and usual care group , respectively , were classified as abstinent from smoking . More than 90 % of the intervention group members who resumed smoking did so within first week of discharge . IMPLICATION S FOR NURSING PRACTICE A more intensive intervention may be necessary to assist hospitalized surgical patients in achieving smoking cessation . Additional contact prior to discharge or within the first few days postdischarge may be necessary to reinforce strategies for remaining abstinent In a trial to evaluate the effectiveness of a nurse-directed intervention design ed to help patients decrease dietary intake of fat , quit or decrease smoking , and increase exercise , 138 women who underwent coronary artery bypass surgery were r and omized to receive special intervention ( SI ) or usual care ( UC ) . The SI group received a behavioral program based on self-efficacy theory in the home 2 weeks after discharge with regular follow-up . The UC group received routine medical care . Risk factors and lifestyle behaviors were measured at baseline and 1 year after surgery in 116 ( 84 % ) women ( SI = 59 , UC = 57 ) . The SI group decreased their total fat intake from a mean of 38 % of calories at baseline to 35 % at 1 year , while the UC group increased it from 36 % to 38 % . The prevalence of smoking decreased from 24 % at baseline to 8 % at 1 year in the SI group and from 19 % to 14 % in the UC group . At follow-up , the quit rate in those smoking at baseline was 64 % in the SI group , with no new smokers , and 55 % in the UC group , with three new smokers . Both groups reported improvement in exercise , with the proportion of women reporting participation in some form of regular exercise slightly higher in the SI group than in the UC group , 54 % and 51 % , respectively AIMS An earlier combined proactive and reactive telephone follow-up intervention for acute myocardial infa rct ion patients after discharge from hospital showed positive effects after six months . The aim of the present study was to assess whether the intervention has long-term effects up to 18 months after discharge . DESIGN A prospect i ve r and omised controlled trial with 18 months follow-up . METHOD The trial was conducted with 288 patients allocated to a telephone follow-up intervention group ( n = 156 ) or control group ( n = 132 ) . The primary endpoint was health-related quality of life using the SF-36 . Secondary endpoints included smoking and exercise habits , return to work and rehospitalisation due to chest pain . RESULTS There were significant improvements over time on most dimensions of health-related quality of life in both the intervention and control group to US norm population levels on most SF-36 dimensions and summary scores . The intervention group showed no overall significant improvement beyond six months in the physical or mental summary scores , but there was a significant effect for those aged 70 or above . Although there was a promising effect for rehospitalisation due to chest pain , no significant differences were found between the groups on the secondary endpoints after six months . CONCLUSION This study demonstrated that despite positive short-term effects at six months , the telephone follow-up intervention had no long-term effects on health-related quality of life or secondary endpoints . However , the potential for improvement beyond six months was less than anticipated reflecting a reduced morbidity among acute myocardial infa rct ion patients . RELEVANCE TO CLINICAL PRACTICE Telephone follow-up after discharge from hospital is an easy implementable follow-up intervention enabling individualised provision of information and support in a time often experienced as stressful by patients . Our study indicates that six months is an adequate support period . Despite positive results six months after discharge no significant added long-term effects of telephone follow-up , compared to usual care were found in this study BACKGROUND Hospitalization may be an opportune time to change smoking behavior because it requires smokers to abstain from tobacco at the same time that illness can motivate them to quit . A hospital-based intervention may promote smoking cessation after discharge . METHODS We tested the efficacy of a brief bedside smoking counseling program in a r and omized controlled trial at Massachusetts General Hospital , Boston . The 650 adult smokers admitted to the medical and surgical services were r and omly assigned to receive usual care or a hospital-based smoking intervention consisting of ( 1 ) a 15-minute bedside counseling session , ( 2 ) written self-help material , ( 3 ) a chart prompt reminding physicians to advise smoking cessation , and ( 4 ) up to 3 weekly counseling telephone calls after discharge . Smoking status was assessed 1 and 6 months after hospital discharge by self-report and vali date d at 6 months by measurement of saliva cotinine levels . RESULTS One month after discharge , more intervention than control patients were not smoking ( 28.9 % vs 18.9 % ; P=.003 ) . The effect persisted after multiple logistic regression analyses adjusted for baseline group differences , length of stay , postdischarge smoking treatment , and hospital readmission ( adjusted odds ratio , 2.19 ; 95 % confidence interval , 1.34 - 3.57 ) . At 6 months , the intervention and control groups did not differ in smoking cessation rate by self-report ( 17.3 % vs 14.0 % ; P=.26 ) or biochemical validation ( 8.1 % vs 8.7 % ; P=.72 ) , although the program appeared to be effective among the 167 patients who had not previously tried to quit smoking ( 15.3 % vs 3.7 % ; P=.01 ) . CONCLUSIONS A low-intensity , hospital-based smoking cessation program increased smoking cessation rates for 1 month after discharge but did not lead to long-term tobacco abstinence . A longer period of telephone contact after discharge might build on this initial success to produce permanent smoking cessation among hospitalized smokers AIM To evaluate the effectiveness in primary care of a stepped smoking cessation intervention based on the transtheoretical model of change . DESIGN Cluster r and omized trial ; unit of r and omization : basic care unit ( family physician and nurse who care for the same group of patients ) ; and intention-to-treat analysis . SETTING All interested basic care units ( n = 176 ) that worked in 82 primary care centres belonging to the Spanish Preventive Services and Health Promotion Research Network in 13 regions of Spain . PARTICIPANTS A total of 2,827 smokers ( aged 14 - 85 years ) who consulted a primary care centre for any reason , provided written informed consent and had valid interviews . MEASUREMENTS The outcome variable was the 1-year continuous abstinence rate at the 2-year follow-up . The main variable was the study group ( intervention/control ) . Intervention involved 6-month implementation of recommendations from a Clinical Practice Guideline which included brief motivational interviews for smokers at the precontemplation-contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help and reinforcing intervention in the maintenance stage . Control group involved usual care . Among others , characteristics of tobacco use and motivation to quit variables were also collected . FINDINGS The 1-year continuous abstinence rate at the 2-year follow-up was 8.1 % in the intervention group and 5.8 % in the control group ( P = 0.014 ) . In the multivariate logistic regression , the odds of quitting of the intervention versus control group was 1.50 ( 95 % confidence interval = 1.05 - 2.14 ) . CONCLUSIONS A stepped smoking cessation intervention based on the transtheoretical model significantly increased smoking abstinence at a 2-year follow-up among smokers visiting primary care centres BACKGROUND Chronic kidney disease ( CKD ) is associated with increased cardiovascular risk . Here we evaluate whether strict implementation of guidelines aim ed at multiple targets with the aid of nurse practitioners ( NP ) improves management in patients with CKD . METHODS MASTER PLAN is a r and omised controlled clinical trial , performed in nine Dutch hospitals . Patients with CKD ( estimated glomerular filtration rate ( eGFR ) 20 - 70 ml÷min ) were r and omised to receive NP support ( intervention group ( IG ) ) or physician care ( control group ( CG ) ) . Patients were followed for a median of five years . Presented data are an interim analysis on risk factor control at two-year follow-up . RESULTS We included 788 patients ( 532 M , 256 F ) , ( 393 CG , 395 IG ) , mean ( ±SD ) age 59 ( ±13 ) years , eGFR 38 ( ±15 ) ml÷min÷1.73m(2 ) , blood pressure ( BP ) 138 (±21)÷80 ( ±11 ) mmHg . At two years 698 patients ( 352 IG , 346 CG ) could be analysed . IG as compared with CG had lower systolic ( 133 vs 135 mmHg ; p= 0.04 ) and diastolic BP ( 77 vs 80 mmHg ; p=0.007 ) , LDL cholesterol ( 2.30 vs 2.45 mmol(-l ) ; p= 0.03 ) , and increased use of ACE inhibitors , statins , aspirin and vitamin D. The intervention had no effect on smoking cessation , body weight , physical activity or sodium excretion . CONCLUSION In both groups , risk factor management improved . However , changes in BP control , lipid management and medication use were more pronounced in IG than in CG . Lifestyle interventions were not effective . Coaching by NPs thus benefits everyday care of CKD patients . Whether these changes translate into improvement in clinical endpoints remains to be established This study aim ed to evaluate the effect of a motivational , minimal intervention approach to smoking cessation in an open , r and omized design conducted by nurses as routine work in a lung clinic . Subjects who smoked less than 10 cigarettes x day(-1 ) , and subjects who smoked > or = 10 cigarettes x day(-1 ) and who had refused to participate in a smoking cessation trial with nicotine replacement therapy , were r and omly allocated to a motivational approach to smoking cessation or to a control group . The motivational approach consisted of a nurse-conducted 5 min consultation concerning reasons to quit smoking , brochures about smoking cessation and advice about how to quit . After 4 - 6 weeks , subjects in the motivational group received a letter encouraging them to quit smoking . After 1 year , all subjects were contacted by phone and smoking status reported . Subjects cl aim ing to be abstinent attended the clinic for carbon monoxide verification . A total of 507 subjects were enrolled , 254 in the motivational group and 253 in the control group . The mean age of the motivational group was 51 yrs , 50 % were males and they smoked a mean of 13 cigarettes x day(-1 ) . The mean age of the control group was 53 yrs , 61 % were males and they smoked a mean of 12 cigarettes x day(-1 ) . At the 1 year follow-up , the success rate for point prevalence ( no smoking at 1 year and during the preceding month ) was 8 , 7 % in the motivational group versus 3.6 % in the control group ( p=0.025 ) . The 12 months sustained success rate ( no smoking at all during the year ) was 3.1 versus 1.2 % ( p=0.22 ) . The point prevalence for light smokers ( < 10 cigarettes x day(-1 ) ) was 13.9 % in the motivational group versus 6.3 % in control group ( p=0.12 ) , and for heavy smokers ( 10 or more cigarettes x day(-1 ) ) 5.2 % versus 1.9 % ( p=0.20 ) . In conclusion , the effect of this nurse-conducted , minimal intervention , motivational approach seems promising as the quit rate at 1 year follow-up had doubled Smokers are often advised to quit in a discussion of future health risks . The authors tested whether adding information about personal effects of smoking would motivate hospital out patients to stop smoking more than advice about potential hazards would . Ninety smokers in a general screening clinic were r and omized to receive education alone or education plus an additional motivational intervention that contained immediate feedback about the smoker ’s exhaled carbon monoxide ( CO ) values , spirometry results , and pulmonary symptoms . A self-report of smoking status was obtained one , four , and 12 months after the intervention . In addition , at 12 months , exhaled CO measurements were made . Smokers who received the additional motivational intervention were more than twice as likely to report quitting some time during the 12-month follow-up ( 40 % vs. 16 % , p=0.015 ) . At 12 months , 33 % of the intervention group and 10 % of the control group smokers tested had achieved Co-vali date d cessation ( p=0.03 ) . Counting all patients not contacted as continuing to smoke , the percentages were 20 % vs. 7 % ( p=0.06 ) . These practical feedback methods to motivate cessation deserve testing in other setting The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease ( COPD ) increases the rate of smoking cessation . In total , 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and r and omly allocated to : confrontational counselling by a nurse with nortriptyline for smoking cessation ( experimental group ) ; regular counselling by a nurse with nortriptyline ( control group 1 ) ; or “ care as usual ” for smoking cessation by the general practitioner ( control group 2 ) . Only the experimental group was confronted with their abnormal spirometry ( mean forced expiratory volume in one second ( FEV1 ) post-bronchodilator 80.5 % predicted , mean FEV1/forced vital capacity post-bronchodilator 62.5 % ) . There was no difference in cotinine-vali date d prolonged abstinence rate between the experimental group ( 11.2 % ) and control group 1 ( 11.6 % ) from week 5–52 ( odds ratio ( OR ) 0.96 , 95 % confidence interval ( CI ) 0.43–2.18 ) . The abstinence rate was approximately twice as high in the experimental group compared with control group 2 ( 5.9 % ) , but this difference was not statistically significant ( OR 2.02 , 95 % CI 0.63–6.46 ) . The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry . The high failure rates ( ≥88 % ) highlight the need for treating tobacco addiction as a chronic relapsing disorder BACKGROUND Although office-based and telephone support services enhance the rate of smoking cessation in managed care systems , it is not clear whether such services are effective for very low-income smokers . We evaluated the comparative effectiveness of usual care ( physician-delivered advice and follow-up ) and usual care enhanced by 6 computer-assisted telephonic-counseling sessions by office nurses and telephone counselors for smoking cessation in very low-income smokers in Medicaid managed care . METHODS A r and omized clinical trial comparing the 2 approaches was conducted in 3 Michigan community health centers . All clinicians and center staff received st and ard training in usual care . Selected nurses and telephone counselors received special training in a computer-assisted counseling program focusing on relapse prevention . RESULTS The majority of the study population ( 233 adult smokers with telephones ) were white ( 64 % ) women ( 70 % ) with annual incomes of less than $ 10,000 ( 79 % ) and with prescriptions of nicotine replacement therapy ( > 90 % ) . At 3 months , quit rates ( smoke-free status verified by carbon monoxide monitors ) were 8.1 % in the usual-care group and 21 % in the telephonic-counseling group ( P=.009 ) by intention-to-treat analysis . Special tracking methods were successful in maintaining participants in treatment . CONCLUSIONS Smoking cessation rates are enhanced in a population of very low-income smokers if individualized telephonic-counseling is provided . State and Medicaid managed care plans should consider investing in both office-based nurse and central ized telephonic-counseling services for low-income smokers AIM The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu , China . BACKGROUND Epidemiological studies indicate a dose- , level- and duration -dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality . Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes . DESIGN METHODS A r and omized controlled trial was conducted . Coronary heart disease patients ( n = 167 ) who met the sampling criteria in two tertiary medical centres in Chengdu , south-west China , were r and omly assigned to either an intervention group ( the cardiac rehabilitation programme ) or control group ( the routine care ) . The change of health behaviours ( walking performance , step II diet adherence , medication adherence , smoking cessation ) and physiological risk parameters ( serum lipids , blood pressure , body weight ) were assessed to evaluate the programme effect . RESULTS Patients in the intervention group demonstrated a significantly better performance in walking , step II diet adherence , medication adherence ; a significantly greater reduction in serum lipids including triglyceride , total cholesterol , low-density lipoprotein ; and significantly better control of systolic and diastolic blood pressure at three months . The majority of these positive impacts were maintained at six months . The effect of the programme on smoking cessation , body weight , serum high-density lipoprotein , was not confirmed . CONCLUSIONS A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients . Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease . RELEVANCE TO CLINICAL PRACTICE This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients . Furthermore , the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care BACKGROUND PAS ( Personal Advice in Stopping smoking ) combines two of the most effective smoking cessation interventions : multiple computer tailoring and tailored counselling by a practice nurse in the general practice . METHODS / DESIGN Since May 2009 , practice nurses are recruiting smoking patients . Each practice nurse is asked to recruit 15 adult smokers who are willing to quit within 6months and have access to the Internet . Smokers can sign up for PAS through the PAS website and are then r and omized into one of three groups receiving multiple tailoring and counselling ( MTC ) , multiple tailoring ( MT ) or usual care ( UC ) , respectively . All groups receive question naires at baseline , 2days after a set quit date and at 6weeks , 6months and 12months follow-up . The MT group receives tailored , iterative feedback letters at the first four measurements points . At 12months follow-up biochemical validation will take place amongst respondents reporting to have quit . The three groups will be compared with regard to quit attempt rate , point prevalence abstinence and continued abstinence by means of logistic multilevel regression analyses . Linear multilevel regression analyses will be used to compare the three groups regarding smoking related beliefs . DISCUSSION The present paper provides an extensive description of the development of PAS and of the design of the study towards its effectiveness . This might provide insight into PAS ' potentially effective working mechanisms . The results concerning effectiveness may contribute to knowledge about the effectiveness of smoking cessation interventions aim ed at smoking adults . TRIAL REGISTRATION Dutch Trial Register NTR1351 Table . SI Units Systematic modification of coronary risk factors is not integrated into the medical care provided to most of the more than 1 million patients treated annually in the United States for acute myocardial infa rct ion by percutaneous transluminal coronary angioplasty or coronary artery surgery . Most of such patients have lipoprotein abnormalities [ 1 ] , and nearly one half smoke [ 2 ] . These risk factors , which contribute to subsequent morbidity and mortality , remain highly prevalent after acute cardiac events . Failure to integrate comprehensive risk factor modification into the st and ard medical care provided to patients after acute cardiac events primarily reflects the lack of an organizational framework or system . This deficiency in re source allocation for preventive and rehabilitative aspects of care in turn reflects the predominant orientation of the U.S. health care system to the management of acute illness [ 3 ] . Several clinical research studies have shown the effectiveness of risk factor modification , especially treatment of lipoprotein abnormalities [ 4 - 7 ] , in achieving regression of coronary artery lesions and reducing the clinical consequences of coronary artery disease [ 6 , 7 ] . However , risk factor interventions shown to be effective in clinical trials may not prove equally effective in clinical practice because of a paucity of re sources , especially nonphysician personnel . The lack of effective management systems limits the expected reduction in morbidity and mortality and the corresponding reduction in medical care costs that motivates current efforts to orient the priorities of the American health care system toward preventive and rehabilitative care . This r and omized , controlled trial compared the effectiveness of a physician-directed , nurse-managed , home-based case-management system for coronary risk factor modification with that of usual medical care . Outcomes were measured in both groups immediately after the end of the first year after acute myocardial infa rct ion . The term case-management system has been used in various context s. As used here , it refers to a system in which a nurse case-manager , working with different health care specialists ( a psychiatrist , a cardiologist , a lipid specialist , a nutritionist , and a nurse coordinator ) , managed coronary risk factors . Methods Enrollment and Orientation Program nurses enlisted patients on hospital day 3 or as soon as their medical condition stabilized . Study participants gave written informed consent to be r and omly assigned to a treatment group . Immediately after r and omization , program nurses introduced patients to the special intervention with the aid of a videotape . Usual Care The 585 patients in our study were cared for by 215 internists and 34 cardiologists in the five participating medical centers who were organized into practice groups of 5 to 10 physicians each . Cardiology consultation was often provided during hospitalization , but primary responsibility for follow-up care was generally assumed by internists . The usual care offered by the Kaiser Permanente Medical Care Program included physician counseling on smoking cessation and nutritionist counseling on dietary change during hospitalization and physician-managed , lipid-lowering drug therapy after hospital discharge . Group outpatient smoking cessation programs were available for a $ 50 fee . Group exercise rehabilitation , not generally provided by the Kaiser Permanente Medical Care Program during this study , was available to patients at various community facilities at an average cost of $ 1800 to $ 2700 for 3 months ' participation . Special Intervention The behavioral interventions in our case-management system , which were offered to the 293 patients in the intervention group in addition to usual care , were derived from social learning theory [ 8 , 9 ] and modified for medical problems [ 10 ] . In this model , persons must learn how to monitor the health habits they seek to change , set attainable sub goals to motivate and direct their efforts , use feedback of progress in ways that promote health , and enlist incentives and social support to sustain the effort needed to succeed [ 8 , 9 ] . In the hospital , patients were instructed on how to complete self-reports [ status reports ] of smoking , dietary intake , and exercise . Scheduled interactions between case managers and patients after discharge took three forms : 1 ) nurse-initiated telephone contacts ; 2 ) computer-generated progress reports mailed to patients based on question naires completed by patients and mailed to the nurses ; and 3 ) visits to the program nurse for treadmill exercise testing , initiation of lipid-lowering drug therapy , if indicated , and a single counseling session after a smoking relapse . The maximum number of treatment contacts during the year , including outcome measurement at 6 and 12 months , was as follows : 14 nurse-initiated telephone contacts , 8 patient visits to the blood chemistry laboratory , and 4 patient visits to the nurse case manager . Smoking Intervention Smoking was defined as the use of cigarettes , cigars , cigarillos , pipe tobacco , or any other form of tobacco in the 6 months before admission . Forty-three percent of patients were smokers . Patients who had smoked during the 6 months before hospitalization received the same intensive smoking cessation intervention during hospitalization ; this intervention has been described previously [ 11 ] . Physicians used a written script that enabled them to provide st and ardized counseling in less than 2 minutes . The hospital-based smoking cessation counseling focused on relapse prevention . Nurses conducted a st and ardized smoking history to evaluate patients ' addiction to smoking . Patients ' reported self-efficacy or confidence to resist smoking in each of 28 potentially high-risk situations was measured ; patients were then counseled on how to manage the situations in which they reported less than 70 % confidence . Patients also received a relapse prevention manual and a relaxation audiotape . They were advised that the nurse would telephone them 48 hours and 1 week after hospital discharge and at monthly intervals for as long as 6 months . Patients who relapsed were offered one additional visit with the nurse for further counseling . Nicotine polacrilex or transdermal nicotine patches were reserved for highly addicted patients who relapsed after hospital discharge . Nutritional Counseling A computer-based expert system developed by the investigators was used to provide nutritional counseling on a National Cholesterol Education Program [ 12 ] Step 2 diet that was low in cholesterol and saturated fat . A food frequency question naire design ed by the investigators was scored using the Cholesterol and Saturated Fat Index developed by Connor and colleagues [ 13 ] . Calculations of cholesterol and saturated fat totals were based on weekly rather than daily average food intakes . Data from the food frequency question naires , mailed by patients to the Stanford coordinating center and entered into a microcomputer , were used to generate progress reports that characterized patients ' dietary patterns , prioritized dietary change goals , and provided guides for managing difficult situations by directing patients to relevant sections of a nutrition workbook entitled Good Eating for Good Health developed by the program nutritionist . Patients in the intervention group completed a food frequency question naire during hospitalization that described their eating habits in the previous month . Patients also completed food frequency question naires 6 , 11 , and 26 weeks after admission . Progress reports were mailed to patients within 48 to 72 hours after the food frequency question naires were received . Detailed strategies for maintenance of dietary change were incorporated into the 26-week progress report . Question naires to evaluate outcomes were also completed at 36 and 52 weeks . Lipid-Lowering Drug Therapy The therapeutic goal of a plasma low-density lipoprotein (LDL)-cholesterol value of 2.46 mmol/L ( 95 mg/dL ) adopted for this trial was based on the mean post-treatment level of LDL cholesterol found in patients in the study by Blankenhorn and colleagues [ 4 ] . Patients with mean plasma LDL cholesterol values ( based on measurements in two separate blood sample s drawn 75 and 90 days after infa rct ion ) that exceeded this value were given initial drug therapy according to the four algorithms shown in Table 1 . Patients unable to tolerate bile acid-binding resin or nicotinic acid because of comorbid conditions or potentially adverse interactions with these agents received lovastatin or gemfibrozil . During a visit 90 days after discharge , the nurses did a brief physical examination and obtained a history relevant to hyperlipidemia . They provided detailed counseling to patients regarding the rationale for lipid-lowering drug therapy and ways to maximize drug efficacy and minimize drug side effects , and they advised patients on the schedule of laboratory visits and nurse-initiated follow-up telephone contacts . Table 1 . Initial Drug Therapy * Changes in drug therapy at 120 , 150 , and 180 days , which were coordinated by nurse-initiated telephone contacts , were based on three types of responses to initial therapy : 1 ) if lipoprotein levels returned to normal , the effective drug therapy was continued ; 2 ) if the response was incomplete , the dose of the effective medication was increased or another drug was added , or both ; and 3 ) if comorbid conditions worsened or blood chemistry abnormalities or intolerable side effects occurred , drug dosage was reduced or the patient was switched to another agent or both . A physician lipid specialist and a Stanford-based senior nurse-coordinator provided telephone consultation to the case managers . Before initiating lipid-lowering drug therapy at 90 days and at each subsequent step , nurses review ed the patients ' blood chemistry and lipoprotein values and elicited any symptoms requiring a change in therapy . The Physician-delivered , stop-smoking interventions significantly improve quit rates among smoking patients [ 1 - 6 ] . Unfortunately , only about one half of physicians in non research setting s consistently counsel smokers [ 7 - 11 ] , and fewer than one half of all smokers report that a physician has ever advised them to quit [ 12 - 14 ] . Given the pressures of routine medical practice , it is not surprising that physicians do not take 3 to 5 minutes to counsel every smoking patient they see . Tobacco counseling competes with other pressing clinical tasks ; physicians are often too busy to routinely and repeatedly counsel all patients who smoke [ 11 , 15 - 17 ] . Physicians will deliver a cessation protocol as part of a study [ 5 , 6 , 18 ] , but barriers such as a lack of time , training , and confidence make counseling in non research setting s less likely [ 1 , 4 , 19 , 20 ] . New approaches [ 21 - 23 ] , such as involving other office staff in counseling [ 17 , 24 , 25 ] , are needed if tobacco counseling is to become a consistent and sustainable part of medical care delivery [ 26 ] . Because physicians see roughly 70 % , or 38 million , of the 53 million smokers in the United States each year [ 15 ] , even a modestly effective physician-driven intervention would have considerable impact on the nation 's health . This study tested the feasibility and effectiveness of a team counseling approach design ed to minimize the burden on physicians by using non-physician clinic staff to provide the more time-consuming parts of cessation counseling . Key features of the team approach were a brief ( 30-second ) physician-delivered cessation message , referral to an on-site nurse or other staff for additional cessation support , and the use of videos to deliver much of the intervention in an efficient and st and ardized manner . A previous report of process and short-term outcome measures showed that this organized team approach proved practical and sustainable [ 27 ] . The participating physicians and other providers delivered brief advice to 86 % of identified smokers during the 1-year intake period , and most patients ( 87 % ) saw the counselor for material s and additional counseling . Nurse-Assisted counseling led to significantly improved quit rates at 3 months compared with brief physician advice alone . We present the effects of the intervention on long-term abstinence at 1 year . Methods Setting We conducted our study in two large primary care facilities of Kaiser Permanente Northwest Region , a group- practice health maintenance organization ( HMO ) in Portl and , Oregon . Receptionists asked patients between 18 and 70 years of age to complete a health habit survey while waiting for their visit . The patients were seeing 1 of 60 primary care physicians ( n = 42 ) , physician assistants ( n = 7 ) , or nurse practitioners ( n = 11 ) in outpatient internal medicine and family practice offices . Intervention Regular clinic nurses and clinical assistants collected the surveys as patients were taken to examination rooms and attached a notice to the medical charts of smokers ( n = 3161 ) to alert providers to deliver a brief stop-smoking advice message . Providers were oriented to their role in a 1-hour training session . They were encouraged to use their own words but to not go beyond the following basic 30-second message : The best thing you can do for your health is to stop smoking and I want to advise you to stop as soon as possible . I know it can be hard and many try several times before they finally make it . You may or may not want to stop now , but I want you to talk briefly with our health counselor , who has some tips to make stopping easier when you decide the time is right . The 2707 ( 86 % ) smokers who received the provider advice message were considered participants in the study , regardless of whether they were willing to see the counselor or had any interest in quitting smoking . By the end of follow-up , 16 patients died , leaving a total sample of 2691 . At the conclusion of the physician consultation , patients were seen by an on-site project nurse or health counselor who described what would be offered and obtained verbal consent to proceed . Patients who would not see the health counselor were mailed material s appropriate to their treatment assignment . Two r and om digits contained in the patient 's health record number were used to assign patients to one of the following four interventions : advice , self-quit , group-referral , or combination treatment . Physicians remained blind to treatment assignment . Advice participants received the 30-second provider advice message and a brief pamphlet , Why Do You Smoke ? , from the health counselor . This clear and systematic advice would probably be more effective than no treatment or usual care , which were not included for logistic and ethical reasons . The self-quit condition included cessation advice , a carbon monoxide assessment , and a 10-minute How to Quit Smoking video design ed specifically for this population . The video focused on the need to make a personal decision to quit , the steps to successful quitting , the frequent need for repeated efforts , and the importance of setting a specific quit date and using substitutes to smoking . The counselor provided a stop-smoking kit including smoking substitutes such as gum , toothpicks , and cinnamon sticks . A choice of one of three stop-smoking manuals was offered . Most participants chose the National Cancer Institute 's manual , Quit for Good ( 54 % ) , although others chose Calling it Quits ( 17 % ) or a two-part workbook produced by the American Lung Association titled , Freedom from Smoking in 20 Days and A Lifetime of Freedom from Cigarettes , respectively ( 29 % ) . Patients were encouraged to set a specific quit date or some other specific plan of action and the counselor arranged to call the patient , usually within 2 to 4 weeks , to check on progress toward cessation . Patients were also mailed a set of stop-smoking tip sheets and a series of six professionally design ed bimonthly newsletters devoted to smoking cessation . Group-referral participants also received advice , the carbon monoxide assessment , and a video . In this case , however , the video encouraged patients to join the HMO 's intensive stop-smoking group program known as Freedom from Cigarettes . This program entails nine group meetings over 2 months . In a recent study , this program achieved roughly a 35 % biochemically verified 1-year quit rate [ 28 ] . Patients were provided a brochure , a schedule of group sessions , and a time-limited coupon to waive the program fee . Efforts were made to schedule the patient for an upcoming group . Reminder postcards were sent 1 week before the scheduled meeting , and patients were called several days after the meeting to check on progress and , if necessary , to reschedule . Combination participants also received advice , the carbon monoxide assessment , and a third video , which described both the self-directed and the professionally led group approaches to smoking cessation . Self-directed cessation techniques , as well as the pros and cons of joining a professionally run program , were presented . Participants were asked to choose an approach that made sense for them . The self-help manual , stop-smoking kit , group material s , and fee-waiver coupon were all provided . Participants were encouraged to either set a quit date or sign up for a specific group session , and a telephone call was arranged to check on progress . Tip sheets and the bimonthly newsletters were mailed to all combination participants . Follow-up and Analyses Participants were surveyed by mail 3 and 12 months after their initial visits . Nonresponders were interviewed by telephone by an assessor who was blind to treatment assignment . Participants reporting abstinence from tobacco for at least 7 days before the 12-month assessment were asked to schedule appointments at a convenient clinic location or at their homes to provide saliva sample s for biochemical confirmation . The primary end point was a two-point prevalence measure , which was defined as consecutive abstinence at both the 3- and 12-month assessment s. Nonrespondents and those lost to follow-up were considered to be smokers . Results As shown in Table 1 , participants in the four treatment groups were similar in terms of baseline age , sex , race , education , occupation , cigarettes smoked per day , stage of change , confidence in ability to quit , perceived degree of overweight , and subjective health status [ 27 ] . Table 1 . Baseline Characteristics by Treatment Group * Self-reported smoking status was obtained on a high percentage of participants at both the 3-month ( 88 % ) and 12-month ( 86 % ) follow-up assessment s. Response rates did not differ significantly across treatment groups . The proportion of participants who reported one or more serious attempts to quit in the year following their clinic visit was significantly higher ( P < 0.004 ) among self-quit participants ( 53 % ) relative to advice participants ( 46 % ) . Group-referral ( 48 % ) and combination participants ( 50 % ) did not differ from advice participants in terms of quit attempts . All three nurse-assisted interventions self-quit , group referral , and combination result ed in higher 3-month point prevalence quit rates than did the advice treatment ( Table 2 ) . At the 12-month follow-up , a larger percentage of participants reported abstinence , although differences between treatment arms were reduced . The 12-month point prevalence definition of abstinence , however , includes both long-term ex-smokers and those who quit as little as 1 week before the 1-year follow-up . With the more conservative primary end point , consecutive abstinence at both the 3-month and 12-month assessment s , the three nurse-assisted interventions were superior to the advice intervention . Because quit rates for the three nurse-assisted interventions were similar for all analyses ( P > 0.2 ) , they were collapsed and compared to the advice intervention . Quit rates in the nurse-assisted groups were significantly higher than advice for the 3-month ( 6 OBJECTIVES This study evaluated a nurse-managed smoking cessation program for smokers hospitalized for a variety of conditions . METHODS Hospitalized patients who smoked prior to hospitalization and who were motivated to quit ( n = 660 ) were r and omized to intervention or usual-care groups and followed for the next year . The intervention included a meeting with the nurse-case manager ; the use of a videotape , workbook , relaxation audiotape , and nicotine replacement therapy ; and nurse-initiated phone contacts after discharge . RESULTS The 12-month confirmed cessation rates were 21 % and 31 % for , respectively , the usual-care and intervention groups ( odds ratio = 1.7 ; 95 % confidence interval = 1.1 , 2.3 ) . CONCLUSIONS A nurse-managed smoking cessation intervention can significantly increase cessation rates for hospitalized patients The authors evaluated whether completing a multi-item assessment of smoking craving ( the Question naire of Smoking Urges [ QSU ] ) promoted increases in smoking craving . A sample of 39 regular smokers was r and omly assigned to 1 of 3 manipulations ( each of 3 min duration ): ( a ) complete the QSU-Brief ( 10 items ) , ( b ) complete a noncraving question naire that was structurally identical to the QSU-Brief ( scale-based control ) , and ( c ) a time-based control . Participants responded to an oral question assessing their degree of craving immediately before and after the manipulations . Results indicated that the QSU did not promote increases in craving compared to the 2 control conditions . Despite continuing debate over the most appropriate self-report measure of craving , investigators who use the QSU-Brief can be reasonably sure that the scores that result are not biased due to reactivity effects STUDY OBJECTIVE To determine the effect of a nurse-managed intervention for smoking cessation in patients who have had a myocardial infa rct ion . DESIGN R and omized , with a 6-month treatment period and a 6-month follow-up . SETTING Kaiser Foundation hospitals in Redwood City , Santa Clara , Hayward , and San Jose , California . PATIENTS Sequential sample of 173 patients , 70 years of age or younger , who were smoking before hospitalization for acute myocardial infa rct ion . Eighty-six patients were r and omly assigned to the intervention and 87 to usual care ; 130 patients ( 75 % ) completed the study and were available for follow-up . INTERVENTION Nurse-managed and focused on preventing relapse to smoking , the intervention was initiated in the hospital and maintained thereafter primarily through telephone contact . Patients were given an 18-page manual that emphasized how to identify and cope with high-risk situations for smoking relapse . MEASUREMENTS AND MAIN RESULTS One year after myocardial infa rct ion , the smoking cessation rate , verified biochemically , was 71 % in the intervention group compared with 45 % in the usual care group , a 26 % difference ( 95 % CI , 9.5 % to 42.6 % ) . Assuming that all surviving patients lost to follow-up were smoking , the 12-month smoking cessation rate was 61 % in the intervention group compared with 32 % in the usual care group , a 29 % difference ( 95 % CI , 14.5 % to 43.5 % ) . Patients who either resumed smoking within 3 weeks after infa rct ion or expressed little intention of stopping in the hospital were unlikely to have stopped by 12 months . CONCLUSIONS A nurse-managed smoking cessation intervention largely conducted by telephone , initiated in the hospital , and focused on relapse prevention can significantly reduce smoking rates at 12 months in patients who have had a myocardial infa rct ion The authors compared 9- , 16- , 26- , and 52-week outcomes for two r and omly assigned groups of nicotine-dependent subjects : 1 ) nicotine patch plus four smoking cessation sessions with a nurse-practitioner giving advice and instruction ( n = 36 ; moderate-intensity condition , MI ) ; or 2 ) the foregoing treatments plus 16 weekly individual cognitive/ behavioral relapse-prevention therapy sessions ( n = 33 ; high-intensity condition , HI ) . Patch completion rates were 69.7 % in the HI group and 55.6 % in the MI group ( NS ) . Self-reported abstinence rates at the four follow-up points were comparable for the two treatment groups ; HI : 39 % , 36 % , 36 % , and 36 % ; MI : 44 % , 28 % , 25 % , and 28 % , respectively . There was some indication that MI patients with high nicotine dependence had lower abstinence rates than highly dependent HI patients This is a pilot study of a r and omized controlled trial of an individualized motivational intervention ( IMI ) provided by nurses to help smoking parents of sick children quit smoking . Eighty parents who brought their sick children to the hospital were entered into the study . The intervention group received an IMI from a trained nurse counselor and telephone reminders were given 1 week after the intervention . The quit rate at 1 month was 7.5 % ( 95 % CI , 0 - 21 ) in the intervention group and 2.5 % ( 95 % CI , 0 - 7 ) in the control group . Preliminary results indicated that the IMI provided by nurses seemed to be effective in helping resistant parents of sick children stop smoking . They also suggested that it was acceptable and feasible to implement such intervention in a pediatric outpatient clinic/ward in Hong Kong We tested an intervention to help smokers abstain ( fast ) from smoking before surgery , maintain abstinence postoperatively , and achieve long-term cessation . A r and omized experiment included 237 patients admitted for presurgical assessment who smoked . The intervention included counseling and nicotine replacement therapy . Treatment group participants ( 73.0 % ) were more likely to fast than were controls ( 53.0 % ) : chi(2)(1 , N = 228 ) = 8.89 , p = .003 , and more likely to be abstinent 6 months after surgery ( 31.2 % vs. 20.2 % ) . There was no significant difference in the abstinence rates at 12 months after surgery , chi(2)(1 , N = 169 ) < .001 , p = 1.00 . Encouraging patients to fast from smoking before surgery and postoperative support are efficacious ways to reduce preoperative and immediate post-operative tobacco use BACKGROUND Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit . Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to ( or spontaneously seek ) smoking cessation . METHOD Home health care nurses ( N = 98 ) were r and omly assigned to deliver either Motivational Enhancement ( ME ; Motivational Interviewing + Carbon Monoxide Feedback ) or St and ard Care ( AHCPR Guidelines for smoking cessation ) to their patients . Seventy percent of patients were eligible and willing to participate ( N = 273 ; 54 % female , mean age = 57 years , 83 % Caucasian , 41 % < high school education ) . The study was conducted in Providence , RI , USA from 1998 to 2003 . RESULTS Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2 % ( SC ) and 8.7 % ( ME ) for intent to treat analyses , and 5.2 % ( SC ) and 11.8 % ( ME ) using all available cases ( P > 0.05 ) . ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment ( all P values < 0.05 ) . CONCLUSIONS Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact A health education and counselling programme was offered to myocardial infa rct ion patients during and after hospitalization . A r and omized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention . During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication , healthy habits , anxiety and depression . On completion of these sessions , weekly telephone calls were made to patients for a period of six weeks after discharge from hospital . The intervention was offered to 30 myocardial infa rct ion patients and their partners ( the experimental group ) in addition to st and ard medical care . Thirty control patients received st and ard medical care only . Two months after myocardial infa rct ion , patients in the experimental condition reported a significantly greater increase in physical activity , and a significantly greater decrease in unhealthy eating habits . No effects were found regarding smoking cessation , anxiety and depression . Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits . No effects were found regarding smoking cessation , physical activity , anxiety and depression . In addition , two months after myocardial infa rct ion , it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating . Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation This study evaluated the impact of a nurse-led health education programme on the behaviour , nicotine dependence and nicotine withdrawal in patients who smoke and suffer from peripheral vascular disease , based in a large teaching hospital in the north of Engl and . Smoking behaviour was measured by self report , end-expired carbon monoxide and urinary cotinine . Nicotine dependence and withdrawal were measured using a nicotine dependence scale and a nicotine withdrawal scale . The findings demonstrated that the programme did have some impact on behaviour . The study raised issues concerning the measurement of physiological markers for smoking as nursing outcomes . Issues about the measurement of nicotine dependence and withdrawal are highlighted Abstract Objective : To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease . Design : Cluster r and omised controlled trial . Participants : 883 men and women selected for the presence of one or more modifiable risk factors : regular cigarette smoking , high serum cholesterol concentration ( 6.5 - 9.0 mmol/l ) , and high body mass index ( 25 - 35 ) combined with low physical activity . Intervention : Brief behavioural counselling , on the basis of the stage of change model , carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity . Main outcome measures : Question naire measures of diet , exercise , and smoking habits , and blood pressure , serum total cholesterol concentration , weight , body mass index , and smoking cessation ( with biochemical validation ) at 4 and 12 months . Results : Favourable differences were recorded in the intervention group for dietary fat intake , regular exercise , and cigarettes smoked per day at 4 and 12 months . Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months No differences were found between groups in changes in total serum cholesterol concentration , weight , body mass index , diastolic pressure , or smoking cessation . Conclusions : Brief behavioural counselling by practice nurses led to improvements in healthy behaviour . More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge UNLABELLED Patients with coronary artery disease ( CAD ) are at high risk of recurrent events . A healthy lifestyle can significantly reduce this risk . A previous trial , R and omized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists ( RESPONSE ) , demonstrated that nurse-coordinated outpatient clinics improve drug treatment of cardiovascular risk factors . However , lifestyle-related risk factors , including smoking , overweight , and physical inactivity , were common and remained largely unchanged at follow-up in most patients ( 66 % ) . The aim of the current study is to evaluate the impact of 3 community-based lifestyle programs in patients after hospitalization for CAD . We are conducting a multicenter ( n = 15 ) , r and omized trial that will recruit 800 patients to test the efficacy of up to 3 widely available commercial lifestyle programs , aim ed at patients and their partners , on top of usual care . These programs are aim ed at smoking cessation ( Luchtsignaal ( ® ) ) , weight loss ( Weight Watchers ( ® ) ) , and improving physical activity ( Philips DirectLife ( ® ) ) . OUTCOMES The primary outcome at 12months is the proportion of patients in whom at least 1 lifestyle risk factor is improved without deterioration in any of the other 2 , and a relative increase of at least 30 % in this proportion is considered clinical ly relevant This study was undertaken to evaluate a tailored smoking cessation intervention , which is applicable to Korean culture , using the Agency for Health Care Policy and Research ( AHCPR ) guideline . On-site counselors provided brief nurse-assisted smoking cessation counseling , including follow-up telephone support , to prevent a relapse in 200 r and omly assigned smoking patients . These patients were referred by their physicians regardless of their willingness in smoking cessation in the outpatient department at a university hospital . Nicotine replacement therapy was not provided . Another 201 patients served as a control . After 5 months , current smoking cessation was self-reported on the phone and vali date d later by a portable carbon monoxide analyzer . After 5 months , the participants in the intervention group were no more likely to quit smoking than the control group . A subgroup analysis by age showed that the intervention among 166 younger smokers ( aged 49 or less ) was significantly more likely to be effective { risk ratio = 5.76 [ 95 % confidence interval ( CI ) 1.34 - 24.74 ] } than it was among 235 older smokers ( aged 50 or more ) [ risk ratio = 1.03 ( 95 % CI 0.53 - 1.99 ) ] . This study suggests a smoking cessation intervention using the AHCPR guideline tailored for Koreans , is effective for assisting out patients aged 49 or younger to quit smoking OBJECTIVE To evaluate the effectiveness of a nurse led shared care programme to improve coronary heart disease risk factor levels and general health status and to reduce anxiety and depression in patients awaiting coronary artery bypass grafting ( CABG ) . DESIGN R and omised controlled trial . SETTING Community , January 1997 to March 1998 . STUDY GROUPS 98 ( 75 male ) consecutive patients were recruited to the study within one month of joining the waiting list for elective CABG at Glasgow Royal Infirmary University NHS Trust . Patients were r and omly assigned to usual care ( control ; n = 49 ) or a nurse led intervention programme ( n = 49 ) . INTERVENTION A shared care programme consisting of health education and motivational interviews , according to individual need , was carried out monthly . Care was provided in the patients ' own homes by the community based cardiac liaison nurse alternating with the general practice nurse at the practice clinic . OUTCOME MEASURES Smoking status , obesity , physical activity , anxiety and depression , general health status , and proportion of patients exceeding target values for blood pressure , plasma cholesterol , and alcohol intake . RESULTS Compared with patients who received usual care , those participating in the nurse led programme were more likely to stop smoking ( 25 % v 2 % , p = 0.001 ) and to reduce obesity ( body mass index > 30 kg/m2 ) ( 16.3 % v 8.1 % , p = 0.01 ) . Target systolic blood pressure improved by 19.8 % compared with a 10.7 % decrease in the control group ( p = 0.001 ) and target diastolic blood pressure improved by 21.5 % compared with 10.2 % in the control group ( p = 0.000 ) . However , there was no significant difference between groups in the proportion of patients with cholesterol concentrations exceeding target values . There was a significant improvement in general health status scores across all eight domains of the 36 item short form health survey with changes in difference in mean scores between the groups ranging from 8.1 ( p = 0.005 ) to 36.1 ( p < 0.000 ) . Levels of anxiety and depression improved ( p < 0.000 ) and there was improvement in time spent being physically active ( p < 0.000 ) . CONCLUSIONS This nurse led shared care intervention was shown to be effective for improving care for patients on the waiting list for CABG The purpose of this pilot study was to examine the effect of a structured smoking cessation intervention during hospitalization on short-term smoking abstinence . Hospitalized surgical oncology patients who smoked ( n = 26 ) and were diagnosed with cancer were r and omly assigned to either an experimental or control group . Experimental group subjects ( n = 12 ) received a structured smoking cessation intervention during hospitalization followed by five weekly phone calls after discharge . Control group subjects ( n = 14 ) received usual care from their health-care providers during hospitalization . Abstinence from smoking , as determined by saliva cotinine , the primary metabolite of nicotine , was measured at first postdischarge visit . Subjects with a saliva cotinine level of < 10 ng/ml were classified as abstinent . At first postdischarge visit , 75 % of experimental group subjects were abstinent compared with 42.9 % in the usual care group , a 32 % difference . These preliminary findings will assist in the design and further evaluation of cancer rehabilitation strategies promoting cessation in hospitalized postoperative cancer patients who continue to smoke Objective : To evaluate the feasibility and effectiveness of Nurse Based Motivational Interviewing ( N BMI ) on top of a routine patient based Lifestyle Inventory with Feedback ( LIFE ) in a cardiovascular outpatient secondary prevention setting . Methods : All current smokers ( n = 112 ) , identified in 619 successive patients with cardiovascular disease , were r and omized for either care as usual ( LIFE ) , or LIFE plus N BMI ( intervention group ) . Cumulative time investment was recorded . Results : After 3 months of follow-up , the abstinence rate in the control group was 7 % , and another 15 % diminished the number of cigarettes , whereas 26 % of intervention patients quit smoking ( p < 0.017 ) and another 31 % diminished smoking . On average , each completed motivational interviewing session took 63.5 min . Per quitter , time investment was 3.8 h and NNT appeared 5.9 . Conclusion : N BMI strategy on top of routinely administrated lifestyle self evaluation with professional feedback , significantly increases smoking cessation in an outpatient secondary prevention setting . Although cost effectiveness needs to be addressed , time investment per quitter in this approach appears low Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease ( COPD ) compared with usual care . Design 24 month , multicentre , pragmatic cluster r and omised controlled trial Setting 40 general practice s in the western part of the Netherl and s Participants Patients with COPD according to GOLD ( Global Initiative for COPD ) criteria . Exclusion criteria were terminal illness , cognitive impairment , alcohol or drug misuse , and inability to fill in Dutch question naires . Practice s were included if they were willing to create a multidisciplinary COPD team . Intervention General practitioners , practice nurses , and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice , including early recognition of exacerbations and self management , smoking cessation , physiotherapeutic reactivation , optimal diagnosis , and drug adherence . Additionally , the course served as a network platform and collaborating healthcare providers design ed an individual practice plan to integrate integrated disease management into daily practice . The control group continued usual care ( based on international guidelines ) . Main outcome measures The primary outcome was difference in health status at 12 months , measured by the Clinical COPD Question naire ( CCQ ) ; quality of life , Medical Research Council dyspnoea , exacerbation related outcomes , self management , physical activity , and level of integrated care ( PACIC ) were also assessed as secondary outcomes . Results Of a total of 1086 patients from 40 clusters , 20 practice s ( 554 patients ) were r and omly assigned to the intervention group and 20 clusters ( 532 patients ) to the usual care group . No difference was seen between groups in the CCQ at 12 months ( mean difference –0.01 , 95 % confidence interval –0.10 to 0.08 ; P=0.8 ) . After 12 months , no differences were seen in secondary outcomes between groups , except for the PACIC domain “ follow-up/coordination ” ( indicating improved integration of care ) and proportion of physically active patients . Exacerbation rates as well as number of days in hospital did not differ between groups . After 24 months , no differences were seen in outcomes , except for the PACIC follow-up/coordination domain . Conclusion In this pragmatic study , an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care , except improved level of integrated care and a self reported higher degree of daily activities . The contradictory findings to earlier positive studies could be explained by differences between interventions ( provider versus patient targeted ) , selective reporting of positive trials , or little room for improvement in the already well developed Dutch healthcare system . Trial registration Netherl and s Trial Register NTR2268 OBJECTIVE We prospect ively examined whether training home health care nurses is associated with changes in attitudes towards smoking cessation counseling and counseling behaviors . METHODS We trained 98 home health care nurses to deliver cessation counseling to their patients . Measures were administered at pre-training , post-training , and 6 months later . This was part of a larger study conducted in Providence , RI , USA ( 1998 - 2002 ) . RESULTS Compared with pre-training , at post-training , nurses reported significantly higher levels of self-efficacy to counsel , positive outcome expectations , optimism that patients would follow their advice , perceived worth of smoking counseling , perceived importance of quitting smoking , and perceived organizational support . These training effects were maintained 6 months later . Between the end of training and the 6-month follow-up , nurses reported significant increases in their perceived effectiveness to counsel smokers and confidence to encourage behavior change . Compared with pre-training , at 6 months of follow-up , nurses were significantly more likely to ask about smoking status , assess readiness to quit , advise to quit , assist with quitting , and arrange follow-up . Nurses spent significantly more time counseling smokers at 6 months than at pre-training , and were less likely to selectively counsel . CONCLUSIONS Brief training facilitates both short- and long-term changes in nurse attitudes and behaviors regarding smoking cessation counseling BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is predominantly caused by cigarette smoking and is considered a worldwide preventable chronic illness . Smoking cessation is considered the primary intervention for disease management and nurses should play a major role in assisting patients to stop smoking . Currently there is a lack of professional consensus on how cessation interventions should be evaluated . The vast array of biochemical markers reported in the literature can be confusing and can make the comparisons of results difficult . OBJECTIVE To vali date self-report data on smoking with exhaled carbon monoxide in patients with chronic obstructive pulmonary disease over twelve months . DESIGN We performed a secondary analysis of a previously published r and omized controlled trial evaluating nursing interventions to assist respiratory patients to stop smoking . SETTING Northern Irel and 's Regional Respiratory Centre . PARTICIPANTS A total of 91 cigarette smokers attending secondary care for the treatment for COPD participated in the study . METHOD Self-reported smoking status and cigarettes smoked per day were compared to exhaled carbon monoxide readings at baseline , 2 , 3 , 6 , 9 and 12 months . The cut-off value of ≤10 ppm was used to identify non-smokers . The p-values are based on Pearson 's correlation coefficient and Kappa Coefficient as appropriate . RESULTS Findings suggest self-reported smoking status and cigarette consumption amongst patients with chronic obstructive pulmonary disease was highly consistent with exhaled carbon monoxide results ( p = 0.001 - 0.003 ) . CONCLUSION The majority of patients with chronic obstructive pulmonary disease reliably report their cigarette consumption This study aim ed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking . Using a single general practitioner visit backed up by a practice nurse , 14 % of the smokers had discontinued the habit 6 months after the intervention period . The intervention group also showed some improvements in a st and ardized measure of breathlessness AIMS To examine the influence of risk perception on intentions to quit smoking and post-treatment abstinence . DESIGN Prospect i ve and longitudinal . SETTING United States . PARTICIPANTS A total of 237 adult smokers ( mean age 56 years ) receiving medical care from home health-care nurses . Participants did not have to want to quit smoking to participate , but received cessation counseling within the context of their medical care . MEASUREMENTS Three measures of risk perception were given pre- and post-treatment : perceived vulnerability , optimistic bias and pre caution effectiveness . Smoking status was verified biochemically at end of treatment and at 2 , 6 and 12 months later . FINDINGS Principal components analysis supported the theoretical discriminability of the risk perception measures , and intercorrelations provided evidence for concurrent and predictive validity . Elevated risk perception was associated with a variety of socio-demographic and psychosocial characteristics . Optimistic bias was associated significantly with older age and ethnic minority status . Smokers in pre-contemplation had lower perceived vulnerability and pre caution effectiveness and greater optimistic bias than those in contemplation and preparation . Smokers in preparation had higher perceived vulnerability and lower optimistic bias than those in earlier stages . Change in perceived vulnerability predicted smoking cessation at follow-up . Optimistic bias predicted a lower likelihood of cessation and pre caution effectiveness predicted a greater likelihood of smoking cessation , but only among those with a smoking-related illness . CONCLUSIONS In patients receiving medical care from home health-care nurses , change in perceived vulnerability to smoking-related disease is predictive of smoking cessation . In those with smoking-related illnesses , optimistic bias predicts continued smoking while pre caution effectiveness predicts cessation OBJECTIVES In 1986 , the state health departments of Colorado , Maryl and , and Missouri conducted a federally-funded demonstration project to increase smoking cessation among pregnant women receiving prenatal care and services from the Women , Infants , and Children ( WIC ) program in public clinics . METHODS Low-intensity interventions were design ed to be integrated into routine prenatal care . Clinics were r and omly assigned to intervention or control status ; pregnant smokers filled out question naires and gave urine specimens at enrollment , in the eighth month of pregnancy , and postpartum . Urine cotinine concentrations were determined at CDC by enzyme-linked immunosorbent assay and were used to verify self-reported smoking status . RESULTS At the eighth month of pregnancy , self-reported quitting was higher for intervention clinics than control clinics in all three states . However , the cotinine-verified quit rates were not significantly different . CONCLUSIONS Biochemical verification of self-reported quitting is essential to the evaluation of smoking cessation interventions . Achieving changes in smoking behavior in pregnant women with low-intensity interventions is difficult Abstract Objectives : To evaluate the effects of nurse led clinics in primary care on secondary prevention , total mortality , and coronary event rates after four years . Design : Follow up of a r and omised controlled trial by postal question naires and review of case notes and national data sets . Setting : Stratified , r and om sample of 19 general practice s in north east Scotl and . Participants : 1343 patients ( 673 intervention and 670 control ) under 80 years with a working diagnosis of coronary heart disease but without terminal illness or dementia and not housebound . Intervention : Nurse led secondary prevention clinics promoted medical and lifestyle components of secondary prevention and offered regular follow up for one year . Main outcome measures : Components of secondary prevention ( aspirin , blood pressure management , lipid management , healthy diet , exercise , non-smoking ) , total mortality , and coronary events ( non-fatal myocardial infa rct ions and coronary deaths ) . Results : Mean follow up was at 4.7 years . Significant improvements were shown in the intervention group in all components of secondary prevention except smoking at one year , and these were sustained after four years except for exercise . The control group , most of whom attended clinics after the initial year , caught up before final follow up , and differences between groups were no longer significant . At 4.7 years , 100 patients in the intervention group and 128 in the control group had died : cumulative death rates were 14.5 % and 18.9 % , respectively ( P=0.038 ) . 100 coronary events occurred in the intervention group and 125 in the control group : cumulative event rates were 14.2 % and 18.2 % , respectively ( P=0.052 ) . Adjusting for age , sex , general practice , and baseline secondary prevention , proportional hazard ratios were 0.75 for all deaths ( 95 % confidence intervals 0.58 to 0.98 ; P=0.036 ) and 0.76 for coronary events ( 0.58 to 1.00 ; P=0.049 ) Conclusions : Nurse led secondary prevention improved medical and lifestyle components of secondary prevention and this seemed to lead to significantly fewer total deaths and probably fewer coronary events . Secondary prevention clinics should be started sooner rather than later . What is already known on this topic Several effective interventions exist for the secondary prevention of coronary heart disease , but implementing them in practice has proved difficult Secondary prevention programmes for coronary heart disease have improved short term outcomes such as processes of care and quality of life What this study adds Short term improvements in uptake of secondary prevention produced by nurse led clinics are maintained in the longer term Improved medical and lifestyle components of secondary prevention produced by nurse led clinics seem to lead to fewer total deaths and coronary OBJECTIVES This report analyzes cigarette smoking over 10 years in population s in the World Health Organization ( WHO ) MONICA Project ( to monitor trends and determinants of cardiovascular disease ) . METHODS Over 300,000 r and omly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined population s. RESULTS For men , smoking prevalence decreased by more than 5 % in 16 of the 36 study population s , remained static in most others , but increased in Beijing . Where prevalence decreased , this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting . Among women , smoking prevalence increased by more than 5 % in 6 population s and decreased by more than 5 % in 9 population s. For women , smoking tended to increase in population s with low prevalence and decrease in population s with higher prevalence ; for men , the reverse pattern was observed . CONCLUSIONS These data illustrate the evolution of the smoking epidemic in population s and provide the basis for targeted public health interventions to support the WHO priority for tobacco control Objective . To evaluate whether smoking cessation after a coronary event improves quality of life , and to assess whether quality of life is a predictor of smoking cessation . Design . Health-related quality of life at baseline and at 12 months follow up were measured in a r and omised smoking cessation trial of 240 smokers aged under 76 years admitted for myocardial infa rct ion , unstable angina or coronary bypass surgery . At 12 months follow up 101 had managed to give up smoking ( quitters ) , and 117 were smokers ( sustained smokers ) . Results . The quitters and sustained smokers had similar improvements in all quality of life domains from baseline to 12 months follow up . Further , after adjustment for differences in baseline characteristics , the quality of life was not significantly different in the quitters compared to the sustained smokers neither at baseline nor at 12 months follow up . Conclusions . Smoking cessation did not improve quality of life compared to sustained smoking after a coronary event in a 12 month follow up . Quality of life was not a significant predictor of smoking cessation BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients BACKGROUND Tobacco cessation after acute myocardial infa rct ion ( AMI ) substantially improves outcome but how effective individual programmes are needs to be established . To date , few studies have examined this factor . AIMS To assess the outcome of two smoking cessation programmes after AMI . METHODS One hundred and ninety-eight current smokers admitted to coronary care with an AMI participated in a r and omized controlled study comparing two outpatient tobacco interventions , the Stanford Heart Attack Staying Free ( SF ) programme and a Usual Care ( UC ) programme . RESULTS Log-rank analyses revealed that patients in the SF programme were retained longer ( P < 0.001 ) and had higher cotinine vali date d abstinence rates ( P < 0.001 ) compared with patients in the UC programme . Twelve months after intervention , 39 % of the SF programme compared with 2 % of the UC programme demonstrated cotinine vali date d tobacco cessation , representing a significant reduced relapse rate in the SF programme ( chi2 , P < 0.001 ) . CONCLUSIONS The SF smoking cessation programme initiated in hospital can significantly reduce smoking rates at 12 months after myocardial infa rct ion . Although superior to the UC quit programme , Australian outcomes were lower than the American programme originators ' published outcomes Background Smoking cessation is probably the most important action to reduce mortality after a coronary event . Smoking cessation programs are not widely implemented in patients with coronary heart disease , however , possibly because they are thought not to be worth their costs . Our objectives were to estimate the cost effectiveness of a smoking cessation program , and to compare it with other treatment modalities in cardiovascular medicine . Methods A cost-effectiveness analysis was performed on the basis of a recently conducted r and omized smoking cessation intervention trial in patients admitted for coronary heart disease . The cost per life year gained by the smoking cessation program was derived from the re sources necessary to implement the program , the number needed to treat to get one additional quitter from the program , and the years of life gained if quitting smoking . The cost effectiveness was estimated in a low-risk group ( i.e. patients with stable coronary heart disease ) and a high-risk group ( i.e. patients after myocardial infa rct ion or unstable angina ) , using survival data from previously published investigations , and with life-time extrapolation of the survival curves by survival function modeling . Results In a lifetime perspective , the incremental cost per year of life gained by the smoking cessation program was ∊280 and ∊110 in the low and high-risk group , respectively ( 2000 prices ) . These costs compare favorably to other treatment modalities in patients with coronary heart disease , being approximately 1/25 the cost of both statins in the low-risk group and angiotensin-converting enzyme inhibitors in the high-risk group . In a sensitivity analysis , the costs remained low in a wide range of assumptions . Conclusions A nurse-led smoking cessation program with several months of intervention is very cost-effective compared with other treatment modalities in patients with coronary heart disease BACKGROUND Brief advice to stop smoking from general practitioners ( GPs ) has been repeatedly shown to increase smoking cessation by a small , but measurable amount . Some studies have suggested that adding more intensive interventions to brief advice may increase its effectiveness , but it is unclear whether this is true in general practice . AIMS To determine whether brief advice from a doctor together with counselling and follow-up from a trained practice nurse is more effective than brief advice alone in helping people to stop smoking . METHODS The design was a r and omized controlled trial . Four hundred and ninety-seven general practice patients aged older than 18 years and smoking at least one cigarette per day in six general practice s in Oxfordshire , Berkshire , and Buckinghamshire were r and omized to one of two interventions : brief verbal or written advice from a GP plus extended counselling and follow-up from a trained practice nurse ; brief advice from a GP alone . The primary outcome was sustained abstinence from smoking at three and 12 months . A secondary outcome was forward movement in the stages of change cycle . RESULTS The proportion showing sustained abstinence was 3.6 % in the extended counselling group , and 4.4 % in the brief advice group ( difference = -0.8 % ; 95 % confidence interval = -4.3 % to 2.6 % ) . Seventy-four ( 30 % ) of those r and omized to extended counselling actually took up this offer . No significant progression in stages of change was detected between the two groups . CONCLUSIONS In unselected general practice patients who smoke , brief advice from a GP combined with intensive intervention and follow-up by a practice nurse is no more effective than brief advice alone abstract Objective To determine whether a nurse led smoking cessation intervention affects smoking cessation rates in patients admitted for coronary heart disease . Design R and omised controlled trial . Setting Cardiac ward of a general hospital , Norway . Participants 240 smokers aged under 76 years admitted for myocardial infa rct ion , unstable angina , or cardiac bypass surgery . 118 were r and omly assigned to the intervention and 122 to usual care ( control group ) . Intervention The intervention was based on a booklet and focused on fear arousal and prevention of relapses . The intervention was delivered by cardiac nurses without special training . The intervention was initiated in hospital , and the participants were contacted regularly for at least five months . Main outcome measure Smoking cessation rates at 12 months determined by self report and biochemical verification . Results 12 months after admission to hospital , 57 % ( n = 57/100)of patients in the intervention group and 37 % ( n = 44/118 ) in the control group had quit smoking ( absolute risk reduction 20 % , 95 % confidence interval 6 % to 33 % ) . The number needed to treat to get one additional person who would quit was 5 ( 3 to 16 ) . Assuming all dropouts relapsed at 12 months , the smoking cessation rates were 50 % in the intervention group and 37 % in the control group ( absolute risk reduction 13 % , 0 % to 26 % ) . Conclusion A smoking cessation programme delivered by cardiac nurses without special training , significantly reduced smoking rates in patients 12 months after admission to hospital for coronary heart disease BACKGROUND In an effort to find more practical smoking intervention models for primary -care setting s , three physician- and -nurse team approaches to patient counseling were compared with brief physician advice alone . METHODS Subjects were 3,161 adult smokers surveyed while waiting to see 1 of 40 primary -care physicians . Physicians delivered a brief stop-smoking prompt to 2,707 ( 86 % ) of these smokers and referred them to an on-site smoking counselor ( e.g. , nurse ) who r and omly provided a two-page pamphlet ( advice-only control ) or one of three brief nurse-assisted interventions : ( a ) self-quit training , ( b ) recruitment to a group program , or ( c ) a combination intervention . Smokers usually ( 87 % ) agreed to see the counselor . RESULTS After 3 months , subjects in the three nurse-assisted conditions were more likely to report a serious quit attempt ( 50 % vs 39 % , P less than 0.001 ) than were physician-advice-only subjects . Quit rates at 3 months were also higher ( P less than 0.001 ) in the nurse-assisted self-quit ( 12.9 % ) , recruitment ( 14.1 % ) , and combination ( 13.0 % ) conditions , compared with those for brief physician advice only ( 7.6 % ) . CONCLUSION If long-term efficacy is confirmed , these nurse-assisted counseling approaches will serve as practical smoking intervention models for most medical-care delivery setting OBJECTIVE To examine the relative effectiveness of three different presentations of a smoking cessation program on the smoking behavior of adults with cardiovascular health problems . DESIGN A 2 x 2 x 2 x 4 experimental design with stratification by sex , smoking history , and a cardiovascular event , and r and omization to Individual , Group , Written , or No Intervention groups . SETTING Six community hospital classrooms . SUBJECTS 255 nonhospitalized adults . THEORETIC FRAMEWORK : Interaction Model of Client Health Behavior . MEASUREMENTS Study Intake : Professional referral form , demographic question naire , smoking habits question naire , health history , perceived threat survey , perceived health status . Follow up : smoking cessation and health question naire , saliva thiocyanate testing . RESULTS At 12-month follow-up , a nurse-client interaction was more effective than written self-help material s ; however , smoking cessation rates were highest in the No Intervention control group , possibly related to having had coronary artery bypass graft surgery . Variables positively related to quitting were being male and married and having a higher income . With baseline factors considered , a quitter was most likely to be male and less than 48 years of age , have a high degree of perceived threat relative to medical diagnosis , and be in the individual intervention group . Only partial support for the study hypotheses was found Background : Programs for smoking cessation for cardiac patients are underused in Canada . We examined the efficacy of an intervention for smoking cessation for patients admitted to hospital for coronary artery bypass graft ( CABG ) or because of acute myocardial infa rct ion ( MI ) . Methods : Nurses r and omly assigned 276 sequential patients admitted because of acute MI or for CABG who met the inclusion criteria . Participants received an intensive or minimal smoking-cessation intervention . The minimal intervention included advice from physicians and nurses and 2 pamphlets . The intensive intervention included the minimal intervention plus 60 minutes of bedside counselling , take-home material s and 7 nurse-initiated counselling calls for 2 months after discharge . The outcomes were point prevalence of abstinence at 3 , 6 and 12 months after discharge . Results : The 12-month self-reported rate of abstinence was 62 % among patients in the intensive group and 46 % among those in the minimal group ( odds ratio [ OR ] 2.0 , 95 % confidence interval [ CI ] 1.2–3.1 ) . Abstinence was confirmed for 54 % of patients in the intensive group and 35 % in the minimal group ( OR 2.0 , 95 % CI 1.3–3.6 ) . Abstinence was significantly lower among those who used pharmacotherapy than among those who did not ( p < 0.001 ) . Continuous 12-month abstinence was 57 % in the intensive group and 39 % in the minimal group ( p < 0.01 ) . It was significantly higher among patients admitted for CABG than among those admitted because of acute MI ( p < 0.05 ) . Interpretation : Providing intensive programs for smoking cessation for patients admitted for CABG or because of acute MI could have a major impact on health and health care costs BACKGROUND People with severe mental ill health are three times more likely to smoke but typically do not access conventional smoking cessation services , contributing to widening health inequalities and reduced life expectancy . We aim ed to pilot an intervention targeted at smokers with severe mental ill health and to test methods of recruitment , r and omisation , and follow up before implementing a full trial . METHODS The Smoking Cessation Intervention for Severe Mental Ill Health Trial ( SCIMITAR ) is a pilot r and omised controlled trial of a smoking cessation strategy design ed specifically for people with severe mental ill health , to be delivered by mental health nurses and consisting of behavioural support and drugs , compared with a conventional smoking cessation service ( ie , usual care ) . Adults ( aged 18 years or older ) with bipolar disorder or schizophrenia , who were current smokers , were recruited from NHS primary care and mental health setting s in the UK ( York , Scarborough , Hull , and Manchester ) . Eligible participants were r and omly allocated to either usual care ( control group ) or usual care plus the bespoke smoking cessation strategy ( intervention group ) . R and omisation was done via a central telephone system , with computer-generated r and om numbers . We could not mask participants , family doctors , and research ers to the treatment allocation . Our primary outcome was smoking status at 12 months , verified by carbon monoxide measurements or self-report . Only participants who provided an exhaled CO measurement or self-reported their smoking status at 12 months were included in the primary analysis . The trial is registered at IS RCT N.com , number IS RCT N79497236 . FINDINGS Of 97 people recruited to the pilot study , 51 were r and omly allocated to the control group and 46 were assigned to the intervention group . Participants engaged well with the bespoke smoking cessation strategy , but no individuals assigned to usual care accessed NHS smoking cessation services . At 12 months , 35 ( 69 % ) controls and 33 ( 72 % ) people assigned to the intervention group provided a CO measurement or self-reported their smoking status . Smoking cessation was highest among individuals who received the bespoke intervention ( 12/33 [ 36 % ] vs 8/35 [ 23 % ] ; adjusted odds ratio 2·9 , 95 % CI 0·8 - 10·5 ) . INTERPRETATION We have shown the feasibility of recruiting and r and omising people with severe mental ill health in a trial of this nature . The level of engagement with a bespoke smoking cessation strategy was higher than with a conventional approach . The effectiveness and safety of a smoking cessation programme design ed particularly for people with severe mental ill health should be tested in a fully powered r and omised controlled trial . FUNDING National Institute of Health Research Health Technology Assessment Programme AIM To examine the effectiveness of a stage-matched smoking cessation counselling intervention for smokers who had cardiac diseases . METHODS A total of 1860 Chinese cardiac patients who smoked at least one cigarette in the past 7 days and aged 18 years or above recruited from cardiac out-patient clinics in Hong Kong hospitals were allocated r and omly to an intervention group or control group . The intervention group ( n = 938 ) received counselling matched with their stage of readiness to quit by trained counsellors at baseline , 1 week and 1 month . The control group ( n = 922 ) received brief counselling on healthy diet at baseline . The primary outcomes were self-reported 7-day and 30-day point prevalence ( PP ) of tobacco abstinence at 12 months after baseline . The secondary outcome measures included biochemically vali date d abstinence at 12-month follow-up , self-reported 7-day and 30-day PP abstinence and reduction of cigarette consumption by 50 % at 3 and 6 months . RESULTS By intention-to-treat analysis , the intervention and control groups showed no significant difference in self-reported 7-day PP abstinence ( intervention : 26.5 % versus control : 25.5 % ; P = 0.60 ) and 30-day PP ( intervention : 25.4 % versus control : 24.2 % ; P = 0.55 ) , biochemically vali date d abstinence ( intervention : 6.6 % versus control : 4.9 % ; P = 0.14 ) and overall quit attempts of least 24 hours ( intervention : 40.3 % versus control : 34.3 % ; P = 0.007 ) at the 12-month follow-up , adjusted for the baseline stage of readiness to quit smoking . CONCLUSIONS An intervention , based on the Stages of Change model , to promote smoking cessation in cardiac patients in China failed to find any long-term benefit AIM To evaluate the effectiveness of a nurse intervention aim ed at helping college student smokers quit smoking . DESIGN Single-blind , pragmatic r and omized controlled trial which compares a multi-component intervention , tailored specifically to college students , with a brief advice session with a 6-month follow-up . SETTING S This study was conducted at the University of Navarra , Spain . PARTICIPANTS A total of 255 college student smokers ( age range = 18 - 24 years ) were r and omized to an intervention group ( n = 133 ) or to a control group ( n = 122 ) . INTERVENTION A multi-component intervention based on the Theory of Triadic Influence of Flay was developed . The intervention consisted of a 50-minute motivational interview conducted by a nurse and online self-help material . The follow-up included a reinforcing e-mail and group therapy . MEASUREMENTS The primary outcome was self-reported abstinence , with biochemical verification at 6 months . The secondary outcomes consisted of the mean number of cigarettes smoked per day , self-reported attempts to quit smoking and stage of change at 6 months . FINDINGS At the 6-month follow-up , the smoking cessation incidence was 21.1 % in the intervention group compared with 6.6 % in the control group ( difference = 14.5 confidence interval = 6.1 - 22.8 ; relative risk = 3.41 , 95 % confidence interval = 1.62 - 7.20 ) . The difference in the mean number of cigarettes at 6 months was significantly different ( difference = -2.2 , confidence interval = -3.6 to -0.9 ) . CONCLUSIONS A multi-component intervention tailored to college students and managed by a nurse is effective in increasing smoking cessation among college students Tobacco smoking is a major risk factor for cardiovascular disease [ 1 ] . Smokers who quit reduce their coronary heart disease morbidity and mortality rates , even after the onset of clinical disease . Smokers who quit after a myocardial infa rct ion have lower reinfa rct ion rates and longer survival than do those who continue to smoke [ 2 ] . The relation between smoking and the outcome of coronary artery bypass graft surgery is less well studied , but in one study , smokers who quit after surgery had better survival , fewer attacks of angina , and fewer hospitalizations during a 10-year period [ 3 , 4 ] . Pathologic and angiographic studies show less late saphenous vein graft occlusion in smokers who quit after surgery than in those who do not [ 5 , 6 ] . Neither the pattern nor predictors of smoking cessation after coronary artery bypass graft surgery have been well studied . The operation may induce smoking cessation , because myocardial infa rct ion and newly diagnosed coronary artery disease do so [ 2 , 7 - 9 ] . Approximately one third of smokers quit smoking after having a myocardial infa rct ion [ 2 , 9 , 10 ] . Patients scheduled for coronary bypass surgery , like patients who have myocardial infa rct ion , face a potentially life-threatening event related to coronary heart disease , one requiring hospitalization for at least 1 week . However , coronary bypass surgery is often elective , whereas myocardial infa rct ion may be an unexpected complication of an undiagnosed condition . Consequently , patients may be less motivated to stop smoking after bypass surgery than they are after myocardial infa rct ion . In a r and omized trial of coronary artery bypass surgery , 25 % of smokers assigned to surgery stopped smoking in the year after the operation , and smoking rates remained constant for the next 5 years [ 11 ] . Two newer studies reported higher cessation rates ( 31 % and 55 % ) [ 12 , 13 ] . None of these studies vali date d self-reported smoking status at follow-up or identified factors associated with nonsmoking . Even less is known about the success of smoking interventions in patients having coronary bypass surgery . In-hospital intervention boosts the cessation rate after myocardial infa rct ion [ 10 , 14 ] , but whether it will do so after bypass surgery is unknown . To determine this , we developed a smoking cessation program for in patients recovering from coronary artery bypass surgery and tested its effectiveness in a r and omized , controlled trial . We chose this approach because patients who undergo coronary bypass surgery spend a median of 11 days in the hospital after surgery [ 15 ] . During this time , they are not permitted to smoke , can be easily reached by an intervention team , and may be highly motivated to quit . We reasoned that we could take advantage of this period of enforced nonsmoking to teach smokers the skills to remain abstinent after discharge . We also tried to identify factors associated with sustained nonsmoking to guide future intervention efforts . Methods Recruitment and R and omization This trial was conducted in the postoperative cardiac surgery unit at Massachusetts General Hospital . During 1 year ending 1 July 1987 , we review ed the charts of all 672 patients scheduled for coronary artery bypass surgery by six participating surgeons ( 82 % of all such procedures ) . A research nurse recruited patients who met eligibility criteria : those who had smoked at least 1 pack of cigarettes in the past 6 months , lived in eastern Massachusetts or Rhode Isl and , spoke English , and were not too ill to participate . We included both current smokers and recent ( < 6 months ) quitters because of the high relapse rates known to follow smoking cessation . Of 672 patients scheduled for the surgery , 152 ( 23 % ) were current smokers or had quit within 6 months . Of 120 patients meeting eligibility criteria , 93 ( 78 % ) agreed to participate . Reasons for refusals were insufficient time to collect baseline data ( n = 8) , too much stress ( n = 6 ) , no desire to quit ( n = 6 ) , or perceived ability to quit without assistance ( n = 3 ) . Patients were r and omly assigned to control or intervention groups after surgery . Intervention began when the patient was physically able to participate , generally on the fourth day after operation . Four participants were lost before r and omization ( surgery was canceled for 3 and 1 died ) , and 89 patients were r and omly assigned to control or intervention groups . Two patients , one in each group , died before discharge , when outcome was first assessed . This report is based on the 87 patients ( 43 controls , 44 patients receiving the intervention ) who were discharged alive . Intervention The intervention was a smoking cessation and relapse prevention program adapted from the American Lung Association 's In Control program , which teaches cognitive and behavioral smoking cessation techniques [ 16 ] . We used edited portions of the videotape and manual to produce a st and ardized , three-session program delivered by the study nurse to individual patients . Family members were encouraged to attend . Total counseling time was 60 minutes . One week after discharge , the nurse called each participant to offer support and brief counseling . Patients in the control group received usual postoperative care , including brief advice not to smoke as part of a group lecture . In patients were not permitted to smoke by hospital policy . Assessment Patients completed a baseline data form before surgery . It assessed demographic factors ( age , sex , ethnic background , education , and employment status ) , functional status [ 17 ] , smoking history ( pack-years and daily cigarette consumption ) , degree of nicotine addiction [ 18 ] , current symptoms of nicotine withdrawal [ 19 ] , previous attempts to quit smoking ( number of attempts , duration , difficulty , and method ) , level of social support for nonsmoking , percentage of household members and friends who smoke , knowledge and attitudes about smoking and heart disease ( 15 items ) , duration of nonsmoking before surgery , intention to quit after surgery , and confidence in their ability to quit . Charts were review ed for medical history , severity of heart disease ( frequency of angina attacks , number of myocardial infa rct ions , previous bypass surgery or angioplasty , left ventricular function on angiogram , and number of coronary vessels occluded and bypassed ) , and hospital course ( length of stay and occurrence of 12 complications ) . The primary outcome variable was smoking behavior , assessed by self-report and vali date d by saliva cotinine assay [ 20 ] . Smoking status was monitored at hospital discharge and 2 weeks and 2 , 4 , 8 , and 12 months later . It was also assessed in September 1992 , a median of 5.5 years after discharge ( range , 60 to 72 months ) . At 1 and 5.5 years , self-reported nonsmoking was vali date d by saliva cotinine assay [ 20 ] . Sample s were obtained by mail , a method previously shown to accurately identify smokers and nonsmokers [ 21 ] . Individuals who did not provide saliva sample s or whose cotinine concentrations were more than 20 ng/mL were considered smokers [ 22 ] . Death certificate data were review ed to identify patients lost to follow-up . Eighty patients ( 92 % ) were alive 1 year after discharge , and smoking status was determined in all of them . Seventy patients ( 80 % ) were alive at 5.5 years , and smoking status was assessed in 66 ( 94 % ) . More than 90 % of follow-up information was obtained by telephone . If this was not possible , patients were sent a written form . Other variables assessed at follow-up were nicotine withdrawal symptoms , attitudes and beliefs about smoking , confidence in the ability to quit , health status , and functional status . We also monitored co interventions , including attendance at a cardiac rehabilitation or smoking cessation program , interim hospitalization , and use of nicotine gum . ( Transdermal nicotine was not available during the study period . ) Data Analysis Two outcome rates were calculated : continuous nonsmoking ( no smoking since hospital discharge ) and current nonsmoking ( no smoking for the past week ) [ 23 ] . Following st and ard practice , patients lost to follow-up and patients whose reports of nonsmoking were not vali date d biochemically were counted as smokers when calculating cessation rates [ 23 ] . We excluded these patients and repeated the calculations . To identify factors associated with smoking cessation , we compared smokers and nonsmokers 1 and 5.5 years after surgery . To minimize misclassification of smoking status in these analyses , we excluded patients lost to follow-up and nonsmokers whose self-report was not vali date d biochemically . We compared differences in proportions and means between groups using chi-square tests and Student t-tests , respectively . Variables associated with nonsmoking at the P < 0.05 level were entered into backward stepwise , multiple logistic regression models , and odds ratios with 95 % CIs were calculated . Age , sex , and education level were included in all multivariate models . Significance tests were two-tailed . Results Comparison of Groups at Baseline No statistically significant differences were found between control and intervention groups at study entry or during hospitalization ( Table 3 ) . The typical participant was a middle-aged , white man with a high school education who smoked 1.5 packs each day and had a 58 pack-year smoking history . Participants had made an average of 2.5 attempts to quit smoking , but only 14 % had attended a formal program . Although 79 % of patients had been told to abstain from cigarettes before surgery , 48 % smoked in the week before admission and 15 % smoked in the hospital before surgery . In contrast , 38 % abstained from tobacco for more than 1 month before admission and 19 % did not smoke for more than 3 months . As a group , participants knew that smoking contributed to their heart disease and believed that they would benefit from quitting . They were strongly motivated to quit smoking after surgery and expected some difficulty but were confident of success . They felt strong social support for Abstract Objective : To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice . Design : R and omised controlled trial . Setting : Five urban general practice s in Bedfordshire . Subjects : 2136 patients receiving an initial health check in 1989 - 91 and scheduled to be re-examined one year later in 1990 - 2 ( intervention group ) ; 3988 patients receiving an initial health check in 1990 - 2 ( control group ) . All patients were aged 35 - 64 years at recruitment in 1989 . Main outcome measures : Serum total cholesterol concentration , blood pressure , body mass index , confirmed smoking cessation . Results : Mean serum total cholesterol was 2.3 % lower in the intervention group than in the controls ( difference 0.14 mmol/l ( 95 % confidence interval 0.08 to 0.20 ) ) ; the difference was greater in women ( 3.2 % , P<0.0001 ) than men ( 1.0 % , P=0.18 ) . There was no significant difference in smoking prevalence , quit rates , or body mass index . Systolic and diastolic blood pressure were 2.5 % and 2.4 % lower respectively in the intervention group . The proportion of patients with diastolic blood pressure > = 100 mm Hg was 2.6 % ( 55/2131 ) in the intervention group and 3.4 % ( 137/3987 ) in the controls ( difference 0.9 % ( 0.0 to 1.7 ) ; the proportion with total cholesterol concentration > = 8 mmol/l 4.8 % ( 100/2068 ) and 7.6 % ( 295/3905 ) ( difference 2.7 % ( 1.5 to 4.0 ) ) ; and that with body mass index > = 30 12.4 % ( 264/2125 ) and 14.0 % ( 559/3984 ) ( difference 1.6 % ( -0.2 to 3.4 ) ) . Conclusion : General health checks by nurses are ineffective in helping smokers to stop smoking , but they help patients to modify their diet and total cholesterol concentration . The public health importance of this dietary change depends on whether it is sustained Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews PURPOSE We present psychometric properties of 9 health and psychosocial measures in a sample of hospitalized women with cardiovascular disease . This information will be useful to others needing to make choices about selection of health and psychosocial measurements in women smokers . METHODS Psychometric properties were examined using baseline measures from a cross-sectional study , nested within a r and omized clinic trial , Women 's Initiative for Non-Smoking . Women smokers hospitalized with cardiovascular disease were recruited from 10 hospitals in the San Francisco Bay Area . Measures included the perceived stress scale , a depression screener , self-efficacy , the sense of mastery scale , and measures of health-related quality of life from the Medical Outcomes Study . RESULTS The sample of 277 women smokers ranged in age from 34 to 86 years ( mean = 61 + /- 10.1 ) . Studies of variability , including floor/ceiling effects , skewness , range , mean , and SD , indicated that most measures had sufficient variability to be predictive and detect both positive and negative changes over time . Internal-consistency reliabilities ranged from 0.63 to 0.86 . Preliminary evidence of construct validity was found , with most hypotheses being confirmed . CONCLUSIONS The battery of tests included in the Women 's Initiative for Non-Smoking trial may be useful in identifying women at high risk of relapse and in detecting short-term quality -of-life outcomes . The measures generally performed well and show promise for advancing our underst and ing of the process of successful smoking cessation in this population . SUMMARY Psychometric properties of the perceived stress scale , a depression screener , self-efficacy for quitting smoking , the sense of mastery scale , and measures of health-related quality of life from the Medical Outcomes Study in 277 women smokers hospitalized with cardiovascular disease were examined . The measures generally performed well and show promise for advancing our underst and ing of smokers in this population OBJECTIVE To evaluate two nursing approaches to promoting smoking cessation during initial antenatal visits . DESIGN Experimental , with assignment to interventions using a r and om , alternate-day strategy and blind assessment of smoking at baseline , 1 month postintervention , 36 weeks ' gestation , and 6 weeks postpartum . SETTING / PARTICIPANTS 224 daily smokers , fewer than 31 weeks gestation , during first prenatal visit , at a teaching hospital antenatal clinic . INTERVENTIONS An evening class providing guidance on a self-help program for 2 hours on a group basis or 20 minutes on an individual basis during the prenatal appointment . MAIN OUTCOME MEASURE Smoking cessation , confirmed by urinary cotinine levels . RESULTS All women assigned to the referral intervention received a referral , but none attended the classes . In contrast , 93 % assigned to the immediate intervention received the intervention . The group receiving immediate intervention had two to three times higher rates of cessation at all follow-up periods , with significant differences at the 1-month follow-up . There were certain similarities between the groups . CONCLUSION Cessation interventions should be administered during the first prenatal visit A nurse rehabilitator , supplementing routine physician/nursing coronary care unit ( CCU ) care , was found to be effective in increasing the return to work rate ( p < .05 ) and decreasing smoking ( p < .05 ) in a r and omized trial of 102 patients with acute myocardial infa rct ion ( MI ) . These outcomes were thought to be due to the nurse rehabilitator 's efforts in increasing patient knowledge of heart disease ( p < .01 ) and individual counseling ABSTRACT This study investigated the effects of Web-based multiple computer tailoring and counseling by a practice nurse ( MTC ) compared with computer tailoring without counseling ( MT ) and usual care ( UC ) on smoking cessation rates , via a r and omized controlled trial with 414 Dutch adult smokers , recruited by 91 practice nurses from May 2009 to June 2010 . Logistic multilevel regression analyses were conducted with 24-hour point prevalence , 7-day point prevalence , and prolonged abstinence after 6 and 12 months as dependent variables and experimental condition as the independent variable . After 6 and 12 months , 38 % and 56 % of respondents were followed up , respectively . At both follow-ups , no main effects of the interventions could be identified when comparing them with care as usual and with each other — neither in analyses using available data nor in analyses using a negative scenario in which respondents lost to follow-up were considered to still be smoking . A Web-based multiple computer-tailored smoking cessation program combined with a single face-to-face counseling session by a practice nurse may not be more effective than this computer-tailored program alone or than usual smoking cessation care in the general practice setting . Yet before concluding that the addition of counseling to Web-based computer tailoring can not be successful , more research needs to be conducted to identify the optimal number of counseling sessions to be combined with the Web-based program and to how to best attune the two modalities AIMS To evaluate the effectiveness of a 6-month , partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease . BACKGROUND Self-management is a widely valued concept used to address contemporary issues of chronic health problems . Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive . DESIGN Pragmatic r and omized control trial . METHODS Patients , 45 - 65 years old , with mild and moderate chronic obstructive pulmonary disease were invited with a family member . Experimental group ( n = 48 ) participated in a 6-month , partnership-based self-management programme consisting of : ( a ) three to four conversations between nurse and patient-family member ; ( b ) 6 months of smoking cessation ; and ( c ) interdisciplinary team-patient-family member group meeting . Control group ( n = 52 ) received usual care . Data were collected at months zero , six and 12 . The trial lasted from June 2009-March 2013 . RESULTS Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group . Patients in the experimental group did not have better health-related quality of life , less anxiety or depression , increased physical activity , fewer exacerbations or better smoking status than patients in the control group . Patients in both groups found participation in the research useful and important . CONCLUSION The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles , activities and interests for young patients with the disease in its early stages . High satisfaction in control group , low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme Background The diabetes of many patients is managed in general practice ; healthcare providers aim to promote healthful behaviors , such as healthful diet , adequate physical activity , and smoking cessation . These measures may decrease insulin resistance , improve glycemic control , lipid abnormalities , and hypertension . They may also prevent cardiovascular disease and complications of diabetes . However , professionals do not adhere optimally to guidelines for lifestyle counseling . Motivational interviewing to change the lifestyle of patients with type 2 diabetes is intended to improve diabetes care in accordance with the national guidelines for lifestyle counseling . Primary care nurses will be trained in motivational interviewing embedded in structured care in general practice . The aim of this paper is to describe the design and methods of a study evaluating the effects of the nurses ' training on patient outcomes . Methods / Design A cluster , r and omized , controlled trial involving 70 general practice s ( 35 practice s in the intervention arm and 35 in the control arm ) starting in March 2007 . A total of 700 patients with type 2 diabetes will be recruited . The patients in the intervention arm will receive care from the primary care nurse , who will receive training in an implementation strategy with motivational interviewing as the core component . Other components of this strategy will be adaptation of the diabetes protocol to local circumstances , introduction of a social map for lifestyle support , and educational and supportive tools for sustaining motivational interviewing . The control arm will be encouraged to maintain usual care . The effect measures will be the care process , metabolic parameters ( glycosylated hemoglobin , blood pressure and lipids ) , lifestyle ( diet , physical activity , smoking , and alcohol ) , health-related quality of life , and patients ' willingness to change behaviors . The measurements will take place at baseline and after 14 months . Discussion Applying motivational interviewing for patients with diabetes in primary care has been studied , but to our knowledge , no other study has yet evaluated the implementation and sustainability of motivating and involving patients in day-to-day diabetes care in general practice . If this intervention proves to be effective and cost-effective , large-scale implementation of this nurse-oriented intervention will be considered and anticipated . Trial registration Current Controlled Trials IS RCT N68707773 |
11,271 | 26,456,456 | Conclusions MTHFR C677 T might be correlated with the tumor response to p RCT . | Background Preoperative chemoradiotherapy ( p RCT ) followed by surgery has been widely practice d in locally advanced rectal cancer , esophageal cancer , gastric cancer and other cancers .
However , the therapy also exerts some severe adverse effects and some of the patients show poor or no response .
It is very important to develop biomarkers ( e.g. , gene polymorphisms ) to identify patients who have a higher likelihood of responding to p RCT .
Recently , a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase ( MTHFR ) and epidermal growth factor receptor ( EGFR ) genes with the tumor response to p RCT ; however , the results were inconsistent and inconclusive . | Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy ( p RCT ) , but the response is not uniform . Identification of patients with higher likelihood of responding to p RCT is clinical ly relevant , as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects . To highlight predictive biomarkers of response to p RCT , a systematic search of PubMed was conducted with a combination of the following terms : “ rectal ” , “ predictive ” , “ radiochemotherapy ” , “ neoadjuvant ” , “ response ” and “ biomarkers ” . Genetic polymorphisms in epithelial growth factor receptor ( EGFR ) and thymidylate synthase ( TS ) genes , the expression of several markers , such as EGFR , bcl-2/bax and cyclooxygenase (COX)-2 , and circulating biomarkers , such as serum carcinoembryonic antigen ( CEA ) level , are promising as predictor markers , but need to be further evaluated . The majority of the studies did not support the predictive value of p53 , while the values of Ki-67 , TS and p21 is still controversial . Gene expression profiles of thous and s of genes using microarrays , microRNA studies and the search for new circulating molecules , such as human telomerase reverse transcriptase mRNA and cell-free DNA , are providing interesting results that might lead to the identification of new useful biomarkers . Evaluation of biomarkers in larger , prospect i ve trials are required to guide therapeutic strategies Objective : To prospect ively describe patient-reported outcomes ( PROs ) after preoperative chemoradiotherapy ( pCRT ) for rectal cancer . Background : Little evidence is available on PROs after pCRT for rectal cancer . Patients and Methods : Patients with rectal cancer , c and i date s to receive pCRT , were enrolled in a multicenter prospect i ve observational trial . Health-related quality of life was assessed using the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 and its colorectal cancer module ( QLQ-CR38 ) , and fecal incontinence and bowel function were evaluated using the fecal incontinence score question naire and a set of ad hoc questions . Question naires were filled out before CRT ( t0 ) , 2 to 3 weeks after completion of CRT ( t1 ) , and at 6 ( t2 ) and 12 months ( t3 ) after surgery . Primary analysis of selected scales included : global quality of life , physical functioning , social functioning , fatigue , body image , future prospect i ve , and gender-related sexual problems . Results : Of 149 eligible patients , question naires were completed in 100 % , 95 % , 88 % and 77 % of cases at t0 , t1 , t2 , and t3 , respectively . At t3 , 78 % of patients reported stool fractionation and 72 % sensation of incomplete defecation . Only 14 % of patients had optimal continence . Physical/social functioning , fatigue , and body image showed a decrease just after pCRT and returned to baseline levels at 1 year after treatment . Global quality of life was stable over time . Male sexual problems were greatly impaired throughout the study period ( P < 0.001 ) with major clinical ly meaningful changes between baseline and 1 year after treatment . Conclusions : These findings add to the body of evidence available regarding pCRT and help clinicians to make more informed treatment decisions AIMS The identification of predictive markers of response to chemoradiotherapy treatment remains a promising approach for patient management in order to obtain the best response with minor side effects . Initially , we investigated whether the analysis of several markers previously studied and others not yet evaluated could predict response to 5-fluorouracil- and capecitabine-based neoadjuvant treatment in locally advanced rectal cancer . METHODS & MATERIAL S We studied germline and tumoral sample s of 65 stage II/III rectal patients . A panel of pharmacogenetic markers was genotyped in paired peripheral blood sample s and rectal cancer tumors . RESULTS Our results seem to confirm the previously described association of thymidylate synthase and the prediction of chemoradiotherapy response in rectal cancer . However , it failed to confirm the clinical utility proposed for XRCC1 , ERCC1 , ERCC2 , MTHFR and EGFR polymorphisms in blood/germline sample s. Subsequently , with the aim of improving prediction of individual response and assessing the role of studied polymorphisms in response to treatment , we determined if changes in tumor response to these markers could predict clinical outcome . We found a high degree of changes between germline and tumor sample s , mainly somatic mutations without microsatellite instability , and a minor frequency of loss-of-heterozygosity events . In tumoral sample s , XRCC1 appeared to be significantly associated ( p = 0.006 ) with downstaging of the tumor ( odds ratio : 7.93 ; 95 % CI : 1.03 - 60.83 ) , but the increasing of TYMS low-expression alleles contradict the previous results observed in germline sample s. CONCLUSION The detection of somatic mutations in rectal cancer tumors led us to re-evaluate the utility of the tests performed in blood sample s for these polymorphisms in rectal cancer . Furthermore , studies aim ed at assessing the influence of pharmacogenetic markers in treatment response performed in blood sample s should take into account the particular pattern of hypermutability present in each tumor type . We hypothesize that different patterns of hypermutability present in each tumor type would be related to the different results in association studies related to response to the treatment PURPOSE We compared the combined radiation therapy ( RT ) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT , fluorouracil ( 5-FU ) , and high-dose leucovorin ( LV ) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer . PATIENTS AND METHODS Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU . Patients with resectable disease received identical doses , techniques , and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively . On day 1 , patients received LV and 5-FU times one cycle . RT began on day 8 . A second cycle of LV and 5-FU was given concurrently with the fourth week of RT . RESULTS Although more patients ( 75 % v 32 % ; P = .02 ) received the higher dose level of 5-FU ( 250 mg/m2 ) , significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy ( 13 % v 48 % ; P = .045 ) . There was no grade 3 to 4 myelosuppression in either group . The two grade 3 toxicities in the preoperative group were gastrointestinal . The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary ; four patients had a grade 4 toxicity . CONCLUSION Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant r and omized trials , future adjuvant trials should explore the preoperative approach The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma ( cT3 - 4 cN0 - 1 cM0 ) after multimodal treatment ( radiochemotherapy±surgical resection ) , and the presence of genetic polymorphisms in genes involved in folate metabolism . In total , 68 patients who took part in a prospect i ve multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy , optionally followed by surgery . DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes ( MTHFR C677 T , MTR A2756 G , TS t and em repeat polymorphism ) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy . The genotypes were correlated with tumour response to polychemotherapy , radiochemotherapy and with overall survival . Tumours with the MTR wild-type genotype ( 2756AA ) showed a median survival time of 16 months , whereas tumours with an MTR variant genotype ( 2756AG/2756GG ) showed a median survival time of 42 months ( P=0.0463 ) . No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene . Among tumours treated with radiochemotherapy and subsequent resection , MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype ( P=0.0442 ) . In contrast , no significant relationship between clinical ly determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed . In conclusion , pretherapeutic determination of the MTR A2756 G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas . Determination of MTHFR C677 T and TS t and em repeat polymorphism has no predictive value 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 Objective : To identify a biomarker profile associated with tumor response to chemoradiation ( CRT ) in locally advanced rectal cancer . Background : Rectal cancer response to neoadjuvant CRT is variable . Whereas some patients have a minimal response , others achieve a pathologic complete response ( pCR ) and have no viable cancer cells in their surgical specimens . Identifying biomarkers of response will help select patients more likely to benefit from CRT . Methods : This study includes 132 patients with locally advanced rectal cancer treated with neoadjuvant CRT followed by surgery . Tumor DNA from pretreatment tumor biopsies and control DNA from paired normal surgical specimens was screened for mutations and polymorphisms in 23 genes . Genetic biomarkers were correlated with tumor response to CRT ( pCR vs non-pCR ) , and the association of single or combined biomarkers with tumor response was determined . Results : Thirty-three of 132 ( 25 % ) patients achieved a pCR and 99 ( 75 % ) patients had non-pCR . Three individual markers were associated with non-pCR ; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutation ( P = 0.0145 ) , cyclin D1 G870A ( AA ) polymorphism ( P = 0.0138 ) , and methylenetetrahydrofolate reductase ( NAD(P)H ) C677 T ( TT ) polymorphism ( P = 0.0120 ) . Analysis of biomarker combinations revealed that none of the 27 patients with both tumor protein p53 ( p53 ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations had a pCR . Further , in patients with both p53 and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations or the cyclin D1 G870A ( AA ) polymorphism or the methylenetetrahydrofolate reductase ( NAD(P)H ) C677 T ( TT ) polymorphism ( n = 52 ) the association with non-pCR was further strengthened ; 51 of 52 ( 98 % ) of patients were non-pCR . These biomarker combinations had a validity of more than 70 % and a positive predictive value of 97 % to 100 % , predicting that patients harboring these mutation/polymorphism profiles will not achieve a pCR . Conclusions : A specific biomarker profile is strongly associated with non-pCR to CRT and could be used to select optimal oncologic therapy in rectal cancer patients . Clinical Trials.org Identifier : NCT00335816 |
11,272 | 28,266,606 | However , for the polymorphisms not being associated following meta- analysis could still be associated if larger cohorts were used , and studies of other polymorphisms are necessary in large cohorts and a rigorous way , which may provide more accurate results for the effect of the gene polymorphisms on the MTX response | Methotrexate ( MTX ) is widely used and considered a first-line disease modifying anti-rheumatic drug ( DMARD ) for the treatment of rheumatoid arthritis ( RA ) .
Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients , although inconsistent results have been reported . | Methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms have been reported to be associated with response to methotrexate ( MTX ) in certain population s of patients with rheumatoid arthritis ( RA ) . This study aims at investigating any relationship of two single nucleotide polymorphisms ( SNPs ) in MTHFR gene , C677 T and A1298C with response to therapy with MTX in Pakistani RA patients . Allelic frequencies of the two polymorphisms ( C677 T and A1298C ) were determined in 67 RA patients ( 9 males and 58 females ; mean age 42.87 ± 13.5 years ) who had previously participated in a prospect i ve clinical trial . Fifty-one patients had received MTX and were followed up for response up to 6 months . Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP , while fasting concentration of plasma homocysteine was determined using a kit method . Twenty-eight patients were found to be " good responders " , while twenty-three were " poor responders " . MTHFR 1298C and MTHFR 677 T alleles ' frequencies in " good responders " were not different from frequencies in " poor responders " ( 0.574 vs. 0.521 ; p=0.6 and 0.197 vs. 0.196 ; p=0.75 , respectively ) . Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi ( 13.1 ± 6.7 µmol/l vs. 11.4 ± 5.3 µmol/l ; p<0.001 ) . MTHFR C677 T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients INTRODUCTION Methotrexate ( MTX ) , widely used in the treatment of rheumatoid arthritis ( RA ) , inhibits dihydrofolate reductase and folate-dependent enzymes . Methylenetetrahydrofolate reductase ( MTHFR ) is involved in folate metabolism and has been shown to be polymorphic , affecting the enzyme activity . METHODS To examine the association between 677C > T and 1298A > C MTHFR polymorphisms and MTX efficacy in the treatment of RA , a total of 174 RA patients , treated with MTX plus methylprednisone 4 mg and folic acid 5 mg were analyzed . RESULTS In univariate regression analysis model , the MTHFR 677 T allele was associated with significantly higher frequency of remission , whereas in the case of the 1298C allele , a tendency for higher remission rate was observed . In multivariate regression analysis , the presence of both 677 T and 1298C alleles was associated with an increased frequency of remission . CONCLUSION The results of our study suggest that the MTHFR 677 T and 1298C alleles may be associated with an increased rate of RA remission in patients treated with MTX receiving high doses of folic acid supplementation Methotrexate ( MTX ) exhibits large inter-individual and inter-ethnic differences in the dose required for its anti-rheumatic effect . To maintain low disease activity , patients may require increased MTX doses or co-administration of biologic disease-modifying anti-rheumatic drugs ( bDMARDs ) . The availability of a marker predicting the effect of MTX will make it possible to increase the MTX dose and prescribe bDMARDs to patients at an early stage . To establish individualized medication for rheumatoid arthritis ( RA ) , we investigated genetic polymorphisms of the folate pathway in Japanese RA patients . Eighty-nine patients were treated with MTX alone ( MTX group ) . MTX and bDMARDs were co-administered to 81 patients because of insufficient MTX efficacy ( MTX + bDMARDs group ) ; an equally stable therapeutic effect was achieved in both groups . Polymorphism analyses using bDMARD co-treatment as the objective variable revealed a significant association between age and the G80A polymorphism of the reduced folate carrier 1 gene ( RFC1 ) as an explanatory variable . Compared to patients with the A allele , patients with the G allele may have less intracellular MTX uptake and , therefore , poor efficacy ; a greater number of them were found to be bDMARD concomitant cases . The results of this study suggest that the RFC1 G80A polymorphism may be a useful marker for predicting MTX efficacy in Japanese patients with RA |
11,273 | 28,703,496 | This systematic review shows that ultrasound is a reliable and valid tool for the assessment of muscle size in older adults . | This review evaluates the reliability and validity of ultrasound to quantify muscles in older adults . | Background Measuring the strength of individual foot muscles is very challenging ; however , measuring muscle morphology has been shown to be associated with strength . A reliable method of assessing foot muscle atrophy and hypertrophy would therefore be beneficial to research ers and clinicians . Thus , the aim of this study was to evaluate the test-retest intra-observer reliability of ultrasound to measure the morphology of the primary toe flexor muscles . Method The abductor hallucis , flexor hallucis brevis , flexor digitorum brevis , quadratus plantae and abductor digiti minimi muscles in the foot , and the flexor digitorum longus and flexor hallucis longus muscles in the shank were assessed in five males and five females ( mean age = 32.1 ± 10.1 years ) . Muscles were imaged using a GE Venue 40 ultrasound ( 6 - 9 or 7.6 - 10.7 MHz transducer ) in a r and om order , and on two occasions 1 - 6 days apart . Muscle thickness and cross-sectional area were measured using Image J software with the assessor blinded to muscle and day of scan . Intraclass correlation coefficients ( ICC ) and limits of agreement were calculated to assess day-to-day repeatability of the measurements . Results The method was found to have good reliability ( ICC = 0.89 - 0.99 ) with limits of agreement between 8 - 28 % of the relative muscle size . Conclusion The protocol described in this paper showed that ultrasound is a reliable method to measure morphology of the toe flexor muscles . The portability and advantages of ultrasound make it a useful tool for clinical and research setting Abstract Reliability refers to the reproducibility of values of a test , assay or other measurement in repeated trials on the same individuals . Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical setting s. The main measures of reliability are within-subject r and om variation , systematic change in the mean , and retest correlation . A simple , adaptable form of within-subject variation is the typical ( st and ard ) error of measurement : the st and ard deviation of an individual ’s repeated measurements . For many measurements in sports medicine and science , the typical error is best expressed as a coefficient of variation ( percentage of the mean ) . A biased , more limited form of within-subject variation is the limits of agreement : the 95 % likely range of change of an individual ’s measurements between 2 trials . Systematic changes in the mean of a measure between consecutive trials represent such effects as learning , motivation or fatigue ; these changes need to be eliminated from estimates of within-subject variation . Retest correlation is difficult to interpret , mainly because its value is sensitive to the heterogeneity of the sample of participants . Uses of reliability include decision-making when monitoring individuals , comparison of tests or equipment , estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment . Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials . Studies aim ed at assessing variation in reliability between tests or equipment require complex design s and analyses that research ers seldom perform correctly . A wider underst and ing of reliability and adoption of the typical error as the st and ard measure of reliability would improve the assessment of tests and equipment in our disciplines This prospect i ve , blinded study investigates the test retest reliability of measures of muscle thickness made by one sonographer across two cohort groups ( n = 29 ) of people hospitalised with acute stroke . Reliability was assessed in cohort one ( n = 14 ) for measurements made bilaterally at the anterior and posterior upper arms , the anterior and posterior thighs ( total of eight measurements ) and in cohort two ( n = 15 ) , for measurements made bilaterally at the lateral forearms , the anterior abdominal wall and the anterior and lower legs ( total of eight measurements ) . Reliability estimates varied between measurement sites ; intraclass correlation coefficients ( ICCs ) ranged from -0.26 ( lateral forearm , paretic side ) to 0.95 ( anterior thigh , nonparetic side ) , percent mean differences ranged from 0.42 % ( posterior upper arm , nonparetic side ) to 14.68 % ( anterior lower limb , nonparetic side ) and method error ranged from 1.08 ( abdomen , nonparetic side ) to 9.69 mm ( posterior lower limb , nonparetic side ) . Only four measurement sites ( anterior upper arm , posterior upper arm , abdomen and anterior thigh ) were within the acceptable ranges ( ICC 0.60 to 1.00 , mean percent difference range 0%-5 % and method error range 0 - 5 mm ) and considered reliable to use for measures of muscle thickness in people hospitalised with acute stroke The present study was performed to develop regression-based prediction equations for skeletal muscle ( SM ) mass by ultrasound and to investigate the validity of these equations in Japanese adults . Seventy-two Japanese men ( n=38 ) and women ( n=34 ) aged 18–61 years participated in this study and were r and omly separated into two groups : the model development group ( n=48 ) and the validation group ( n=24 ) . The total and regional SM mass were measured using magnetic resonance imaging ( MRI ) 1.5 T-scanners with spin-echo sequence . Contiguous transverse images ( about 150 slices ) with a slice thickness of 1 cm were obtained from the first cervical vertebra to the ankle joints . The volume of SM was calculated from the summation of digitized cross-sectional area . The SM volume was converted into mass units ( kg ) by an assumed SM density of 1.04 kg l−1 . The muscle thickness ( MTH ) was measured by B-mode ultrasound ( 5 MHz scanning head ) at nine sites on the anatomical SM belly . Strong correlations were observed between the site-matched SM mass ( total , arm , trunk body , thigh , and lower leg ) by MRI measurement and the MTH × height ( in m ) in the model development group ( r=0.83–0.96 in men , r=0.53–0.91 in women , P<0.05 ) . When the SM mass prediction equations were applied to the validation group , significant correlations were also observed between the MRI-measured and predicted SM mass ( P<0.05 ) . The predicted total SM mass for the validation group was 19.6 ( 6.5 ) kg and was not significantly different from the MRI-measured SM mass of 20.2 ( 6.5 ) kg . Bl and –Altman analysis did not indicate a bias in prediction of the total SM mass for the validation group ( r=0.00 , NS ) . These results suggested that ultrasound-derived prediction equations are a valid method to predict SM mass and an alternative to MRI measurement in healthy Japanese adults Abstract . This study aim ed to investigate the suitability of using ultrasonograph muscle thickness ( MT ) measurements to estimate the muscle volume ( MV ) of the quadriceps femoris as an alternative approach to magnetic resonance imaging ( MRI ) . The subjects were 46 men aged from 20 to 70 years who were r and omly allocated to either a validation or a cross-validation group . In the validation group , multiple and simple regression equations , which used a set of MT values determined at mid-thigh and thigh length ( l ) and the product of π , (MT/2)2 , and l [ π·(MT/2)2·l ] , respectively , as independent variables , were derived to estimate the MV measured by MRI . Because the two equations were cross-vali date d , the data from the two groups were pooled to generate the final prediction equations : MV (cm3)=(MT × 311.732)+(l × 53.346 ) –2058.529 as the multiple regression equation and MV (cm3)=[π·(MT/2)2·l] × 1.1176 + 663.040 as the simple regression equation . In the multiple regression equation , MT explained 75 % of the variation in the MV measured by MRI . The r2 and the st and ard error of the estimate ( SEE ) of the equations were 0.824 and 175.6 cm3 ( 10.6 % ) , respectively , for the multiple regression equation and 0.829 and 173.7 cm3 ( 10.5 % ) , respectively , for the simple regression equation . Thus , the present results indicate that ultrasonograph MT measurements at mid-thigh are useful for estimating the MV of knee extensors . However , the observed SEE values suggest that the prediction equation obtained in this study may be limited to population studies rather than individual assessment s in longitudinal studies BACKGROUND AND AIMS sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals . We evaluated the impact of sarcopenia on the risk of all-cause death in a population of frail older persons living in community . METHODS we analysed data from the Aging and Longevity Study , a prospect i ve cohort study that collected data on all subjects aged 80 years and older residing in the Sirente geographic area ( n = 364 ) . The present analysis was conducted among those subjects who were between 80 and 85 years of age at the time of the baseline assessment ( n = 197 ) . The main outcome measure was all-cause mortality over 7-year follow-up . According to the European Working Group on Sarcopenia in Older People ( EWGSOP ) criteria , the diagnosis of sarcopenia required the documentation of low muscle mass and the documentation of either low muscle strength or low physical performance . Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95 % confidence intervals of death by the presence of sarcopenia . RESULTS using the EWGSOP-suggested criteria , 43 subjects with sarcopenia ( 21.8 % ) were identified . During the 7-year follow-up , 29 ( 67.4 % ) participants died among subjects with sarcopenia compared with 63 subjects ( 41.2 % ) without sarcopenia ( P < 0.001 ) . After adjusting for potential confounders including age , gender , education , activities of daily living ( ADL ) impairment , body mass index , hypertension , congestive heart failure , chronic obstructive pulmonary disease , number of diseases , TNF-α , participants with sarcopenia had a higher risk of death for all causes compared with non-sarcopenic subjects ( HR : 2.32 , 95 % CI : 1.01 - 5.43 ) . CONCLUSIONS our results obtained from a representative sample of very old and frail subjects show that sarcopenia is associated with mortality , independently of age and other clinical and functional variables The increase of elderly in our society requires simple tools for quantification of sarcopenia in inpatient and outpatient setting s. The aim of this study was to compare parameters determined with musculoskeletal ultrasound ( M-US ) with muscle strength in young and elderly patients . In this prospect i ve , r and omised and observer blind study , 26 young ( 24.2 ± 3.7 years ) and 26 old ( age 67.8 ± 4.8 years ) patients were included . Muscle thickness , pennation angle and echogenicity of all muscles of musculus quadriceps were measured by M-US and correlated with isometric maximum voluntary contraction force ( MVC ) of musculus quadriceps . Reproducibility of M-US measurements as well as simple and multiple regression models were calculated . Of all measured M-US variables the highest reproducibility was found for measurements of thickness ( intraclass correlation coefficients , 85–97 % ) . Simple regression analysis showed a highly significant correlation of thickness measurements of all muscles of musculus quadriceps with MVC in the elderly and in the young . Multiple regression analysis revealed that thickness of musculus vastus medialis had the best correlation with MVC in the elderly . This study showed that measurement of muscle thickness , especially of musculus vastus medialis , by M-US is a reliable , bedside method for monitoring the extent of sarcopenia |
11,274 | 27,274,105 | Clear evidence was found that RS had positive effects on many health-related indices and variables , including VO2max ( gains of 7 - 16 % ) , blood pressure ( reductions of 6 - 13 mmHg ) , body composition ( decreased fat mass and improved indices of bone health ) , and metabolic and cardiac function .
These positive effects were observed in both healthy individuals and clinical patients , irrespective of age or sex .
Regular RS training leads to significant cardiovascular and muscular adaptations and gains of health both in sedentary individuals and clinical patients at all ages , suggesting that RS is a potentially highly motivational method to enhance population health | Recreational soccer ( RS ) is becoming a popular alternative to the classical continuous exercise mode used for the improvement of cardiovascular and metabolic fitness in untrained people .
The objective of this paper was to conduct a detailed systematic review of the literature , identifying the physiological responses to RS and the training effects of RS on aerobic fitness and health in untrained healthy individuals and clinical patients . | The present study examined the cardiovascular health effects of 16 weeks of recreational football training in untrained premenopausal women in comparison with continuous running training . Fifty healthy women were matched and r and omized to a football ( FG , n=25 ) or a running ( RG , n=25 ) group and compared with a control group with no physical training ( CO , n=15 ) . Training was performed for 1 h twice a week . After 16 weeks , systolic and diastolic blood pressure was reduced ( P<0.05 ) in FG ( 7+/-2 and 4+/-1 mmHg ) and systolic blood pressure was lowered ( P<0.05 ) in RG ( 6+/-2 mmHg ) . After 16 weeks , resting heart rate was lowered ( P<0.05 ) by 5+/-1 bpm both in FG and RG , and maximal oxygen uptake was elevated ( P<0.05 ) by 15 % in FG and by 10 % in RG ( 5.0+/-0.7 and 3.6+/-0.6 mL/min/kg , respectively ) . Total fat mass decreased ( P<0.05 ) by 1.4+/-0.3 kg in FG and by 1.1+/-0.3 kg in RG . After 16 weeks , pulse pressure wave augmentation index ( -0.9+/-2.5 vs 4.2+/-2.4 % ) , skeletal muscle capillarization ( 2.44+/-0.15 vs 2.07+/-0.05 cap/fib ) and low-density lipoprotein/high-density lipoprotein cholesterol ratio were improved ( P<0.05 ) in FG , but not altered in RG . No changes were observed in CO . In conclusion , regular recreational football training has significant favorable effects on the cardiovascular risk profile in untrained premenopausal women and is at the least as efficient as continuous running The present study investigated whether football has favorable effects in the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men . Twenty-five untrained males aged 31 - 54 year with mild-to-moderate hypertension were r and omized to a football training group ( FTG , two 1-h sessions per week ) and a control group receiving physician-guided traditional recommendations on cardiovascular risk factor modification ( doctoral advice group , DAG ) . After 3 months , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were lowered ( P<0.05 ) by 12 + /- 3 and 7 + /- 1 mmHg in FTG , respectively , whereas no significant changes were observed for DAG , with the 3 months values being lower ( P<0.05 ) in FTG than DAG ( SBP : 138 + /- 2 vs 148 + /- 2 mmHg ; DBP : 84 + /- 2 vs 92 + /- 2 mmHg ) . The resting heart rate was lowered ( P<0.05 ) by 12 + /- 2 b.p.m . in FTG after 3 months ( 67 + /- 3 vs 79 + /- 3 b.p.m . ) , whereas no change was observed for DAG . After 3 months , FTG had higher ( P<0.05 ) VO(2max ) ( 8 + /- 2 % ; 35.0 + /- 1.6 vs 32.5 + /- 1.3 mL/min/kg ) and lower ( P<0.05 ) fat mass ( 1.7 + /- 0.6 kg ) , whereas no change was observed for DAG . In conclusion , football training is an attractive non-pharmacological supplement to the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men The effects of 16 weeks of football or strength training on performance and functional ability were investigated in 26 ( 68.2 ± 3.2 years ) untrained men r and omized into a football ( FG ; n = 9 ) , a strength training ( ST ; n = 9 ) , or a control group ( CO ; n = 8) . FG and ST trained 1.6 ± 0.1 and 1.5 ± 0.1 times per week , respectively , with higher ( P < 0.05 ) average heart rate ( HR ) ( ∼140 vs 100 bpm ) and time > 90%HRmax ( 17 vs 0 % ) in FG than ST , and lower ( P < 0.05 ) peak blood lactate in FG than ST ( 7.2 ± 0.9 vs 10.5 ± 0.6 mmol/L ) . After the intervention period ( IP ) , VO₂ max ( 15 % ; P < 0.001 ) , cycle time to exhaustion ( 7 % ; P < 0.05 ) , and Yo-Yo Intermittent Endurance Level 1 performance ( 43 % ; P < 0.01 ) were improved in FG , but unchanged in ST and CO . HR during walking was 12 % and 10 % lower ( P < 0.05 ) in FG and ST , respectively , after IP . After IP , HR and blood lactate during jogging were 7 % ( P < 0.05 ) and 30 % lower ( P < 0.001 ) in FG , but unchanged in ST and CO . Sit-to-st and performance was improved ( P < 0.01 ) by 29 % in FG and 26 % in ST , but not in CO . In conclusion , football and strength training for old men improves functional ability and physiological response to submaximal exercise , while football additionally elevates maximal aerobic fitness and exhaustive exercise performance The purpose of this study was to determine the effects of recreational soccer ( SOC ) compared to moderate-intensity continuous running ( RUN ) on all health-related physical fitness components in healthy untrained men . Sixty-nine participants were recruited and r and omly assigned to one of three groups , of which sixty-four completed the study : a soccer training group ( SOC ; n = 20 , 34±4 ( means±SD ) years , 78.1±8.3 kg , 179±4 cm ) ; a running group ( RUN ; n = 21 , 32±4 years , 78.0±5.5 kg , 179±7 cm ) ; or a passive control group ( CON ; n = 23 , 30±3 years , 76.6±12.0 kg , 178±8 cm ) . The training intervention lasted 12 weeks and consisted of three 60-min sessions per week . All participants were tested for each of the following physical fitness components : maximal aerobic power , minute ventilation , maximal heart rate , squat jump ( SJ ) , countermovement jump with arm swing ( CMJ ) , sit- and -reach flexibility , and body composition . Over the 12 weeks , VO2max relative to body weight increased more ( p<0.05 ) in SOC ( 24.2 % , ES = 1.20 ) and RUN ( 21.5 % , ES = 1.17 ) than in CON ( -5.0 % , ES = -0.24 ) , partly due to large changes in body mass ( -5.9 , -5.7 and + 2.6 kg , p<0.05 for SOC , RUN and CON , respectively ) . Over the 12 weeks , SJ and CMJ performance increased more ( p<0.05 ) in SOC ( 14.8 and 12.1 % , ES = 1.08 and 0.81 ) than in RUN ( 3.3 and 3.0 % , ES = 0.23 and 0.19 ) and CON ( 0.3 and 0.2 % ) , while flexibility also increased more ( p<0.05 ) in SOC ( 94 % , ES = 0.97 ) than in RUN and CON ( 0–2 % ) . In conclusion , untrained men displayed marked improvements in maximal aerobic power after 12 weeks of soccer training and moderate-intensity running , partly due to large decreases in body mass . Additionally soccer training induced pronounced positive effects on jump performance and flexibility , making soccer an effective broad-spectrum fitness training intervention The study examined the effects of 1 year of football or strength training on cardiovascular function in 65- to 75-year-old men . Twenty-six untrained men ( age : 68.2 ± 3.2 years ) were r and omized to football training ( FTG ; n = 9 ) , strength training ( STG ; n = 9 ) , or control ( CG ; n = 8) . In FTG , left ventricular ( LV ) internal diastolic diameter , end-diastolic volume , and mass index were 8 % , 21 % , and 18 % higher ( P < 0.01 ) , respectively , after 12 months , with no changes in STG and CG . After 12 months , LV ejection fraction was increased ( P < 0.05 ) by 8 % and 5 % in FTG and STG , respectively , and systolic longitudinal two-dimensional strain by 8 % and 6 % , whereas right ventricular systolic function improved ( P < 0.05 ) by 22 % in FTG , but not in STG and CG . In FTG , LV diastolic mitral inflow ( E/A ) ratio and peak early diastolic velocity ( E ' ) improved ( P < 0.05 ) by 25 % and 12 % , respectively , after 12 months , with no changes in STG and CG . In FTG , maximum oxygen uptake was 16 % and 18 % higher ( P < 0.001 ) after 4 and 12 months , respectively , and resting heart rate was 6 and 8 beats per minute lower ( P < 0.001 ) , respectively , with no changes in STG and CG . In conclusion , football training elicited superior cardiovascular effects compared with strength training in elderly untrained men Abstract We investigated the musculoskeletal health profile of elite female football players ( ET ) in comparison to untrained ( UT ) young women subjected to 16 weeks of football training ( 2 × 1 h per week ) . DXA scans , blood sampling , sprint testing and Flamingo postural balance testing were carried out for 27 Danish national team players and 28 untrained women , with eight women being tested after training . At baseline total BMD and BMC were 13 % ( 1.305 ± 0.050 versus 1.159 ± 0.056 g · cm−2 ) and 23 % ( 3047 ± 235 versus 2477 ± 526 g ) higher ( P < 0.001 ) and leg BMD and BMC were 24 and 28 % higher ( P < 0.01 ) in ET than in UT . Resting plasma osteocalcin was 45 % higher in ET than in UT ( 28.8 ± 10.9 versus 19.9 ± 9.9 µg · L−1 , P < 0.05 ) . Total lean body mass was 14 % higher ( 50.4 ± 3.3 versus 44.3 ± 4.0 kg ) in ET compared with UT , with no difference in total body mass . The number of Flamingo test falls was 56–63 % less ( P < 0.01 ) and 30 m sprinting speed was 31 % faster ( P < 0.001 ) in ET than UT . After 16 weeks of football training for UT , lean body mass increased by 1.4 ± 0.5 kg and the number of left leg falls decreased by 29 % ( P < 0.05 ) . No significant changes occurred in BMD or BMC , but plasma osteocalcin increased ( P < 0.05 ) by 37 % . In summary , elite women footballers have an impressive musculoskeletal health profile compared with untrained controls , but short-term football training seems to reduce the risk of falls and increase bone formation The present study examined the cardiac effects of football training and running for inactive pre-menopausal women by st and ard echocardiography and tissue Doppler imaging . Thirty-seven subjects were r and omized to two training groups ( football : FG ; n=19 ; running ; RG ; n=18 ) training 1 h with equal average heart rates twice a week for 16 weeks and compared with a matched inactive control group ( CG ; n=10 ) . During the training period , left ventricular end-diastolic volume increased by 13 % in FG and 11 % in RG ( P<0.05 ) . Left ventricular posterior wall thickness increased in FG from 8.5+/-1.4 to 9.0+/-1.3 mm ( P<0.05 ) . Right ventricle diameter increased by 12 % in FG and 10 % in RG ( P<0.05 ) . Tissue Doppler imaging demonstrated increased left ventricular systolic and diastolic performances in both training groups . Peak systolic velocity increased by 26 % in FG and 17 % in RG ( P<0.05 ) and left ventricular longitudinal displacement increased in both groups by 13 % ( P<0.05 ) . Isovolumetric relaxation time decreased significantly more in FG than in RG ( 26 % vs 14 % , respectively P<0.05 ) . In conclusion , 16 weeks of football and running exercise training induced significant changes of cardiac dimensions and had favorable effects on both left ventricular systolic and diastolic function . These training-induced cardiac adaptations appeared to be more consistent after football training compared with running Abstract The aim of this study was to evaluate the physiological effects of soccer and Zumba among female hospital employees during a 40-week intervention period . Hospital employees ( n = 118 ) were cluster-r and omised to either a soccer group ( n = 41 ) , a Zumba group ( n = 38 ) or a control group ( n = 39 ) . Both training groups were encouraged to perform 1-h training sessions twice a week outside working hours throughout the 40 weeks . Maximal oxygen uptake ( VO2 max ) , blood pressure and body composition were measured and blood sample s collected before and after the intervention period . Using intention-to-treat analyses , the Zumba group improved VO2 max compared to the control group ( 2.2 mL · kg−1 · min−1 , 95 % CI , 0.9 , 3.5 , P = 0.001 ) , with no significant increase in the soccer group ( 1.1 mL · kg−1 · min−1 , 95 % CI , −0.2 , 2.4 , P = 0.08 ) . Both intervention groups reduced total body fat mass and fat percentage compared to the control group ( P < 0.01 ) . In the soccer group , but not the Zumba group , a significant difference in lower limb bone mineral density and bone mineral content was observed in comparison to the control group ( P < 0.01 ) . Furthermore , the soccer group , but not the Zumba group , had increased plasma osteocalcin ( 6.6 µg · L−1 , 95 % CI , 2.2 , 11.0 , P < 0.01 ) and decreased plasma leptin ( −6.6 µg · L−1 , 95 % CI , −12.5 , −0.7 , P < 0.05 ) compared to the control group . The present study suggests that workplace-initiated soccer and Zumba training comprising 1–2 sessions per week outside working hours may promote physiological health among female hospital employees The present study aim ed at analyzing the efficacy of a 6-month football training program compared with a st and ard exercise program on health and fitness parameters in overweight children . The study design was a 6-month , two-arm , parallel-group r and omized trial . Twenty-two overweight children were r and omly assigned to two groups ( age=10.8+/-1.2 years , height=1.56+/-0.08 m , weight= 65.1+/-11.4 kg ) . One group conducted a football training program , and the other group an established st and ard sports program . Both interventions took place three times per week from mid-May to mid-November . Before , after 3 months and after the training period , comprehensive testing was conducted : anthropometric characteristics , cycling ergometry , psychometric monitoring as well as several motor ability tests . Maximal performance capacity increased and submaximal heart rate during cycling ergometry decreased significantly . Several motor skills as well as self-esteem also improved considerably . Body composition and other psychometric variables remained nearly unchanged . No relevant differences were observed between both exercise programs . It can be concluded that a 6-month football training is as efficacious in improving the physical capacity , health-related fitness parameters and self-esteem of overweight children as a st and ard exercise program . These results provide further evidence that playing football has significant health effects Purpose The present study examined the effects of 15 weeks of soccer training and two different swimming training protocol s on bone turnover in sedentary middle-aged women . Methods Eighty-three premenopausal mildly hypertensive women [ age : 45 ± 6 ( ±SD ) years , height : 165 ± 6 cm , weight : 80.0 ± 14.1 kg , body fat : 42.6 ± 5.7 % , systolic blood pressure/diastolic blood pressure : 138 ± 6/85 ± 3 mmHg ] were r and omized into soccer training ( SOC , n = 21 ) , high-intensity intermittent swimming ( HS , n = 21 ) , moderate-intensity swimming ( MS , n = 21 ) intervention groups , and a control group ( C , n = 20 ) . The training groups completed three sessions per week for 15 weeks . DXA scans were performed and resting blood sample s were drawn pre- and post-intervention . Results In SOC , plasma osteocalcin , procollagen type I N propeptide and C-terminal telopeptide increased ( P < 0.05 ) by 37 ± 15 , 52 ± 23 and 42 ± 18 % , respectively , with no changes in MS , HS and C. The intervention-induced increase in SOC was larger ( P < 0.05 ) than in MS , HS and C. In SOC , leg BMC increased ( P < 0.05 ) by 3.1 ± 4.5 % , with a larger increase in SOC than in C. Femoral shaft and trochanter bone mineral density ( BMD ) increased ( P < 0.05 ) by 1.7 ± 1.9 and 2.4 ± 2.9 % , respectively , in SOC , with a greater ( P < 0.05 ) change in SOC than in MS and C , whereas total body and total leg BMD did not change in any of the groups . Conclusion In conclusion , 15 weeks of soccer training with sedentary middle-aged women caused marked increases in bone turnover markers , with concomitant increases in leg bone mass . No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training . Thus , soccer training appears to provide a powerful osteogenic stimulus in middle-aged women Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk , independent of the performance of exercise . We hypothesized that a daily bout of exercise can not compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids . Methodology /Principal Findings Eighteen healthy subjects , age 21±2 year , BMI 22.6±2.6 kgm−2 followed r and omly three physical activity regimes for four days . Participants were instructed to sit 14 hr/day ( sitting regime ) ; to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr ( exercise regime ) ; to substitute 6 hrs sitting with 4 hr walking and 2 hr st and ing ( minimal intensity physical activity ( PA ) regime ) . The sitting and exercise regime had comparable numbers of sitting hours ; the exercise and minimal intensity PA regime had the same daily energy expenditure . PA was assessed continuously by an activity monitor ( ActivPAL ) and a diary . Measurements of insulin sensitivity ( oral glucose tolerance test , OGTT ) and plasma lipids were performed in the fasting state , the morning after the 4 days of each regime . In the sitting regime , daily energy expenditure was about 500 kcal lower than in both other regimes . Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml , respectively . Triglycerides , non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise . Conclusions One hour of daily physical exercise can not compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting . Reducing inactivity by increasing the time spent walking/st and ing is more effective than one hour of physical exercise , when energy expenditure is kept constant We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men . Thirty-one untrained males with mild-to-moderate hypertension were r and omized 2:1 to a football training group ( n = 20 ) and a control group receiving traditional recommendations on healthy lifestyle ( n = 11 ) . Cardiac measures were evaluated by echocardiography . The football group exhibited significant ( P < 0.05 ) changes in cardiac dimensions and function after just 3 months : Left ventricular ( LV ) end-diastolic volume increased from 104 ± 25 to 117 ± 29 mL. LV diastolic function improved measured as E/A ratio ( 1.15 ± 0.32 to 1.54 ± 0.38 ) , early diastolic velocity , E ' ( 11.0 ± 2.5 to 11.9 ± 2.6 cm/s ) , and isovolumetric relaxation time ( 74 ± 13 to 62 ± 13 ms ) . LV systolic function improved measured as longitudinal displacement ( 10.7 ± 2.1 to 12.1 ± 2.3 mm ) . Right ventricular function improved with respect to tricuspid annular plane systolic excursion ( 21.8 ± 3.2 to 24.5 ± 3.7 mm ) . Arterial blood pressure decreased in both groups , but significantly more in the football training group . No significant changes were observed in the control group . In conclusion , short-term football training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension . Furthermore , it may improve longitudinal systolic function of both ventricles . The results suggest that football training has favorable effects on cardiac function in hypertensive men To examine the effects of regular participation in recreational soccer on health profile , 36 healthy untrained Danish men aged 20–43 years were r and omised into a soccer group ( SO ; n = 13 ) , a running group ( RU ; n = 12 ) and a control group ( CO ; n = 11 ) . Training was performed for 1 h two or three times per week for 12 weeks ; at an average heart rate of 82 % ( SEM 2 % ) and 82 % ( 1 % ) of HRmax for SO and RU , respectively . During the 12 week period , maximal oxygen uptake increased ( p<0.05 ) by 13 % ( 3 % ) and 8 % ( 3 % ) in SO and RU , respectively . In SO , systolic and diastolic blood pressure were reduced ( p<0.05 ) from 130 ( 2 ) to 122 ( 2 ) mm Hg and from 77 ( 2 ) to 72 ( 2 ) mm Hg , respectively , after 12 weeks , with similar decreases observed for RU . After the 12 weeks of training , fat mass was 3.0 % ( 2.7 ( 0.6 ) kg ) and 1.8 % ( 1.8 ( 0.4 ) kg ) lower ( p<0.05 ) for SO and RU , respectively . Only SO had an increase in lean body mass ( 1.7 ( 0.4 ) kg , p<0.05 ) , an increase in lower extremity bone mass ( 41 ( 8) g , p<0.05 ) , a decrease in LDL-cholesterol ( 2.7 ( 0.2 ) to 2.3 ( 0.2 ) mmol/l ; p<0.05 ) and an increase ( p<0.05 ) in fat oxidation during running at 9.5 km/h . The number of capillaries per muscle fibre was 23 % ( 4 % ) and 16 % ( 7 % ) higher ( p<0.05 ) in SO and RU , respectively , after 12 weeks . No changes in any of the measured variables were observed for CO . In conclusion , participation in regular recreational soccer training , organised as small-sided drills , has significant beneficial effects on health profile and physical capacity for untrained men , and in some aspects it is superior to frequent moderate-intensity running The present study investigated the cardiac effects of a 10-week football training intervention for school children aged 9 - 10 years using comprehensive transthoracic echocardiography as a part of a larger ongoing study . A total of 97 pupils from four school classes were cluster-r and omized into a control group that maintained their usual activities ( CON ; two classes , n = 51 , 21 boys and 30 girls ) and a football training group that performed an additional 3 × 40 min of small-sided football training per week ( FT ; two classes , n = 46 , 23 boys and 23 girls ) . No baseline differences were observed in age , body composition , or echocardiographic variables between FT and CON . After the 10-week intervention , left ventricular posterior wall diameter was increased in FT compared with CON [ 0.4 ± 0.7 vs -0.1 ± 0.6 ( ± SD ) mm ; P < 0.01 ] as was the interventricular septum thickness ( 0.2 ± 0.7 vs -0.2 ± 0.8 mm ; P < 0.001 ) . Global isovolumetric relaxation time increased more in FT than in CON ( 3.8 ± 10.4 vs -0.9 ± 6.6 ms , P < 0.05 ) while the change in ventricular systolic ejection fraction tended to be higher ( 1.4 ± 8.0 vs -1.1 ± 5.5 % ; P = 0.08 ) . No changes were observed in resting heart rate or blood pressure . In conclusion , a short-term , school-based intervention comprising small-sided football sessions result ed in significant structural and functional cardiac adaptations in pre-adolescent children And rogen deprivation therapy ( ADT ) remains a cornerstone in the management of patients with prostate cancer ( PCa ) despite adverse effects on body composition and functional parameters . We compared the effects of football training with st and ard care in PCa patients managed with ADT ( > 6 months ) . Fifty-seven men aged 67 ( range : 43 - 74 ) were r and omly assigned to a football group ( FG , n = 29 ) or a usual care control group ( CON , n = 28 ) . The primary outcome was change in lean body mass ( LBM ) assessed by dual-energy X-ray absorptiometry scanning . Secondary outcomes included changes in knee-extensor muscle strength ( one repetition maximum ) , fat percentage , and maximal oxygen uptake ( VO2max ) . Mean heart rate during training was 137.7 ( st and ard deviation 13.7 ) bpm or 84.6 (3.9)% HRmax . In FG , LBM increased by 0.5 kg [ 95 % confidence interval ( CI ) 0.1 - 0.9 ; P = 0.02 ] with no change in CON ( mean group difference 0.7 kg ; 95 % CI 0.1 - 1.2 ; P = 0.02 ) . Also , muscle strength increased in FG ( 8.9 kg ; 95 % CI 6.0 - 11.8 ; P < 0.001 ) with no change in CON ( mean group difference 6.7 kg ; 95 % CI 2.8 - 10.7 ; P < 0.001 ) . In FG , VO2max increased ( 1.0 mL/kg/min ; 95 % CI 0.2 - 1.9 ; P = 0.02 ) and fat percentage tended to decrease ( 0.7 % ; 95%CI 1.3 - 0.0 ; P = 0.06 ) , but these changes were not significantly different from CON . In conclusion , football training over 12 weeks improved LBM and muscle strength compared with usual care in men with prostate cancer receiving ADT CONTEXT Recent reports show that obesity and diabetes have increased in the United States in the past decade . OBJECTIVE To estimate the prevalence of obesity , diabetes , and use of weight control strategies among US adults in 2000 . DESIGN , SETTING , AND PARTICIPANTS The Behavioral Risk Factor Surveillance System , a r and om-digit telephone survey conducted in all states in 2000 , with 184 450 adults aged 18 years or older . MAIN OUTCOME MEASURES Body mass index ( BMI ) , calculated from self-reported weight and height ; self-reported diabetes ; prevalence of weight loss or maintenance attempts ; and weight control strategies used . RESULTS In 2000 , the prevalence of obesity ( BMI > /=30 kg/m(2 ) ) was 19.8 % , the prevalence of diabetes was 7.3 % , and the prevalence of both combined was 2.9 % . Mississippi had the highest rates of obesity ( 24.3 % ) and of diabetes ( 8.8 % ) ; Colorado had the lowest rate of obesity ( 13.8 % ) ; and Alaska had the lowest rate of diabetes ( 4.4 % ) . Twenty-seven percent of US adults did not engage in any physical activity , and another 28.2 % were not regularly active . Only 24.4 % of US adults consumed fruits and vegetables 5 or more times daily . Among obese participants who had had a routine checkup during the past year , 42.8 % had been advised by a health care professional to lose weight . Among participants trying to lose or maintain weight , 17.5 % were following recommendations to eat fewer calories and increase physical activity to more than 150 min/wk . CONCLUSIONS The prevalence of obesity and diabetes continues to increase among US adults . Interventions are needed to improve physical activity and diet in communities nationwide INTRODUCTION The present study investigated the fitness and health effects of medium-term soccer training for untrained hypertensive middle-age men . METHODS Thirty-three untrained males ( 31 - 54 yr ) with mild-to-moderate hypertension were r and omized 2:1 to a soccer training group ( STG , two 1-h sessions per week , n = 22 , 68 % on medication ) and a doctor advice group receiving traditional physician-guided recommendations on cardiovascular risk factor modification ( DAG , n = 11 , 73 % on medication ) . Two-way repeated- measures ANOVA time-group statistics was applied . RESULTS During soccer training , average HR was 155 ± 9 bpm or 85 % ± 7 % HRmax . In STG , systolic and diastolic blood pressures decreased ( P < 0.01 ) over 6 months from 151 ± 10 to 139 ± 10 mm Hg and from 92 ± 7 to 84 ± 6 mm Hg , respectively , with smaller ( P < 0.05 ) decreases in DAG ( from 153 ± 8 to 145 ± 8 mm Hg and from 96 ± 6 to 93 ± 6 mm Hg , respectively ) . In STG , V˙O2max increased ( P < 0.01 ) from 32.6 ± 4.9 to 35.4 ± 6.6 mL·min-1·kg-1 and relative V˙O2 during cycling at 100 W was lowered ( P < 0.05 ) from 55 % ± 7 % to 50 % ± 8 % V˙O2max over 6 months , with no changes in DAG . In STG , resting HR was lowered by 8 ± 11 bpm ( P < 0.05 ) , and the augmentation index ( a measure of arterial stiffness ) was lowered ( P < 0.05 ) by 7.3 ± 14.0 over 6 months , with no change in DAG . CONCLUSIONS Six months of soccer training improved aerobic fitness , reduced blood pressure , and result ed in an array of other favorable effects on cardiovascular risk profile for untrained middle-age hypertensive men . Soccer training , therefore , may be a better nonpharmacological treatment for hypertensive men than traditional physician-guided advice We examined the effect of the number of players on the activity profile and physiological response to small-sided recreational football games with fixed relative pitch size . Twelve untrained men ( age : 33.0 ± 6.4 ( ± st and ard deviation ) years , fat% : 22.4 ± 6.1 % , VO₂ max : 43.3 ± 5.2 mL/min/kg ) completed three football sessions of 4 times 12 min with 3v3 , 5v5 , or 7v7 in a r and omized order . Pitch sizes were 80 m(2 ) per player . Activity profile ( 10 Hz global positioning system ) , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were measured , and blood sample s were collected before and during games . Average HR was 84.1 ± 3.9 , 84.5 ± 5.0 , and 82.8 ± 5.1 % HRmax for 3v3 , 5v5 , and 7v7 , respectively , with no difference between game formats . High blood lactate ( 5.9 ± 2.9 , 5.9 ± 2.4 , and 5.5 ± 2.9 mmol/L ) and plasma NH₃ concentrations ( 124 ± 48 , 112 ± 38 , and 126 ± 55 μmol/L , respectively ) were observed during 3v3 , 5v5 , and 7v7 , respectively , with no difference between formats . Similar total distance ( 3676 ± 478 , 3524 ± 467 , and 3577 ± 500 m ) , high-intensity distance ( 349 ± 145 , 406 ± 134 , and 409 ± 165 m ) , and RPE ( 4.7 ± 1.6 , 4.9 ± 2.1 , and 4.6 ± 1.8 ) were also observed . The number of intense accelerations ( 500 ± 139 vs 459 ± 143 and 396 ± 144 ) were higher ( P < 0.05 ) during 3v3 than 5v5 and 7v7 . In conclusion , the intensity is high during small-sided recreational football games , with similar physiological responses for 6 - 14 players when pitch size is adapted , providing further evidence that effective recreational football training is easy to organize We examined the physical dem and s of small-sided soccer games in untrained middle-age males and muscle adaptations and performance effects over 12 weeks of recreational soccer training in comparison with continuous running . Thirty-eight healthy subjects ( 20–43 years ) were r and omized into a soccer ( SO ) , running ( RU ) and control ( CO ) group . Two – three weekly 1-h training sessions were performed . Muscle lactate ( 30.1 ± 4.1 vs. 15.6 ± 3.3 mmol/kg d.w . ) , blood lactate , blood glucose and time above 90 % HRmax ( 20 ± 4 % vs. 1 ± 1 % ) were higher ( p < 0.05 ) during training in SO than in RU . After 12 weeks of training , quadriceps muscle mass and mean muscle fibre area were 9 and 15 % larger ( p < 0.05 ) in SO , but unaltered in RU , and in SO , the fraction of FTx fibres was lowered ( 10.7 ± 1.8 vs. 17.9 ± 3.2 % ) . In SO , citrate synthase activity was 10 and 14 % higher ( p < 0.05 ) after 4 and 12 weeks , but unaltered in RU . After 4 weeks VO2max and Yo-Yo IE2 performance were elevated ( p < 0.05 ) to a similar extent in SO ( 7 and 37 % ) and RU ( 6 and 36 % ) but increased further ( p < 0.05 ) from 4 to 12 weeks in SO ( 6 and 23 % ) . In SO , 30-m sprint performance was improved ( p < 0.05 ) by 0.11 ± 0.02 s. Blood lactate during running at 11 km/h was lowered ( p < 0.05 ) from 0 to 4 and 4 to 12 weeks ( 2.6 ± 0.3 vs. 3.8 ± 0.6 vs. 6.1 ± 0.9 mM ) and from 0 to 12 weeks in RU . No changes occurred for CO . In conclusion , recreational soccer organized as small-sided games stimulates both aerobic and anaerobic energy turnover and is an effective type of training leading to significant cardiovascular and muscular adaptations as well as performance enhancements throughout a 12-week training period 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 examined the effect of recreational football and resistance training on bone mineral density ( BMD ) and bone turnover markers ( BTMs ) in elderly men . Twenty-six healthy sedentary men ( age 68.2 ± 3.2 years ) were r and omized into three groups : football ( F ; n = 9 ) and resistance training ( R ; n = 9 ) , completing 45 - 60 min training two to three times weekly , and inactive controls ( C ; n = 8) . Before , after 4 months , and after 12 months , BMD in proximal femur ( PF ) and whole body ( WB ) were determined together with plasma osteocalcin ( OC ) , procollagen type-1 amino-terminal propeptide ( P1NP ) , and carboxy-terminal type-1 collagen crosslinks ( CTX-1 ) . In F , BMD in PF increased up to 1.8 % ( P < 0.05 ) from 0 to 4 months and up to 5.4 % ( P < 0.001 ) from 0 to 12 months ; WB-BMD remained unchanged . After 4 and 12 months of football , OC was 45 % and 46 % higher ( P < 0.001 ) , and P1NP was 41 % and 40 % higher ( P < 0.001 ) than at baseline , respectively . After 12 months , CTX-1 showed a main effect of 43 % ( P < 0.05 ) . In R and C , BMD and BTM remained unchanged . In conclusion , 4 months of recreational football for elderly men had an osteogenic effect , which was further developed after 12 months , whereas resistance training had no effect . The anabolic response may be due to increased bone turnover , especially improved bone formation The aim of this study was to examine the effect of intense intermittent exercise performed as soccer training or interval running in comparison with continuous endurance running exercise on postural balance in young healthy untrained males . Young sedentary men were r and omized to soccer training ( SOC , n = 10 ) , continuous running ( RUN ; n = 9 ) , high-intensity interval running ( INT ; n = 7 ) or no training ( CON ; n = 9 ) . Postural balance was evaluated pre and post 12 weeks of training using a 30-s single-leg stance test on a force plate ( AMTI ) to yield center of pressure ( CoP ) sway path and 1-min beam st and ing ( Flamingo test ) . CoP sway length decreased by 18.2 % ( p < 0.01 ) , 14.6 % ( p < 0.05 ) and 12.8 % ( p < 0.05 ) in SOC , INT and RUN , respectively . CoP sway area decreased in SOC ( −30.2 % ; p < 0.01 ) and INT ( −23.4 % ; p < 0.01 ) but remained unaffected in RUN . Acceleration parameters ( Mean CoP acc , SD accX , SD accY ) decreased in SOC only ( 17–19 % , p < 0.05 ) . All training groups demonstrated fewer falls ( 37–41 % , p < 0.01 ) in the Flamingo test . No changes were observed in CON . Relationships ( r > 0.40 ) were observed between pre-training values in CoP sway area versus muscle fiber area , explosive muscle strength and countermovement jump velocity . Postural control was improved in response to 12 weeks of soccer training and high-intensity interval running , respectively , while less-marked changes were observed following continuous running . Notably , the reduced variability in CoP acceleration after soccer training indicates that this training regimen may produce superior improvements in postural sensory-motor function The present intervention was design ed to investigate whether a 14-week period of regular recreational association football ( F ) or endurance running ( R ) has an effect on the risk of falls and bone fractures due to gains in muscle function and volumetric bone mineral density ( vBMD ) . Fifty healthy untrained Danish premenopausal women were r and omized into two training groups ( F and R ) that trained 1.8+/-0.3 ( + /-SD ) and 1.9+/-0.3 h/week , respectively , and these groups were compared with an inactive control group ( C ) . Jumping and dynamic muscle strength were tested and tibial vBMD was measured using peripheral quantitative computed tomography . Total vBMD in left and right tibia increased by 2.6+/-2.3 % and 2.1+/-1.8 % ( P<0.005 ) , respectively , in F and by 0.7+/-1.3 % ( P=0.05 ) and 1.1+/-1.5 % ( P<0.01 ) , respectively , in R without any significant changes in C. Similar results were found for trabecular vBMD . In F , peak jump power increased by 3+/-6 % ( P<0.05 ) , and hamstring strength during fast ( 240 degrees /s ) and slow ( 30 degrees /s ) contractions increased by 11+/-25 % and 9+/-21 % , respectively , ( P<0.05 ) without any significant changes in R or C. In conclusion , 14 weeks of regular recreational football improved peak jump power , maximal hamstring strength and vBMD in the distal tibia , suggesting a decreased fracture risk due to stronger bones and a reduced risk of falling Abstract The effects of a recreational soccer program ( RSP ) upon body composition , heart rate variability ( HRV ) , biochemical markers , cardio-respiratory fitness , and endothelial function in obese adolescents were investigated . A r and omised controlled clinical trial was conducted with 30 adolescents aged 12–17 years and body mass index ( BMI ) > 2 st and ard deviations of WHO reference values , which were assigned to RSP ( n = 10 , 2 girls ) and obese control ( n = 10 , 4 girls ) groups . The 12-week RSP included 60-min sessions performed 3 times/week . BMI , waist circumference , blood pressure , blood glucose , lipid profile , insulin , C-reactive protein , HRV , and maximal oxygen consumption ( VO2peak ) were evaluated following st and ardised procedures . Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography . After intervention , RSP exhibited significant reductions in BMI ( −0.7 ± 0.2 kg · m–2 ) , waist circumference ( −8.2 ± 1.4 cm ) , % body fat ( −2.2 ± 0.4 % ) , systolic blood pressure ( −5.0 ± 2.3 mmHg ) , total cholesterol ( −16.2 ± 5.8 mg · dL−1 ) , triglycerides ( −20.5 ± 12.9 mg · dL−1 ) , C-reactive protein ( −0.06 ± 0.01 mg · dL−1 ) , insulin resistance ( HOMA-IR , −1.4 ± 0.6 ) , and sympathetic activity ( LF , −13.9 ± 6.6 un ) vs. controls ( P < 0.05 ) . Significant increase was observed in parasympathetic activity ( HF , 13.9 ± 6.6 un ) , VO2peak ( 7.9 ± 2.8 ml · kg−1 · min−1 ) , and high-density lipoprotein cholesterol ( 11.0 ± 6.3 mg · dL−1 ) ( P < 0.05 ) . Vascular conductance ( 19.5 ± 8.1 ml · min−1 · 100 ml , P = 0.005 ) increased and vascular resistance ( −5.9 ± 2.4 ml · min−1 · 100 ml , P = 0.041 ) decreased in RSP , but not in controls . A 12-week recreational soccer intervention was effective to improve biochemical , cardiovascular , and fitness health markers in obese adolescents The aims of this study were : 1 ) To determine the effects of a 12-week recreational soccer training programme and continuous endurance running on body composition of young adult men and 2 ) to determine which of these two programmes was more effective concerning body composition . Sixty-four participants completed the r and omized controlled trial and were r and omly assigned to one of three groups : a soccer training group ( SOC ; n=20 ) , a running group ( RUN ; n=21 ) or a control group performing no physical training ( CON ; n=23 ) . Training programmes for SOC and RUN lasted 12-week with 3 training sessions per week . Soccer sessions consisted of 60 min ordinary five-a-side , six-a-side or seven-a-side matches on a 30 - 45 m wide and 45 - 60 m long plastic grass pitch . Running sessions consisted of 60 min of continuous moderate intensity running at the same average heart rate as in SOC ( ~80 % HRmax ) . All participants , regardless of group assignment , were tested for each of the following dependent variables : body weight , body height , body mass index , percent body fat , body fat mass , fat-free mass and total body water . In the SOC and RUN groups there was a significant decrease ( p < 0.05 ) in body composition parameters from pre- to post-training values for all measures with the exception of fat-free mass and total body water . Body mass index , percent body fat and body fat mass did not differ between groups at baseline , but by week 12 were significantly lower ( p < 0.05 ) in the SOC and RUN groups compared to CON . To conclude , recreational soccer training provides at least the same changes in body composition parameters as continuous running in young adult men when the training intensity is well matched Abstract The present study investigated the heart rate ( HR ) response to various types of physical education ( PE ) activities for 8- to 9-year-olds ( five school classes , n = 93 ) and the fitness effects of a short-term PE training programme ( three of the five classes , n = 59 ) with high compared to low-to-moderate aerobic intensity . HR was recorded during small-sided indoor soccer ( SO ) , basketball ( BB ) , unihockey ( UH ) , circuit training ( CT ) , walking ( W ) and Nintendo Wii Boxing ( NWB ) and Nintendo Wii Tennis ( NWT ) . Maximal HR ( HRmax ) and physical fitness was determined by the Yo-Yo Intermittent Recovery Level 1 Children 's test ( YYIR1C ) test . Following cluster r and omisation , three classes were tested before and after 6 wks with 2 × 30 min/wk SO and UH lessons [ high-intensity ( HI ) , 2 classes , n = 39 ] or low-to-moderate intensity PE lessons ( CON , 1 class , n = 20 ) . Average HR in SO ( 76 ± 1 % HRmax ) , BA ( 77 ± 1 % HRmax ) and UH ( 74 ± 1 % HRmax ) was higher ( P < 0.05 ) than in CT ( 62 ± 1 % HRmax ) , W ( 57 ± 1 % HRmax ) , NWB ( 65 ± 2 % HRmax ) and NWT ( 57 ± 1 % HRmax ) . Time with HR > 80 % and 90 % HRmax , respectively , was higher ( P < 0.05 ) in SO ( 42 ± 4 and 12 ± 2 % ) , BB ( 41 ± 5 and 13 ± 3 % ) and UH ( 34 ± 3 and 9 ± 2 % ) than in CT , W and NW ( 0–5 % ) , with time > 80 % HRmax being higher ( P < 0.05 ) in SO than UH . After 6 wk , YYIR1C performance was increased ( P < 0.05 ) by 22 % in HI ( 673 ± 57 to 821 ± 71 m ) , but unaltered in CON ( 674 ± 88 to 568 ± 81 m ) . HR 2 min into YYIR1C was lowered ( P < 0.05 ) in HI after 6 wks ( 92.4 ± 0.8 to 89.1 ± 0.9 % HRmax ) , but not in CON . In conclusion , ball games elicited high aerobic loading for young schoolchildren and a short-term , low-volume ball game PE-intervention improved physical fitness . Traditional PE sessions had no effects on intermittent exercise performance This r and omized controlled study investigated the effectiveness of soccer and Zumba on fitness and health indicators in female participants recruited from a workplace . One hundred seven hospital employees were cluster-r and omized to either a soccer group ( SG ) , Zumba group ( ZG ) , or control group ( CG ) . Intervention effects for the two training groups were compared with CG . The training was conducted outside working hours as 2 - 3 1-h sessions per week for 12 weeks . Peak oxygen uptake ( VO2peak ) , fat percentage , fat mass , bone mineral content , and plasma osteocalcin were measured before and after the intervention period . Based on intention-to-treat-analyses , SG significantly improved the VO2peak relative to body mass ( 5 % ; P = 0.02 ) and decreased heart rate during 100-W cycle exercise ( -7 bpm ; P = 0.01 ) , total body fat percentage ( -1.1 % ; P = 0.002 ) , and total body fat mass ( -1.0 kg ; P = 0.001 ) compared with CG . ZG significantly improved the VO2peak relative to body mass ( 5 % ; P = 0.03 ) and decreased total fat mass ( -0.6 kg ; P < 0.05 ) compared with CG . Plasma osteocalcin increased in SG ( 21 % ; P < 0.001 ) and ZG ( 10 % ; P = 0.01 ) compared with CG . The present study indicates that workplace initiated short-term soccer training as well as Zumba outside working hours may result in fitness and modest health benefits among female hospital employees We evaluated the effects of recreational football training combined with calorie-restricted diet ( football + diet ) vs calorie-restricted diet alone ( diet ) on aerobic fitness , lipid profile , and insulin resistance indicators in type 2 diabetes ( T2D ) patients . Forty-four T2D patients aged 48 - 68 years ( 27 females , 17 males ) were r and omly allocated to the football + diet group ( FDG ; n = 22 ) or to the diet group ( DG ; n = 22 ) , of whom 19 FDG and 15 DG subjects completed the study . The football training was performed for 3 × 40 min/week for 12 weeks . Dual-energy X-ray absorptiometry scanning , treadmill testing , and fasting blood samplings were performed pre and post-intervention . After 12 weeks , maximal oxygen uptake ( VO₂max ) was elevated ( P < 0.05 ) by 10 ± 4 % in FDG but not in DG ( -3 ± 4 % , P < 0.05 ) . After 12 weeks , reductions in blood triglycerides ( 0.4 ± 0.1 mmol/L ) , total cholesterol ( 0.6 ± 0.2 mmol/L ) , low-density lipoprotein , and very low-density lipoprotein levels were observed only in FDG . Fat mass decreased ( P < 0.05 ) by 3.4 ± 0.4 kg in FDG and 3.7 ± 0.4 kg in DG . The lower ( P < 0.05 ) glucagon and homeostatic model assessment of insulin resistance indicated an improvement in insulin sensitivity in FDG . In conclusion , football combined with restricted diet was effective in enhancing VO₂max , reducing total cholesterol and triglycerides , and increasing insulin sensitivity , potentially providing better tools for the prevention of T2D complications than diet alone The present study examined the effects of short-term recreational football training on blood pressure ( BP ) , fat mass , and fitness in sedentary , 35 - 50-year-old premenopausal women with mild hypertension . Forty-one untrained , hypertensive women were r and omized into a football training group ( n = 21 ; FTG ) and a control group ( n = 20 ; CON ) . FTG performed 45 ± 1 1-h small-sided football training sessions during the 15-week intervention period . BP , body composition ( dual-energy x-ray absorptiometry ) , blood lipid profile , and fitness level were determined pre- and post-intervention . After 15 weeks , systolic and diastolic BP , respectively , were lowered more ( P < 0.05 ) in FTG ( -12 ± 3 and -6 ± 2 mmHg ) than in CON ( -1 ± 1 and 1 ± 2 mmHg ) . Total body fat mass decreased more ( P < 0.05 ) in FTG than in CON during the 15-week intervention period ( -2.3 ± 0.5 kg vs 0.4 ± 0.3 kg ) . After 15 weeks , both total cholesterol ( -0.4 ± 0.1 mmol/L vs 0.1 ± 0.2 mmol/L ) and triglyceride ( -0.2 ± 0.1 mmol/L vs 0.3 ± 0.2 mmol/L ) were lowered more ( P < 0.05 ) in FTG than in CON . Yo-Yo intermittent endurance level 1 test performance increased more ( P < 0.05 ) in FTG than in CON ( 111 ± 18 % vs 1 ± 3 % ) during the 15-week intervention period . In conclusion , short-term football training result ed in a marked reduction in BP and induced multiple improvements in fitness and cardiovascular health profile of untrained , premenopausal women with mild hypertension |
11,275 | 16,855,992 | There was clearer evidence of benefit in the subgroup of trials recruiting smokers motivated to quit .
Proactive telephone counselling helps smokers interested in quitting .
Three or more calls increases the odds of quitting compared to a minimal intervention such as providing st and ard self-help material s , brief advice , or compared to pharmacotherapy alone .
Telephone quitlines provide an important route of access to support for smokers , and call-back counselling enhances their usefulness | BACKGROUND Telephone services can provide information and support for smokers .
Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines .
OBJECTIVES To evaluate the effect of proactive and reactive telephone support to help smokers quit . | This article evaluates the effects and use of adjuncts to a televised smoking cessation program , based on the American Lung Association 's " Freedom From Smoking in 20 Days . " Subjects were r and omized to maintenance and control conditions . The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline . The maintenance condition did not increase cessation at any wave of interviewing , assessed by multiple point or point prevalence of abstinence . Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage . Rates of use of the telephone hotline were low . The newsletters appear to be useful to smokers who are predisposed to use written material Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care BACKGROUND Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population . The intervention provides individualized feedback that guides participants through the stages of change for cessation . Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer design ed to produce nicotine fading could produce preventive programs with greater population impacts . METHODS Four interventions were compared : ( a ) the interactive expert system intervention ; ( b ) the expert system intervention plus counselor calls ; ( c ) the expert system intervention plus the stimulus control computer ; and ( d ) an assessment only condition . A 4 ( intervention ) x 4 ( occasions ) ( 0,6,12 , and 18 months ) design was used . Smokers were contacted at home via telephone or mail . The initial subject pool was the 24,178 members of a managed care company . Screening was completed for 19,236 members ( 79.6 % ) , of whom 4,653 were smokers ; 85.3 % of the smokers were enrolled . RESULTS Thirty-eight percent were in the precontemplation stage , 45 % in the contemplation stage , and only 17 % in the preparation stage . At 18 months , the expert system result ed in 23.2 % point prevalence abstinence , which was 33 % greater than that of assessment only . The counselor enhancement produced increased cessation at 12 months but not at 18 months . The stimulus control computer produced no improvement , result ing in 20 % worse cessation rates than the assessment only condition . CONCLUSIONS The enhanced conditions failed to outperform the expert system alone . The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes ( both AIDS- and non-AIDS-related ) compared with HIV-positive nonsmokers . Therefore , efforts to design and implement effective cessation programs for this ever-growing special population are warranted . The present study assessed the effects of a cell phone intervention ( CPI ) on hypothesized mediators ( i.e. , changes in depression , anxiety , social support , and self-efficacy ) demonstrated to influence cessation outcomes in other population s. Ninety-five participants from an inner-city AIDS clinic were r and omized to receive either the CPI or recommended st and ard of care ( RSOC ) smoking cessation treatment . Participants r and omized to the RSOC group ( n=47 ) received brief advice to quit , a 10-week supply of nicotine patches , and self-help material s. Participants r and omized to the CPI group ( n=48 ) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones . A series of regression analyses ( linear and logistic ) was used to assess the relationships between treatment group , the hypothesized mediators , and biochemically confirmed smoking cessation outcomes . Results indicated that the CPI group experienced greater reductions in anxiety and depression , and increases in self-efficacy compared with the RSOC group . Further , changes in depression , anxiety , and self-efficacy weakened the association between treatment group and cessation outcome . The mediator hypothesis , however , for social support was rejected , as the difference score was not significantly associated with treatment group . These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy BACKGROUND This study was conducted to determine the efficacy of the nicotine patch in smoking cessation when combined with self-help material s , three brief visits , and telephone counseling . METHODS One hundred fifty-nine healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking were enrolled in a double-blind trial with 6-week treatment and 6-month follow-up periods . After review of self-help material s , subjects were r and omly assigned to regimens of nicotine or placebo patches . Subjects wore two patches per day for 4 weeks ( 25 mg of nicotine per 24 hours ) , then one patch per day for 2 weeks . Return visits were at the ends of weeks 4 and 6 . Telephone counseling was given during weeks 1 , 2 , 3 , and 5 . Abstinence at 6 weeks was defined as zero cigarettes smoked for the previous 28 days , verified by exhaled carbon monoxide less than 8 ppm at 4 weeks and 6 weeks . Abstinence at 3 and 6 months was defined as self-report of zero cigarettes since the previous contact , verified by carbon monoxide value at 6 months . RESULTS Abstinence rates at 6 weeks , 3 months , and 6 months were 29.5 % , 21.8 % , and 20.5 % in the active group , and 8.8 % , 3.8 % , and 2.5 % in the placebo group ( P < or = .001 for each comparison ) , respectively . Skin irritation was the main side effect , causing 1.3 % to drop out . CONCLUSION The nicotine patch is efficacious in smoking cessation over a 6-month period , when combined with only self-help material s , three brief visits , and telephone counseling This study was based on a ten-year follow-up of smokers who had participated in a r and omized controlled trial of a behavioral self-help program for smoking cessation . The original sample was made up of 200 smokers assigned at r and om to two treatment groups . Ten years later 93.5 % ( n=187 ) of the sample were successfully located ( of the 13 not located , 6 had died ) , from whom information was obtained about their current state and the evolution of their smoking over the 10-year period . Reported abstinence at this follow-up was confirmed by carbon monoxide in expired air . Significant differences were found in the abstinence rates of the two groups at the follow-ups 1 year ( 14 % vs. 28 % ) and 2 years ( 13 % vs. 24 % ) after the end of the treatment . After 10 years 26 % ( n=52 ) of the total sample were abstinent . Over the ten-year period , 62.0 % tried to give up smoking at some point , the mean figure for attempts being 1.3 . According to the results of the 10-year follow-up , low nicotine dependence at pretreatment is a major factor predicting long-term cessation in smokers Background Smoking is more prevalent among lower-income individuals and certain racial/ethnic minorities . Addressing tobacco cessation among diverse population s is an urgent public health priority . As Internet use continues to rise among all segments of the US population , Web-based interventions have enormous potential to reach priority population s. Conducting Web-based smoking cessation research in priority population s requires psychometrically sound measurement instruments . To date , only one published study has examined the psychometric properties of Internet-administered measures commonly used in Web-based cessation trials . However , the sample was homogeneous with regard to race/ethnicity and income . We sought to replicate and extend these findings in a more diverse sample of smokers . Objective The aim was to examine the internal consistency and test-retest reliability of measures commonly used in smoking cessation clinical trials among racial/ethnic minorities and smokers with lower income . Methods Participants were enrolled in a r and omized trial of the efficacy of an Internet smoking cessation program between June 2005 and September 2006 . Following a baseline telephone assessment and r and omization into the parent trial , participants were recruited to the reliability sub study . In phase I of recruitment , all participants in the parent trial were recruited to the sub study ; in phase II , all consecutive racial/ethnic minority participants in the parent trial were recruited . Race and ethnicity were assessed via self-report using two st and ard items from the US Office of Management and Budget . An email was sent 2 days after the telephone assessment with a link to the Internet survey . Measures examined were quit methods , perceived stress , depression , social support , smoking temptations , alcohol use , perceived health status , and income . Internal consistency and test-retest reliability of Internet- versus telephone-administered measures were examined within four strata defined by race/ethnicity ( non-Hispanic White , racial/ethnic minority ) and annual household income ( US $ 40,000 or less , more than $ 40,000 ) . Results Of the 442 individuals invited , 319 participated ( 72 % response rate ) : 52.4 % were non-Hispanic White , 22.9 % Black , 11.6 % Hispanic , 7.8 % Asian , 4.4 % American Indian / Alaska Native , and 1 % Native Hawaiian / Other Pacific Isl and er . About half ( 49.4 % ) reported an annual household income of US $ 40,000 or less , and 25.7 % had a high school degree or less . Test-retest reliability was satisfactory to excellent across all strata for the majority of measures examined : 9 of 12 continuous variables had intraclass correlation coefficients ≥ 0.70 , and 10 of 18 binary variables and both ordinal variables had kappa coefficients ≥ 0.70 . Test-retest reliability of several quit methods varied across strata . Conclusions Race/ethnicity and income do not affect the psychometric properties of most Internet-administered measures examined . This knowledge adds to the confidence of conducting Web-based smoking cessation research and strengthens the scientific rigor of collecting information via the Internet on racial/ethnic minority and low-income subgroups . Trial registration clinical trials.gov NCT00282009 ( parent trial 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 OBJECTIVE To provide an overview of the California Smokers ' Helpline , an increasingly popular telephone program for tobacco cessation in California since 1992 . As many states , regions , and nations are contemplating various telephone programs as part of large scale anti-tobacco campaigns , this paper presents a practical model . DESIGN The Helpline provides Californians with free cessation services that include counselling , self help quit kits , and cessation related information . Services are provided in six spoken language s plus a line for the hearing impaired . The program is promoted statewide by media campaigns , health care providers , local tobacco control programs , and the public school system . SETTING The Helpline is central ly operated through the University of California , San Diego and provides services statewide via telephone . RESULTS The Helpline has served over 100 000 tobacco users and has become the chief cessation re source for the Comprehensive Tobacco Control Program in California . Media was the most important referral source for Helpline callers ( 50 % ) , followed by health care providers ( 20 % ) . About one third of the callers were ethnic minorities and 17 % were 24 years old or younger . Compared to California smokers in general , the callers were more dependent on nicotine and more likely to live with other smokers , but they were also more likely to have tried to quit recently and were more ready to try again . Two r and omised trials have demonstrated the efficacy of the Helpline 's counselling protocol . CONCLUSION A central ised helpline operation can be an accessible and effective service for tobacco users and should be included in any large scale , comprehensive tobacco control program Abstract Objective : To evaluate the effectiveness of an antismoking campaign conducted by the Health Education Board for Scotl and . Design : Descriptive survey of adult callers to a telephone helpline ( Smokeline ) for stopping smoking ; panel study of a r and om sample of adult callers ; assessment of changes in prevalence of smoking in Scotl and before and after introduction of the helpline Setting : Telephone helpline . Subjects : Callers to Smokeline over the initial one year period . Detailed information was collected on a 10 % sample ( n=8547 ) . A cohort of adult smokers who called Smokeline ( total n=848 ) was followed up by telephone interview three weeks , six months , and one year after the initial call . Main outcome measures : Numbers of adult smokers calling helpline ; changes in smoking behaviour , especially stopping smoking among cohort members ; and changes in prevalence of smoking in the general population . Results : An estimated 82 782 regular adult smokers made genuine contact with Smokeline over the year , representing about 5.9 % of all adult smokers in Scotl and . At one year 143 of the cohort of 848 callers ( 23.6 % ; 95 % confidence interval 20.2 % to 27.0 % ) reported that they had stopped smoking , and 534 ( 88.0 % ; 85.4 % to 90.6 % ) reported having made some change . About 19 500 ( 16 700 to 22 350 ) adult smokers , equivalent to 1.4 % ( 1.2 % to 1.6 % ) of the mean adult smoking population , stopped smoking with direct help from Smokeline . During the second year of the campaign ( 1994 ) smoking prevalence among 25 - 65 year olds in Scotl and was 6 % ( 2.0 % to 10.0 % ) lower than it had been before the start of the campaign . Conclusion : The Health Education Board for Scotl and 's antismoking campaign reached a high number of adult smokers , was associated with a highly acceptable quit rate among adults given direct help through Smokeline , and contributed considerably to an accelerated decline in smoking prevalence in Scotl and . Key messages There was an unprecedented response to the antismoking campaign of the Health Education Board for Scotl and , with an estimated 5.9 % of adult smokers in Scotl and responding to the invitation to call Smokeline , a free telephone helpline , in its first year of operation A panel study of callers to Smokeline , with telephone interviewing , obtained an acceptable response rate of 71.6 % at one year follow up Nearly a quarter ( 23.6 % ) of smokers who called the helpline were not smoking at the one year follow up , a success rate that exceeds a proposed st and ard for comparable health education and promotion interventions The Smokeline campaign contributed considerably to an accelerated ( 6 % ) reduction in smoking among people aged 25 - 65 in Scotl and during 1992 - 4 The study findings provide further evidence of the efficacy of mass media antismoking initiatives with a social support During June 2000-May 2001 , the American Cancer Society conducted a r and omized trial of telephone counseling among more than 3,500 current smokers who called to seek assistance in quitting . All eligible callers were r and omized to receive either self-help booklets through the mail or booklets and up to 5 sessions of telephone counseling . Approximately 12 % ( 420/3,522 ) of study participants were 18 - 25 years of age . Using intent to treat analyses , 3- and 6-month quit rates among both younger and older smokers were significantly higher among those who received telephone counseling than among those who received self-help booklets only . Three-month rates were 20 % versus 9 % for 18 - 25 year olds and 15 % versus 10 % for older adults . Results indicate that younger smokers can benefit from telephone counseling BACKGROUND This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking . METHODS A total of 214 Medicaid-eligible women smokers of childbearing age were r and omized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months . Assessment s were conducted by telephone at baseline , 10 days , and 3 and 6 months after enrollment . RESULTS At the 3-month follow-up , significantly more women in the patch plus proactive telephone support condition were abstinent ( 42 % ) compared to the patch only condition ( 28 % ) ( P = 0.03 ) . Similarly , more women in the experimental condition were abstinent at both the 10-day and 3-month assessment s ( 32 v 19 % , P = 0.02 ) . However , differences were not found at the 6-month follow-up , suggesting that the addition of proactive telephone peer support enhanced short-term , but not long-term cessation . CONCLUSIONS This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population BACKGROUND Smokers receiving pharmacotherapy and individualized smoking cessation counseling through telephone quitlines have been found to have higher quit rates than smokers receiving pharmacotherapy alone . Health plans are often positioned to encourage their members to use quitline services in addition to pharmacotherapy . OBJECTIVE To determine if healthcare members who were receiving pharmacotherapy increased their participation in smoking quitline services after receiving proactive telephone calls or postcards . STUDY DESIGN R and omized controlled trial . METHODS Health plan members filing pharmacotherapy cl aims were identified weekly from health plan pharmacy cl aims data and r and omized to 1 of the following 3 conditions : control , recruitment postcard , or recruitment telephone call by a nurse quitline counselor . Enrollment of study members into the quitline program was tracked for 1 month after r and omization . RESULTS During 5 months , 625 individuals were identified for participation in the study , with the following enrollment into the program : 0 % to the control group , 1.3 % to the postcard group , and 20.6 % to the telephone call group ( P < .001 for significance by group ) . Although costs for the telephone intervention were the most expensive , it was also the most cost effective , given its success in enrolling members into the program . CONCLUSIONS Proactive telephone calling by smoking cessation nurse counselors to smokers receiving pharmacotherapy may be an effective method of enrolling smokers into a cessation quitline . Health plans should consider proactive telephone recruitment to improve use of quitline services Purpose . To determine the effectiveness of a multicomponent smoking cessation program supplemented by incentives and team competition . Design . A quasi-experimental design was employed to compare the effectiveness of three different smoking cessation programs , each assigned to separate worksites . Setting . The study was conducted from 1990 to 1991 at three aerospace industry worksites in California . Subjects . All employees who were current , regular tobacco users were eligible to participate in the program offered at their site . Intervention . The multicomponent program included a self-help package , telephone counseling , and other elements . The incentive-competition program included the multicomponent program plus cash incentives and team competition for the first 5 months of the program . The traditional program offered a st and ard smoking cessation program . Measures . Self-reported question naires and carbon monoxide tests of tobacco use or abstinence were used over a 12-month period . Results . The incentive-competition program had an abstinence rate of 41 % at 6 months ( n = 68 ) , which was significantly better than the multicomponent program ( 23 % , n = 81 ) or the traditional program ( 8 % , n = 36 ) . At 12 months , the quit rates for the incentive and multicomponent programs were statistically indistinguishable ( 37 % vs. 30 % ) , but remained higher than the traditional program ( 11 % ) . Chi-square tests , t-tests , and logistic regression were used to compare smoking abstinence across the three programs . Conclusions . Offering a multicomponent program with telephone counseling may be just as effective for long-term smoking cessation as such a program plus incentives and competition , and more effective than a traditional program Purpose The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training ( DSMT ) . Methods A r and omized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center . A total of 114 subjects were r and omized to intervention ( n = 57 ; face-to-face motivational interviewing plus telephone counseling and offering of medication ) or st and ard care ( n = 57 ) . Outcome measures included tobacco cessation rates , mean number of cigarettes smoked , A1C , weight , blood pressure , and lipids . Results Intensive intervention using motivational interviewing integrated into a st and ard DSMT program result ed in a trend toward greater abstinence at 3 months of follow-up in those receiving the intervention . However , this same trend was not observed at 6 months . The addition of this structured smoking cessation intervention did not negatively affect either diabetes education or other measures of diabetes management , including A1C values OBJECTIVE This study evaluated the reach , initial effectiveness , and potential moderators and mediators of results of a smoking reduction program . DESIGN A generally representative sample of 320 adult smokers from an HMO , scheduled for outpatient surgery or a diagnostic procedure , were r and omized to enhanced usual care or a theory-based smoking reduction intervention that combined telephone counseling and tailored newsletters . MAIN OUTCOME MEASURES Self-reported number of cigarettes smoked and carbon monoxide levels . RESULTS The intervention enrolled 30 % of known eligible smokers and produced reductions of 3 cigarettes per day greater than enhanced usual care . Intervention participants were significantly more likely than control participants to achieve at least a 50 % reduction in self-reported number of cigarettes using complete cases , imputation analyses , and intent-to-treat procedures . Similar patterns were seen for carbon monoxide results but were significant only in complete case analyses . The intervention was generally robust across patient characteristics ( e.g. , education , ethnicity , health literacy , and dependence ) and phone counselors . CONCLUSION Initial results suggest that this program has potential to reach and assist smokers who may not participate in cessation programs . Additional research is indicated to enhance intervention effects , assess maintenance , and evaluate public health impact The purpose of this prospect i ve , r and omized controlled study was to determine the efficacy of an intensified , late pregnancy , smoking cessation intervention for resistant pregnant smokers ( n = 269 ) . Participants received 3 - 5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter ; at 28 weeks , all had been smoking in the past 28 days . The experimental group received a stage of change-based , personalized feedback letter and two telephone counseling calls using Motivational Interviewing ( MI ) strategies . The control group received care as usual . The 34th week cotinine data demonstrated no overall difference between groups . However , an implementation analysis suggested that 43 % of women who received the full intervention ( E2 ) were classified as not smoking compared to 34 % of the control group . At 6 weeks postpartum , 27.1 % of the E2 group reported being abstinent or light smokers vs. 14.6 % of the controls . No differences were detected at 3 and 6 months postpartum . Results lend preliminary but very modest support for this intervention with resistant pregnant smokers . Improvements in the intervention and implementation issues are discussed Background Referral of patients to smoking cessation telephone counseling ( i.e. , quitline ) is an underutilized re source by primary care physicians . Previously , we conducted a r and omized trial to determine the effectiveness of benchmarked feedback on clinician referrals to a quitline . Subsequently , we sought to underst and the successful practice s used by the high-referring clinicians , and the perceptions of the barriers of referring patients to a quitline among both high and non-referring clinicians in the trial . Methods We conducted a qualitative sub- study with subjects from the r and omized trial , comparing high- and non-referring clinicians . Structured interviews were conducted and two investigators employed a thematic analysis of the transcribed data . Themes and included categories were organized into a thematic framework to represent the main response sets . Results As compared to non-referring clinicians , high-referring clinicians more often reported use of the quitline as a primary source of referral , an appreciation of the quitline as an additional re source , reduced barriers to use of the quitline referral process , and a greater personal motivation related to tobacco cessation . Time and competing dem and s were critical barriers to initiating smoking cessation treatment with patients for all clinicians . Clinicians reported that having one referral source , a referral coordinator , and reimbursement for tobacco counseling ( as a billable code ) would aid referral . Conclusion Further research is needed to test the effectiveness of new approaches in improving the connection of patients with smoking cessation re sources .Trial Registration Number Clinical trials.gov Many patients attempt to stop smoking during hospitalization , but most relapse after discharge . This study developed and evaluated a brief smoking-cessation and relapse-prevention program for hospitalized smokers . All hospitalized smokers ( n=1,119 ) were identified by question naire at hospital admission and then received either usual care or usual care plus a hospital-based smoking- cessation intervention regardless of interest in stopping smoking . Intervention components included a 20-minute bedside counseling session , a 12-minute videotape , a variety of self-help material s , and a follow-up telephone call . Special attention was given to techniques for preventing relapse after hospital discharge . Defining ex-smokers as those who reported no tobacco use at both 3- and 12-month follow-up assessment s , and counting those lost to follow-up as smokers , the intervention increased the proportion of patients who quit smoking by one half ( 9.2%vs 13.5 % , P<0.05 ) . These results demonstrate the efficacy of a brief in-hospital intervention and suggest that relapse-prevention efforts are needed to convert temporary cessation during hospitalization into longterm abstinence This study reports on the evaluation of the feasibility , cost , and cost-effectiveness of a proactively provided telephone-based motivational smoking cessation intervention to an underserved population of pregnant smokers who may or may not receive ongoing prenatal care . As part of the New Engl and SCRIPT r and omized clinical trial comparing the efficacy of three types of smoking cessation interventions for pregnant smokers , one-third of the women ( n = 358 ) received a motivational telephone counseling intervention ( MI ) delivered by trained counselors using a semistructured protocol . Although this population was very mobile , the MI counselors were able to reach 86 % of the women with at least one call and 46 % received all three calls . The group receiving three MI calls had a cotinine-confirmed quit rate of 23 % . Cost-effectiveness analyses for those women receiving telephone counseling supported the net benefit in favor of the three phone calls compared with the women who did not receive any telephone calls , with an effectiveness to cost ratio of 1:US dollars 84 . Our results suggest that telephone-based motivational smoking cessation counseling may be a feasible and cost-effective method for low-income pregnant smokers enrolled in prenatal care AIM To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline , and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation . DESIGN R and omized controlled trial comparing : ( 1 ) untailored self-help material s ; ( 2 ) computer-generated tailored advice only , and ( 3 ) computer-generated tailored advice plus callback telephone counselling . Assessment surveys were conducted at baseline , 3 , 6 and 12 months . SETTING Victoria , Australia . PARTICIPANTS A total of 1578 smokers who called the Quitline service and agreed to participate . MEASUREMENTS Smoking status at follow-up ; duration of cessation , if quit ; use of nicotine replacement therapy ; and extent of participation in the callback service . FINDINGS At the 3-month follow-up , significantly more ( chi2(2 ) = 16.9 ; P < 0.001 ) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking ( 21 % ) than in either the computer-generated advice only ( 12 % ) or the control condition ( 12 % ) . Proportions reporting not smoking at the 12-month follow-up were 26 % , 23 % and 22 % , respectively ( NS ) for point prevalence , and for 9 months sustained abstinence ; 8.2 , 6.0 , and 5.0 ( NS ) . In the telephone counselling group , those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months ( 10.2 compared with 4.0 , P < 0.05 ) . Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT , but not of computer-generated tailored advice . CONCLUSION Computer-generated tailored advice did not enhance telephone counselling , nor have any independent effect on cessation . This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice Although the prevalence of smoking is lower among Hispanics than among the general population , smoking still levies a heavy public health burden on this underserved group . The current study , Adiós al Fumar ( Goodbye to Smoking ) , was design ed to increase the reach of the Spanish‐ language smoking cessation counseling service provided by the National Cancer Institute 's Cancer Information Service ( CIS ) and to evaluate the efficacy of a culturally sensitive , proactive , behavioral treatment program among Spanish‐speaking smokers . Adiós was a 2‐group r and omized clinical trial evaluating a telephone‐based smoking cessation intervention . Spanish‐speaking smokers ( N = 297 ) were r and omized to receive either st and ard counseling or enhanced counseling ( EC ) . Paid media was used to increase the reach of the Spanish‐ language smoking cessation services offered by the CIS . The Adiós sample was of very low socioeconomic status ( SES ) , and more than 90 % were immigrants . Calls to the CIS requesting smoking cessation help in Spanish increased from 0.39 calls to 17.8 calls per month . The unadjusted effect of EC only approached significance ( OR = 2.4 , P = .077 ) , but became significant after controlling for demographic and tobacco‐related variables ( OR = 3.8 , P = .048 ) . Adiós al Fumar demonstrated that it is possible to reach , retain , and deliver an adequate dose of treatment to a very low SES population that has traditionally been viewed as difficult to reach and hard to follow . Moreover , the findings suggest that a proactive , telephone‐counseling program , based on the Treating Tobacco Use and Dependence Clinical Practice Guideline and adapted to be culturally appropriate for Hispanics , is effective . Cancer 2007 . © 2006 American Cancer Society OBJECTIVE To compare two self-help smoking cessation booklets distributed to callers to a Quitline telephone service in Queensl and ( Australia ) . DESIGN Callers were r and omised to receive either a structured 14-day quit programme ( Time to quit ) or another booklet that described four broad stages of quitting ( Can quit ) . Approximately one month later , these callers were interviewed by telephone . MAIN OUTCOME MEASURES Self-reported smoking status at one month and recent quit attempts together with process measures . RESULTS Altogether , 521 callers ( 78.3 % ) were interviewed . They were heavier smokers when compared with all Queensl and smokers : on average they had smoked for more than 15 years , smoked nearly 25 cigarettes per day , and almost two-thirds had attempted to quit smoking in the past year . In each group , significant proportions either did not begin to use the booklet ( 50.5–56.0 % ) , or did not complete its use ( 77.4–82.3 % ) . There were no differences in the self-reported quit rates at one month ( 17.0%vs 16.1 % ; p = 0.93 ) . In an ordinal regression modelling procedure involving age , sex , number of recent quit attempts , number of cigarettes smoked per day , smoking status of partner , number of five closest friends who smoke , education , and booklet received , only the number of cigarettes smoked per day was significantly related to smoking status at one month . CONCLUSIONS Callers to telephone Quitline services are typically heavier smokers than the general smoking population , and simple strategies , such as self-help booklets , appear to achieve relatively high success . Nevertheless , there is potential to improve the effectiveness of these material s by making a range of material s available and encouraging callers to make a serious attempt to quit smoking Smokers requesting self-help material s for smoking cessation ( N = 2,021 ) were r and omized to receive ( a ) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies , ( b ) the same self-quitting guide with a support guide for the quitter 's family and friends , ( c ) self-quitting and support guides along with four brief counselor calls , or ( d ) a control guide providing motivational and quit tips and referral to locally available guides and programs . Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments . Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide , with fewer behavioral prequitting strategies and more outside treatments . Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates . Telephone counseling increased adherence to the quitting protocol and quit rates BACKGROUND Telephone services that offer smoking-cessation counseling ( quitlines ) have proliferated in recent years , encouraged by positive results of clinical trials . The question remains , however , whether those results can be translated into real-world effectiveness . METHODS We embedded a r and omized , controlled trial into the ongoing service of the California Smokers ' Helpline . Callers were r and omly assigned to a treatment group ( 1973 callers ) or a control group ( 1309 callers ) . All participants received self-help material s. Those in the treatment group were assigned to receive up to seven counseling sessions ; those in the control group could also receive counseling if they called back for it after r and omization . RESULTS Counseling was provided to 72.1 percent of those in the treatment group and 31.6 percent of those in the control group ( mean , 3.0 sessions ) . The rates of abstinence for 1 , 3 , 6 , and 12 months , according to an intention-to-treat analysis , were 23.7 percent , 17.9 percent , 12.8 percent , and 9.1 percent , respectively , for those in the treatment group and 16.5 percent , 12.1 percent , 8.6 percent , and 6.9 percent , respectively , for those in the control group ( P<0.001 ) . Analyses factoring out both the subgroup of control subjects who received counseling and the corresponding treatment subgroup indicate that counseling approximately doubled abstinence rates : rates of abstinence for 1 , 3 , 6 , and 12 months were 20.7 percent , 15.9 percent , 11.7 percent , and 7.5 percent , respectively , in the remaining subjects in the treatment group and 9.6 percent , 6.7 percent , 5.2 percent , and 4.1 percent , respectively , in the remaining subjects in the control group ( P<0.001 ) . Therefore , the absolute difference in the rate of abstinence for 12 months between the remaining subjects in the treatment and control groups was 3.4 percent . The 12-month abstinence rates for those who made at least one attempt to quit were 23.3 percent in the treatment group and 18.4 percent in the control group ( P<0.001 ) . CONCLUSIONS A telephone counseling protocol for smoking cessation , previously proven efficacious , was effective when translated to a real-world setting . Its success supports Public Health Service guidelines calling for greater availability of quitlines BACKGROUND A multicomponent motivational smoking cessation intervention was evaluated in 33 prenatal , family planning , and pediatric services in 12 public health clinics . Clinic-based intervention components were implemented by clinic personnel as part of routine medical visits . METHODS The evaluation design included pre- and postintervention measurements of multiple study outcomes in a baseline ( all clinics prior to the start of the intervention ) and an experimental period ( matchedpair r and om assignment of clinics to intervention or control conditions ) . Subjects were 683 ( baseline ) and 1,064 ( experimental ) smokers with measurements of smoking outcomes at both times . Mixed-effects regressions analyzed individual outcomes clustered within clinics and services . RESULTS Control and intervention clinics had similar outcomes in the baseline period . In the experiment , outcomes improved in the intervention but not in the control clinics . Compared to controls , smokers exposed to the intervention were more likely to have quit ( 14.5 versus 7.7 % ) or take actions toward quitting and had higher mean action , stage of readiness , and motivation to quit scores . These positive effects persisted when clustering within clinics and services was controlled . CONCLUSIONS This intervention , implemented by clinic personnel as part of routine medical visits , was effective under these natural conditions across different types of clinic service Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates PURPOSE Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation . Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a st and ard cessation intervention . EXPERIMENTAL DESIGN Our design was a two-arm trial with eligible smokers r and omized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback ( BF ) . Surveys were conducted at baseline , 6 , and 12 months later . The setting was an inner city community health clinic . African-American patients who were current smokers ( n = 557 ) were identified by chart abstract ion and provider referral . All smokers received a self-help manual and , if appropriate , nicotine patches . Smokers in the BF arm also were offered a blood test for genotyping the GST(3 ) gene ( GSTM1 ) , sent a test result booklet , and called up to four times by a health educator . Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence , i.e. , not smoking at either follow-up or in-between . RESULTS Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm ( 19 % versus 10 % , respectively ; P < 0.006 ) at 6 months but not at 12 months . CONCLUSIONS Smokers agreed to genetic feedback as part of a multicomponent cessation program . Although the program increased short-term cessation rates compared with st and ard intervention , genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions BACKGROUND After an increase in cigarette taxes and implementation of smoke-free workplace legislation , the New York City Department of Health and Mental Hygiene , the New York State Department of Health , and the Roswell Park Cancer Institute undertook large-scale distribution of free nicotine replacement therapy ( NRT ) . We did a 6 month follow-up survey to assess the success of this programme in improving smoking cessation on a population basis . METHODS 34,090 eligible smokers who phoned a toll-free quitline were sent a 6-week course of nicotine patches ( 2 weeks each of 21 mg , 14 mg , and 7 mg per day ) . Brief follow-up counselling calls were attempted . At 6 months after treatment , we assessed smoking status of 1305 r and omly sample d NRT recipients and a non-r and omly selected comparison group of eligible smokers who , because of mailing errors , did not receive the treatment . NRT recipients were compared with local survey-derived data for heavy smokers in New York City . FINDINGS An estimated 5 % of all adults in New York City who smoked ten cigarettes or more daily received NRT ; most ( 64 % ) recipients were non-white , foreign-born , or resided in a low-income neighbourhood . Of individuals contacted at 6 months , more NRT recipients than comparison group members successfully quit smoking ( 33%vs 6 % , p<0.0001 ) , and this difference remained significant after adjustment for demographic factors and amount smoked ( odds ratio 8.8 , 95 % CI 4.4 - 17.8 ) . Highest quit rates were associated with those who were foreign born ( 87 [ 39 % ] ) , older than 65 years ( 40 [ 47 % ] ) , and smoked less than 20 cigarettes per day ( 116 [ 35 % ] ) . Those who received a counselling call were more likely to stop smoking than those who did not ( 246 [ 38 % ] vs 189 [ 27 % ] , p=0.001 ) . With the conservative assumption that every 6-month follow-up survey non-respondent continued to smoke , the stop rate among NRT recipients was 20 % . At least 6038 successful quits were attributable to NRT receipt , and cost was 464 US dollars per quit . INTERPRETATION Easy access to cessation medication for diverse population s could help many more smokers to stop PURPOSE Cancer survivors smoke at rates that are only slightly lower than the general population . This article reports on the final outcomes of Partnership for Health , a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study ( CCSS ) . METHODS This study is a r and omized control trial with follow-up at 8 and 12 months that involved smokers ( n = 796 ) enrolled onto the CCSS cohort . Participants were r and omly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor , tailored and targeted material s , and free nicotine replacement therapy . The intervention was delivered by telephone and postal service mail . RESULTS The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month ( 16.8 % v 8.5 % ; P < .01 ) and 12-month follow-ups ( 15 % v 9 % ; P < or = .01 ) . Controlling for baseline self-efficacy and readiness to change , the intervention group was twice as likely to quit smoking , compared with the self-help group . Smoking cessation rate increased with an increase in the number of counseling calls . The cost of delivering the intervention was approximately 300 dollars per participant . The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit . CONCLUSION Interventions to prevent future illnesses are of critical importance to childhood cancer survivors . The Partnership for Health intervention result ed in a doubling of smoking cessation quit rates . Because of the seriousness of smoking among childhood cancer survivors , this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke OBJECTIVE To evaluate the effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self-help material s. DESIGN R and omized controlled trial . SETTING The UK Quitline . PARTICIPANTS A total of 1508 current smokers and recent ex-smokers . INTERVENTIONS The control group received usual care ( telephone counselling and an information pack sent through the post ) . The intervention group received in addition a computer-generated individually tailored advice letter . MAIN OUTCOME MEASURES All outcomes were assessed at 6-month follow-up . The primary outcome measure was self-reported prolonged abstinence for at least 3 months . Secondary outcomes were self-reported prolonged abstinence for at least 1 month and 7-day and 24-hour point-prevalence abstinence . RESULTS For the sample as a whole , quit rates did not differ significantly between the two conditions . However , among the majority ( n = 1164 ) who were smokers at baseline , quit rates were consistently higher in the intervention group : prolonged abstinence for 3 months , 12.2 % versus 9.0 % [ odds ratio ( OR ) = 1.40 , 95 % confidence interval ( CI ) = 0.96 - 2.04 , P = 0.080 ) ; prolonged abstinence for 1 month , 16.4 % versus 11.3 % ( OR = 1.53 , 95 % CI = 1.09 - 2.15 , P = 0.013 ) ; 7-day point-prevalence abstinence , 18.9 % versus 12.7 % ( OR = 1.59 , 95 % CI = 1.15 - 2.19 , P = 0.004 ) ; 24-hour point-prevalence abstinence , 20.9 % versus 15.4 % ( OR = 1.45 , 95 % CI = 1.07 - 1.96 , P = 0.015 ) . CONCLUSIONS The results for the smokers are encouraging in showing a small but useful effect of the tailored letter on quit rate . Versions of the tailoring program could be used on the web and in general practice s , pharmacies and primary care trusts OBJECTIVE To compare the implementation , delivery , and implication s for dissemination of 2 different maternal smoking-cessation/relapse-prevention interventions in managed care environments . STUDY DESIGN Healthy Options for Pregnancy and Parenting ( HOPP ) was a r and omized , controlled efficacy trial of an intervention that bypassed the clinical setting . Stop Tobacco for OuR Kids ( STORK ) was a quasi-experimental effectiveness study of a point-of-service intervention . Both incorporated prenatal and postnatal components . PATIENTS AND METHODS Subjects in both studies were pregnant women who either smoked currently or had quit recently . The major intervention in HOPP was telephone counseling delivered by trained counselors , whereas the STORK intervention was delivered by providers and staff during prepartum , inpatient postpartum , and well-baby visits . RESULTS In HOPP , 97 % of telephone intervention participants reported receiving 1 or more counselor calls . The intervention delayed but did not prevent postpartum relapse to smoking . Problems with intervention delivery related primarily to identification of the target population and acceptance of repeated calls . STORK delivered 1 or more cessation contacts to 91 % of prenatal smokers in year 1 , but the rate of intervention delivery declined in years 2 and 3 . Modest differences were obtained in sustained abstinence between 6 and 12 months postpartum , but not in point prevalence abstinence at 12 months . CONCLUSIONS The projects were compared using 4 of the 5 dimensions of the RE- AIM model including reach , adoption , implementation , and maintenance . It was difficult to apply the fifth dimension , efficacy , because of the differences in study design and purpose of the interventions . The strengths and limitations of each project were identified , and it was concluded that a combined intervention that incorporates elements of both HOPP and STORK would be optimal if it could be implemented at reasonable cost BACKGROUND Tobacco dependence is a chronic condition requiring repeat treatment and long-term follow-up . However , current evidence regarding best approaches to providing these services is fairly limited . This study assessed the effectiveness of an intervention for increasing repeat tobacco-dependence treatment in a population of relapsed smokers . DESIGN The study was a multicenter r and omized controlled trial . SETTING / PARTICIPANTS Patients aged 19 and older receiving a prescription for nicotine replacement therapy or bupropion for smoking cessation in 2002 at one of five participating Veterans Affairs ( VA ) facilities were eligible . INTERVENTION A total of 1900 eligible veterans were r and omized to ( 1 ) patient phone call to assess smoking status , quit challenges , and treatment preferences , and computerized progress note to providers communicating this information ( intervention ) ; or ( 2 ) usual care ( control ) . MAIN OUTCOME MEASURES Outcomes , assessed in 2003 , included the proportion of patients receiving repeat pharmacologic or behavioral smoking-cessation treatment in the 6-month follow-up period ( assessed from VA pharmacy and outpatient data ) , 7-day point prevalence abstinence , and satisfaction ( assessed by patient survey ) . RESULTS Thirty-four percent of intervention participants versus 22 % of controls received treatment for tobacco dependence in the follow-up period ( p = 0.0001 ) . Thirty-two percent of intervention participants versus 21 % of controls received pharmacologic treatment ( p = 0.0001 ) , and 12 % of intervention subjects versus 8 % of controls received behavioral treatment ( p = 0.005 ) . Abstinence rates at follow-up were 25 % for intervention subjects and 22 % for controls ( p = 0.15 ) . Intervention subjects were more likely than controls to report being satisfied with the general smoking-cessation help ( 87 % vs 82 % , p = 0.01 ) , as well as the pharmacologic help that they received from the VA ( 89 vs 84 % , p = 0.01 ) . CONCLUSIONS The intervention significantly increased repeat treatment rates and satisfaction with services but did not have a significant effect on abstinence rates This cross-sectional study assessed changes between 1999 and 2003 in attitudes among Swedish general practitioners ( GPs ) toward smoking cessation activities and also assessed the effect of a nationwide quitline on GPs ' smoking cessation activities . A r and om sample of 621 Swedish GPs answered a question naire mailed to their home addresses in spring 2003 . When possible , the results of the present study were compared with results from a similar study conducted in 1999 . Main outcome measures were GPs ' self-reported activities , perceived barriers to engaging in smoking cessation , and referrals to the quitline . Between 1999 and 2003 , GPs increased their overall smoking cessation activities and were more aware of the complexity of smoking cessation support . Significantly more GPs experienced smoking cessation support as " too time consuming " and preferred to refer smokers to counselors specializing in smoking cessation . GPs referring patients to the quitline were more likely to be active in other smoking cessation activities . One out of five GPs had advised their patients to use oral smokeless tobacco as a means to stop smoking . A paradigm shift regarding awareness of the complexity of smoking cessation support may be ongoing amongst Swedish GPs . The nationwide smoking cessation quitline appears to have had a positive effect on GPs ' engagement in smoking cessation This correlational study examined the adherence rates of transdermal nicotine ( TN ) use among a population of males and females 18 years of age and older ( N = 619 ) who received varying levels of behavioral intervention . Rates of patch adherence were assessed for demographic ( e.g. , gender , ethnicity , and age ) , income- , smoking- [ e.g. , baseline carbon monoxide ( CO ) , nicotine dependence , and follow-up quit status ] , and treatment-related ( e.g. , condition , and drop status ) variables . Loglinear and logistic regression analyses were performed to assess adherence rates . Results indicated that male gender [ chi2(2 , n = 485 ) = 20.39 , P = .038 ] , not dropping out of the study [ chi2(2 , n = 485 ) = 13.94 , P < .001 ] , and intensive treatment ( compared to the st and ard care ) [ chi2(4 , n = 485 ) = 14.96 , P = .005 ] were associated with greater adherence to TN . Furthermore , patch adherence was associated with quit status at 6 months ( OR = 2.47 , CI = 1.56 - 3.91 , P < .001 ) and 12 months ( OR = 2.12 , CI = 1.34 - 3.37 , P = .001 ) . Complete and partial patch adherence ( compared to minimal/no adherence ) were associated with a greater number of telephone intervention contacts completed ( OR = 2.621 , CI = 1.421 - 4.832 , P = .002 ) . Noteworthy however , was the lack of association between level of income and patch adherence . These findings suggest characteristics of those more and less likely to adhere to TN in research and clinical setting We conducted a 2-arm r and omized trial to test the efficacy of self-help material s with or without proactive telephone counseling to increase cessation among teen smokers . Teen smokers ( N = 402 ) recruited from 11 shopping malls and 1 amusement park in the southeastern United States were r and omized to 1 of 2 groups : written self-help material plus video ; or written self-help material , video , and telephone counseling . Cessation rates based on 7-day point-prevalent abstinence for the self-help and counseling arms were 11 % and 16 % , respectively ( p = .25 ) , at 4 months postbaseline and 19 % and 21 % , respectively ( p = .80 ) , at 8 months postbaseline . Sustained abstinence , reflecting 7-day abstinence at both time points , in the self-help and counseling arms was 7 % and 9 % ( p = .59 ) . Results suggest that minimal self-help cessation approaches that target youth have comparable success to that shown among adult smokers . However , refinements in telephone-counseling approaches may be needed to achieve the success observed in adult population Background Although it is now generally accepted that patients should be advised to quit smoking before surgery , the effect of low-intensive smoking cessation intervention , both on preoperative smoking behavior and on risk reduction , remains unclear . Our objective was to study the effect on perioperative smoking behavior and on postoperative wound infection of different types of low-intensive intervention before herniotomy . Methods Between October 1998 and October 2000 , 180 consecutive smokers scheduled for elective herniotomy were advised to quit smoking perioperatively and subsequently allocated r and omly to three low-intensive smoking cessation groups : a st and ard ( control ) group , a telephone group , which was reminded by telephone , and an out-patient group , which was reminded by means of an out-patient talk and demonstration of nicotine replacement drugs . Spontaneous perioperative smoking behavior was recorded for 64 consecutive non-advised smokers . Postoperative wound infection was evaluated by independent assessors . Results Of the advised patients , 19 % ( 29/149 ) stopped smoking before surgery compared with 2 % ( 1/64 ) in the non-advised cohort ( P < 0.01 ) . In the st and ard group 13 % ( 6/48 ) quit smoking compared with 23 % ( 23/101 ) in the pooled telephone and outpatient group ( NS ) . In the last group 64 % ( 65/101 ) reduced or stopped smoking compared with 42 % ( 20/48 ) in the st and ard group ( P < 0.05 ) . Predictors of failed perioperative cessation of smoking were a CO breath-test at inclusion above 20 ppm ( OR : 0.11 ; 0.02–0 - 57 ) and low motivation to quit smoking ( OR : 0.25 ; 0.09–0.70 ) . Wound infection occurred in 6 % ( 13/213 ) and there was no difference between the groups . Conclusion Low-intensive smoking cessation intervention helps approximately one fifth of patients to stop smoking perioperatively . Patients who are reminded in addition to preoperative advice are more likely to stop or reduce smoking . Failure to stop smoking is greater if the patients are not motivated and if the CO breath test is high at the time of the preoperative advice BACKGROUND AND OBJECTIVE GPs are an important source of smoking cessation advice . This research examined whether a model encouraging GP referral of patients who smoke to a specialist service would be acceptable and effective for increased smoking cessation when compared with a model of in- practice management . METHODS The study design was cluster r and omized controlled trial . Practice s were r and omized to one of two interventions , at a rate of 1:2 : ( i ) st and ard in- practice GP management or ( ii ) referral to a quitline service . The main outcome measures were sustained abstinence of > or=1 month duration at 3-month follow-up and > or=10 months duration at 12 months , using intention to treat analysis . RESULTS At 3-month follow-up , patients in the referral condition were twice as likely to report sustained abstinence than those in the in- practice condition [ 12.3 % compared with 6.9 % ; odds ratio ( OR ) = 1.92 ( 95 % confidence interval ( CI ) 1.17 - 3.13 ] . At 12-month follow-up , patients in the referral condition had nearly three times the odds of sustained abstinence [ 6.5 % compared with 2.6 % ; OR = 2.86 ( 95 % CI 0.94 - 8.71 ) ] . The intervention effect was mediated by the amount of help received outside the practice . CONCLUSIONS This research provided evidence that GPs referring smokers to an evidence -based quitline service results in increased cessation . The benefit is largely due to patients in the referral condition receiving more external help than patients in the in- practice condition , as they received equivalent practice -based help . Where suitable services exist , we recommend that referral become the normative strategy for management of smoking cessation in general practice to complement any practice -based help provided BACKGROUND Brief clinician intervention and telephone counseling are both effective aids for smoking cessation . However , the potential benefit of telephone care above and beyond routine clinician intervention has not been examined previously . The objective of this study is to determine if telephone care increases smoking cessation compared with brief clinician intervention as part of routine health care . METHODS This 2-group , prospect i ve , r and omized controlled trial enrolled 837 daily smokers from 5 Veterans Affairs medical centers in the upper Midwest . The telephone care group ( n = 417 ) received behavioral counseling with mailing of smoking cessation medications as clinical ly indicated . The st and ard care group ( n = 420 ) received intervention as part of routine health care . The primary outcome was self-reported 6-month duration of abstinence 12 months after enrollment . Secondary outcomes were 7-day point prevalence abstinence at 3 and 12 months , participation in counseling programs , and use of smoking cessation medications . RESULTS Using intention-to-treat procedures , we found that the rate of 6-month abstinence at the 12-month follow-up was 13.0 % in the telephone care group and 4.1 % in the st and ard care group ( odds ratio [ OR ] , 3.50 ; 95 % confidence interval [ CI ] , 1.99 - 6.15 ) . The rate of 7-day point prevalence abstinence at 3 months was 39.6 % in the telephone care group and 10.1 % in the st and ard care group ( OR , 5.84 ; 95 % CI , 4.02 - 8.50 ) . Telephone care compared with st and ard care increased the rates of participation in counseling programs ( 97.1 % vs 24.0 % ; OR , 96.22 ; 95 % CI , 52.57 - 176.11 ) and use of smoking cessation medications ( 89.6 % vs 52.3 % ; OR , 7.85 ; 95 % CI , 5.34 - 11.53 ) . CONCLUSION Telephone care increases the use of behavioral and pharmacologic assistance and leads to higher smoking cessation rates compared with routine health care provider intervention Pharmacological interventions for smoking cessation are typically evaluated using volunteer sample s ( efficacy trials ) but should also be evaluated in population -based trials ( effectiveness trials ) . Nicotine replacement therapy ( NRT ) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New Engl and Veterans Affairs Medical Center . Telephone interviews were completed with 3,239 smokers , and 2,054 agreed to participate ( 64 % ) . Participants were r and omly assigned to one of four conditions : stage-matched manuals ( MAN ) ; NRT plus manuals ( NRT + MAN ) ; expert system plus NRT and manuals ( EXP + NRT + MAN ) ; and automated counseling plus NRT , manuals , and expert system ( TEL + EXP + NRT + MAN ) . Assessment s were completed at baseline , 10 , 20 , and 30 months . The point prevalence cessation rates at final follow-up ( 30 months ) were MAN , 20.3 % ; NRT + MAN , 19.3 % ; EXP + NRT + MAN , 17.6 % ; and TEL + EXP + NRT + MAN , 19.9 % . Stage-matched manuals provided cessation rates comparable with previous studies . The addition of NRT , expert system interventions , and automated telephone counseling failed to produce a further increase in intervention effectiveness This prospect i ve r and omized study examined the impact of three tailored intervention approaches to increase quitting rates among African-American smokers who were clients of a community health center that serves primarily low-income and indigent persons . Smokers were r and omized to one of three groups : ( 1 ) health care provider prompting intervention alone , ( 2 ) health care provider prompting intervention with tailored print communications , and ( 3 ) health care provider prompting intervention with tailored print communications and tailored telephone counseling . Among the 160 smokers who completed the study , 35 ( 21.8 % ) had quit smoking at follow-up . Smokers who received the provider prompting intervention with tailored print material s were more likely to report having quit than smokers who received the provider intervention alone ( 32.7 % vs. 13.2 % , p < 0.05 ) . Smokers who received all three intervention components were not more likely to report having quit at follow-up than those who only received the provider intervention ( 19.2 % vs. 13.2 % ) . Smokers who at baseline were less educated , smoked less than half a pack of cigarettes per day , had a stronger desire to quit , felt more efficacious , and had thought about quitting were more likely to report having quit at follow-up . These results provide support for continued refinement of tailored communications to aid smoking cessation among African-American smokers The effect of a smokers ' hotline as an adjunct to self-help manuals was examined . Subjects were 1,813 smokers recruited from a 10-county rural and small urban area . Counties were matched on demographic characteristics and assigned to a manual only or manual plus hotline condition . Subjects were followed over an 18-month period . Hotline services included taped messages and access to paraprofessional counselors . Results show a consistent , significant hotline effect across outcome measures and follow-up periods . This effect emerged either as a main effect for the hotline or as an interaction with enrollment method such that a significant hotline effect emerged for subjects who enrolled through face-to-face methods . These findings indicate the effectiveness of the hotline in enhancing self-help quit rates Objectives Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently , and thus may have limited access to worksite health promotion efforts . The objective of this study was to test a behavioral intervention among construction laborers . Methods Using a r and omized-controlled design , we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption ( n = 582 ) . Results At baseline , 40 % of control group participants and 45 % of intervention group participants reported using any tobacco in the last seven days . At final , 8 % of baseline cigarette smokers in the control group had quit , compared to 19 % in the intervention group ( p = 0.03 ) . In both groups , the mean consumption of fruits and vegetables at baseline was over five servings per day . At final , the intervention group had increased consumption by approximately one and one-half servings , compared to a slight decrease in consumption in the control group ( p < 0.001 ) . Conclusions A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers , a high-risk , mobile workforce OBJECTIVE Radon and cigarette smoking have synergistic effects on lung cancer , even when radon concentrations are relatively low . Working through an electric utility company , we sought to reach smoking households with low radon concentrations and motivate smoking cessation or prohibiting smoking in the home . DESIGN Eligible homes ( n = 714 ) were r and omised to receive : ( 1 ) the Environmental Protection Agency 's ( EPA 's ) “ A citizen 's guide to radon ” ; ( 2 ) a specially developed pamphlet ; or ( 3 ) that pamphlet plus brief telephone counselling . PROCEDURE Utility company “ bill stuffers ” offered free radon test kits to smoking households . All households received radon test results with an explanatory cover letter . Both the specially developed pamphlet and the telephone counselling emphasised that smoking cessation or prohibiting smoking in the home were the optimal risk reduction strategies . Households were followed up at 3 and 12 months after receiving material s. RESULTS The specially developed pamphlet and the EPA guide yielded similar outcomes . There was a non-significant trend for telephone counselling to produce greater sustained quitting than the specially developed pamphlet , and phone counselling led to significantly more new household smoking bans . CONCLUSIONS Working through a public utility company is an efficient way to reach smoking households , and brief telephone counselling is a promising method for promoting household smoking bans and cessation in homes alerted to the risk posed by the combination of radon and smoking Objectives : State and national tobacco quitlines have exp and ed rapidly and offer a range of services . We examined the effectiveness and cost effectiveness of offering callers single session versus multisession counselling , with or without free nicotine patches . Methods : This 3 × 2 r and omised trial included 4614 Oregon tobacco quitline callers and compared brief ( one 15-minute call ) , moderate ( one 30-minute call and a follow-up call ) and intensive ( five proactive calls ) intervention protocol s , with or without offers of free nicotine patches ( nicotine replacement therapy , NRT ) . Blinded staff assessed tobacco use by phone at 12 months . Results : Abstinence odds ratios were significant for moderate ( OR = 1.22 , CI = 1.01 to 1.48 ) and intensive ( OR = 1.29 , CI = 1.07 to 1.56 ) intervention , and for NRT ( OR = 1.58 , CI = 1.35 to 1.85 ) . Intent to treat quit rates were as follows : brief no NRT ( 12 % ) ; brief NRT ( 17 % ) ; moderate no NRT ( 14 % ) ; moderate NRT ( 20 % ) ; intensive no NRT ( 14 % ) ; and intensive NRT ( 21 % ) . Relative to brief no NRT , the added costs for each additional quit was $ 2467 for brief NRT , $ 1912 for moderate no NRT , $ 2109 for moderate NRT , $ 2641 for intensive no NRT , and $ 2112 for intensive NRT . Conclusion : Offering free NRT and multisession telephone support within a state tobacco quitline led to higher quit rates , and similar costs per incremental quit , than less intensive protocol Reduction of smoking may increase the likelihood of eventual smoking cessation among those not ready to quit . We describe the development and acceptance of a smoking-reduction intervention that integrates telephone counseling sessions with newsletters . A computer-assisted telephone interviewing program generates real-time-tailored counseling delivered by lay interviewers . Pilot participants ( n = 53 ) were adult smokers scheduled for outpatient procedures in a health maintenance organization , r and omized to intervention or a control condition ( quarterly mailings ) . Smoking levels were measured by self-report and biochemically . Among intervention participants continuing at 3 months , all but one rated their telephone support person positively on all dimensions . Counseling calls were ' about right ' in number , and newsletters were perceived as quite personal . Intervention recipients reported smoking significantly fewer mean cigarettes per day at 3 months than at baseline , and significantly fewer than control participants . Comparisons were non-significant under intent-to-treat analyses and on biochemical measures . The program was well received by out patients who were not ready to quit smoking , and was implemented successfully by telephone staff who had no previous smoking cessation counseling experience . An ongoing trial is evaluating effectiveness , cost and relationship to eventual cessation OBJECTIVES To investigate the effectiveness of telephone counselling as an adjunct to nicotine replacement therapy ( NRT ) by transdermal patch in smoking cessation . DESIGN R and omised controlled trial . PARTICIPANTS AND SETTING 854 smokers from New South Wales , aged 18 years and older , who had smoked at least 10 cigarettes per day for the past year and responded to newspaper advertisements between October 2001 and January 2002 ; the trial was conducted between October 2001 and August 2002 . INTERVENTIONS R and om allocation to either NRT alone or NRT plus telephone counselling ( 5 sessions spaced according to a relapse-sensitive call schedule ) . MAIN OUTCOME MEASURES Self-reported abstinence assessed by telephone question naires at 1 , 2 , 3 and 6 months : 28-day continuous abstinence at 3 and 6 months , and 90-day continuous abstinence at 6 months . RESULTS 28-day continuous abstinence rates among participants receiving telephone counselling were significantly greater than among those not receiving telephone counselling at both 3 and 6 months ( 31.6 % v 25.1 % ; P = 0.04 at 3 months ; and 30.1 % v 22.4 % ; P = 0.01 at 6 months ) . Similarly , 90-day continuous abstinence rates at 6 months were significantly greater for participants receiving counselling ( 26.7 % v 18.6 % ; P = 0.004 ) . CONCLUSION Telephone counselling as an adjunct to NRT increases abstinence rates beyond the use of NRT alone Background GPs often lack time to provide intensive cessation advice for patients who smoke . This study aim ed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse . Methods Adult smokers ( n = 318 ) attending 30 GPs in South Western Sydney , Australia were r and omly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice , written information and follow-up delivered by a nurse . Self-reported point prevalence abstinence at six and 12 months was compared between groups . Characteristics of patients who accepted and completed the intervention were investigated . Results Of 169 smokers r and omised to the intervention , 76 ( 45 % ) consented to referral . Compared with smokers in ' pre-contemplation ' , those further along the stage-of-change continuum were significantly more likely to consent ( p = 0.003 ) . Those further along the continuum also were significantly more likely to complete all four calls of the intervention ( OR 2.6 , 95 % CI : 0.8–8.1 and OR 8.6 , 95 % CI : 1.7–44.4 for ' contemplation ' and ' preparation ' respectively ) . At six months , there was no significant difference between groups in point prevalence abstinence ( intention to treat ) ( 9 % versus 8 % , p = 0.7 ) . There was no evidence of differential intervention effectiveness by baseline stage-of-change ( p = 0.6 ) or patient sex ( p = 0.5 ) . At 12 months , point prevalence abstinence in the intervention and control groups was 8 % and 6 % respectively ( p = 0.6 ) . Conclusion Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low . This trial did not demonstrate improved quit rates following the intervention . Future research efforts might better focus support for those patients who are motivated to quit . Australian Clinical Trials Registry Background Smoking is an important risk factor for cardiovascular disease ( CVD ) , and quitting is highly beneficial . Yet , less than 30 % of CVD patients stop smoking . Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease . Objective A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change . Method Participants ( N = 168 ) were r and omly assigned by cohorts to inpatient counseling with telephone follow-up , inpatient counseling , and usual care . The inpatient intervention consisted of a 1-hr counseling session , and the telephone follow-up included 6 calls during the first 2 months after discharge . The nursing intervention was tailored to the individual 's stage of change . End points at 2 and 6 months included actual and continuous smoking cessation rates ( biochemical markers ) and increased motivation ( progress to ulterior stages of change ) . Results Assuming that surviving patients lost to follow-up were smokers , the 6-month smoking abstinence rate was 41.5 % in the inpatient counseling with telephone follow-up group , compared with 30.2 % and 20 % in the inpatient counseling and usual care groups , respectively ( p = .05 ) . Progress to ulterior stages of change was 43.3 % , 32.1 % , and 18.2 % , respectively ( p = .02 ) . Stage of change at baseline and intervention predicted smoking status at 6 months . Discussion This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months , and progression to ulterior stages of change . The telephone follow-up was an important adjunct . It is , therefore , recommended to include such comprehensive smoking cessation programs within hospital setting s for individuals with CVD BACKGROUND Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children 's health problems associated with exposure to tobacco smoke . The pediatric clinic is a " teachable setting " in which to provide advice and assistance to parents who smoke . OBJECTIVE To evaluate a smoking cessation intervention for women . DESIGN Two-arm ( usual care vs intervention ) r and omized trial . SETTING Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle , Wash , area . INTERVENTION During the clinic visit , women received a motivational message from the child 's clinician , a guide to quitting smoking , and a 10-minute motivational interview with a nurse or study interventionist . Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit . PARTICIPANTS Self-identified women smokers ( n = 303 ) whose children received care at participating clinics . MAIN OUTCOME MEASURE Self-reported abstinence from smoking 12 months after enrollment in the study , defined as not smoking , even a puff , during the 7 days prior to assessment . RESULTS Response rates at 3 and 12 months were 80 % and 81 % . At both follow-ups , abstinence rates were twice as great in the intervention group as in the control group ( 7.7 % vs 3.4 % and 13.5 % vs 6.9 % , respectively ) . The 12-month difference was statistically significant . CONCLUSIONS A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers . The results encourage implementation of evidence -based clinical guidelines for smoking cessation in pediatric practice BACKGROUND The Agency for Healthcare Research and Quality ( AHRQ ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit . METHODS We conducted a r and omized , controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin ( four test sites , four control sites ) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period ( June 16 , 1999 , to June 20 , 2000 ) or the intervention period ( from June 21 , 2000 , to May 3 , 2001 ) . After collecting baseline data , staff at test sites implemented the intervention over a 2-month period . The intervention included a tutorial for intake clinicians , group and individual performance feedback for intake clinicians , use of a modified vital signs stamp , an offer of free nicotine replacement therapy , and proactive telephone counseling . Staff at control sites received only general information about the AHRQ Guideline . Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessment s. Hierarchical logistic regression models were used to estimate the odds ratios ( ORs ) for treatment assignment after adjustment for patient characteristics . All statistical tests were two-sided . RESULTS There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period . Among participants treated during the intervention period , those at test sites were more likely than those at control sites to report being abstinent at the 2-month ( 16.4 % versus 5.8 % ; adjusted OR = 3.3 , 95 % confidence interval [ CI ] = 1.9 to 5.6 ; P<.001 ) and 6-month ( 15.4 % versus 9.8 % ; adjusted OR = 1.7 , 95 % CI = 1.2 to 2.6 ; P = .009 ) follow-up assessment s and to report continuous abstinence , that is , abstinence at both 2 and 6 months ( 10.9 % versus 3.8 % ; adjusted OR = 3.4 , 95 % CI = 1.8 to 6.3 ; P<.001 ) . CONCLUSION Implementation of a guideline -based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers The incremental effects of ( a ) a self-help booklet alone , ( b ) self-help booklet with computer-generated personalized feedback , and ( c ) self-help booklet , personalized feedback , and outreach telephone counseling were evaluated in a population -based , nonvolunteer sample of smokers . Smokers ( N = 1,137 ) were identified through a telephone survey of a r and om sample of 5,903 enrollees in a health maintenance organization and r and omized to a no-treatment control group or 1 of the 3 intervention conditions . Smoking status was ascertained 3 , 12 , and 21 months postr and omization . Cotinine validation of self-reported cessation was obtained at the 12-month follow-up . Overall , the telephone counseling significantly increased smoking cessation at the 3-month follow-up , but not at 12 or 21 months . Among smokers who were precontemplative at baseline , telephone counseling significantly increased prevalent abstinence at 3 and 12 months and continuous abstinence at 21 months ( defined as self-reported abstinence at 3 , 12 , and 21 months ) This research estimated the costs and effectiveness of three different benefit design s for treating tobacco dependence : drugs only ( nicotine replacement therapy patch , nasal spray , inhaler , and Zyban ) ; drugs and counseling ( drugs and proactive telephone counseling ) ; and drugs if counseling ( drugs conditional on enrollment in counseling ) . A sample of 393 adult smokers enrolled in a California preferred provider organization was r and omly assigned to one of three study groups . After eight months , there were no significant increases in quit attempts or quit rates in the groups with covered drugs and counseling compared to the group with drug coverage only . Therefore , costs rose with no increase in quit rates when proactive telephone counseling was added to coverage of pharmacotherapy , regardless of benefit design Background : Smoking , alcohol use , and depression are interrelated and highly prevalent in patients with head and neck cancer , adversely affecting quality of life and survival . Smoking , alcohol , and depression share common treatments , such as cognitive behavioral therapy and antidepressants . Consequently , we developed and tested a tailored smoking , alcohol , and depression intervention for patients with head and neck cancer . Methods : Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers . Subjects were r and omized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications . Data collected included smoking , alcohol use , and depressive symptoms at baseline and at 6 months . Results : The mean age was 57 years . Most participants were male ( 84 % ) and White ( 90 % ) . About half ( 52 % ) were married , 46 % had a high school education or less , and 52 % were recruited from Veterans Affairs sites . The sample was fairly evenly distributed across three major head and neck cancer sites and over half ( 61 % ) had stage III/IV cancers . Significant differences in 6-month smoking cessation rates were noted with 47 % quitting in the intervention compared with 31 % in usual care ( P < 0.05 ) . Alcohol and depression rates improved in both groups , with no significant differences in 6-month depression and alcohol outcomes . Conclusion : Treating comorbid smoking , problem drinking , and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately . ( Cancer Epidemiol Biomarkers Prev 2006;15(11):2203–8 BACKGROUND St and ard , generic self-help material s have been largely ineffective as behavioral treatments for smoking cessation . In contrast , self-help programs tailored to the needs of specific smokers have shown promise in facilitating quitting . OBJECTIVE To evaluate the incremental efficacy of the Committed Quitters Program ( CQP ) , a set of computer-tailored material s offered to purchasers of nicotine polacrilex gum , compared with a briefuntailored user 's guide and audiotape , both as supplements to nicotine replacement therapy . METHODS We conducted a r and omized , open-label trial with 3 parallel arms . Subjects were smokers who purchased 2- or 4-mg nicotine polacrilex gum and called the CQP toll-free enrollment line . Three thous and six hundred twenty-seven subjects consented to participate in 1 of 3 study arms : ( 1 ) those receiving the CQP material s ( CQP group , n= 1,217 ) , ( 2 ) those receiving CQP material s and an outbound telephone call ( CQP + C group , n= 1,207 ) ; and ( 3 ) those receiving no supplemental intervention beyond the user 's guide and audiotape that were prepackaged with the nicotine polacrilex gum ( UG group , n= 1,203 ) . Twenty-eight-day continuous abstinence rates were assessed by telephone interviews at 6 weeks and 10-week continuous rates at 12 weeks into treatment . RESULTS Abstinence rates among respondents at the 6- and 12-week assessment s were significantly higher for the CQP ( 36.2 % and 27.6 % ) and CQP + C ( 35.5 % and 27.3 % ) groups compared with the UG group ( 24.7 % and 17.7 % ) at both intervals . The quit rates for the CQP and CQP + C groups were almost identical . CONCLUSIONS The CQP proved to be an effective behavioral treatment , enhancing quit rates over and above nicotine replacement therapy and a brief untailored written guide and audiotape BACKGROUND Tobacco quitlines offer clinicians a means to connect their patients with evidence -based treatments . Innovative methods are needed to increase clinician referral . METHODS This is a clinic r and omized trial that compared usual care ( n = 25 clinics ) vs a pay-for-performance program ( intervention ) offering $ 5000 for 50 quitline referrals ( n = 24 clinics ) . Pay-for-performance clinics also received monthly up date s on their referral numbers . Patients were eligible for referral if they visited a participating clinic , were 18 years or older , currently smoked cigarettes , and intended to quit within the next 30 days . The primary outcome was the clinic 's rate of quitline referral ( ie , number of referrals vs number of smokers seen in clinic ) . RESULTS Pay-for-performance clinics referred 11.4 % of smokers ( 95 % confidence interval [ CI ] , 8.0%-14.9 % ; total referrals , 1483 ) compared with 4.2 % ( 95 % CI , 1.5%-6.9 % ; total referrals , 441 ) for usual care clinics ( P = .001 ) . Rates of referral were similar in intervention vs usual care clinics ( n = 9 ) with a history of being very engaged with quality improvement activities ( 14.1 % vs 15.1 % , respectively ; P = .85 ) . Rates were substantially higher in intervention vs usual care clinics with a history of being engaged ( n = 22 clinics ; 10.1 % vs 3.0 % ; P = .001 ) or less engaged ( n = 18 clinics ; 10.1 % vs 1.1 % ; P = .02 ) with quality improvement . The rate of patient contact after referral was 60.2 % ( 95 % CI , 49.7%-70.7 % ) . Among those contacted , 49.4 % ( 95 % CI , 42.8%-55.9 % ) enrolled , representing 27.0 % ( 95 % CI , 21.3%-32.8 % ) of all referrals . The marginal cost per additional quitline enrollee was $ 300 . CONCLUSION A pay-for-performance program increases referral to tobacco quitline services , particularly among clinics with a history of less engagement in quality improvement activities Aims : The primary aim of our r and omised control trial ( RCT ) was to evaluate the relative efficacy of two dental office based interventions compared to usual care . One intervention consisted of a combination of dental practitioner advice to quit and proactive telephone counselling ( 3A ’s ) , and the other arm consisted of a dental practitioner delivered intervention based on the 5A ’s of the Clinical Practice Guideline ( 5A ’s ) . Method : 2177 tobacco using patients were enrolled from 68 dental practice s in Mississippi . We collected 3-month outcome data from 76 % ( n = 1652 ) of participants . Results : Smokers in the two intervention conditions quit at a higher rate than those in usual care ; χ2 ( 1 , n = 1381 ) = 3.10 , p<0.05 . Although not significant , more patients in the 5A ’s condition quit than those in the 3A ’s . Of patients in the 3A ’s Condition , 50 % reported being asked by their dentist or hygienists about fax referral to the quitline , and 35 % were referred . Quitline counsellors contacted 143 ( 70 % ) referred participants . Conclusion : These results suggest that there are both advantages and disadvantages to the use of quitlines as an adjunct to brief counselling provided by dental practitioners . Patients receiving quitline counselling quit at higher rates than those who did not ; however , only a small percentage of patients received counselling from the quitline . Therefore , it appears that dental professionals may be most effective in helping their patients to quit by regularly providing the 5A ’s plus proactively referring only those patients who are highly motivated to a quitline for more intensive counselling Smokers with smoking-related diseases who are hospitalized in rehabilitation centers should be offered smoking cessation . This is the first study evaluating whether telephone booster sessions after intensive inpatient treatment are an effective strategy . The present study was conducted in 13 rehabilitation centers for somatic disorders as a prospect i ve multicenter study with a r and omized treatment-control group design . We compared abstinence rates after hospital discharge from treatment that included a group smoking cessation program with ( treatment group ) and without telephone booster sessions ( control group ) . Data from 290 smokers were analyzed . After 6 and 12 months the treatment group achieved abstinence rates twice as high as those of the control group . Men profited more from telephone booster sessions than did women . Results indicated that telephone booster sessions were highly effective ( even ) after an inherently intensive group program during a hospital stay . Further research should focus on the special needs of women receiving telephone counseling BACKGROUND A partner 's provision of support and smoking status has been consistently associated with women 's likelihood of smoking cessation during pregnancy and relapse in postpartum . DESIGN A three-group r and omized controlled intervention trial was conducted in 1996 to 2001 , with 583 women and their partners r and omized to usual care ( UC ) , woman-only ( WO ) , or partner-assisted ( PA ) intervention . Follow-ups occurred at 28 weeks of pregnancy , and 2- , 6- , and 12-months postpartum . SETTING Womack Army Medical Center ( WAMC ) at Fort Bragg in Fayetteville , North Carolina . INTERVENTION Women in the UC condition received provider advice to quit and a self-help guide . The WO condition received UC components plus a late-pregnancy relapse prevention kit ( booklet and gift items ) and six counseling calls ( three in pregnancy and three postpartum ) initiated by a health advisor . Women in the PA condition received the WO intervention , and their partners received telephone counseling and a support guide emphasizing skills to help the woman build and maintain her confidence to quit smoking . Partners who smoked also received cessation aids and related counseling . MAIN OUTCOME MEASURE Seven-day self-reported abstinence from smoking at each follow-up . RESULTS Intent-to-treat analyses showed no significant differences by condition in women 's reports of abstinence at any follow-up . In late pregnancy , more partners were abstinent in the PA condition ( 15 % ) than in the UC condition ( 5 % ) , p = 0.02 . CONCLUSIONS Partner-assisted smoking-cessation interventions need further refinement . Influencing young couples ' support patterns may require more intensive and conjoint intervention . Partners who smoke could benefit from support for their cessation efforts OBJECTIVE : To assess how often pregnant and postpartum smokers use medications and how often obstetric providers recommend them . METHODS : We analyzed end-of-pregnancy and 3-month postpartum surveys of 296 pregnant smokers enrolled in a r and omized controlled trial of telephone counseling for smoking cessation that did not include medication . Patients were asked whether any obstetric provider discussed cessation medication and whether they had used medication . RESULTS : At end of pregnancy , 29.3 % of respondents reported discussing a cessation medication with their obstetric providers , more often nicotine replacement ( 26.5 % ) than bupropion ( 12.2 % ) ( P=.001 ) . Ten percent of trial respondents used a medication while pregnant ( 7.4 % nicotine replacement , 3.4 % bupropion , P=.023 ) . Obstetricians discussed medication with 29.4 % of smokers at the postpartum visit ; 14.3 % of postpartum smokers used medication . Contrary to guidelines , women who smoked more cigarettes per day or had already tried quitting during pregnancy were not more likely to use medication or to discuss medication with their provider . Medication use was associated with older age , more education , living with a partner , a previous birth , having an obstetric provider who discussed medication , and having private health insurance in a state whose Medicaid program did not cover cessation medications ( all P<.05 ) . CONCLUSION : Pregnant women are more reluctant to use cessation medications than clinical guidelines recommend . More pregnant smokers might use cessation medications if their obstetricians discussed them routinely and if health insurance covered their cost . LEVEL OF EVIDENCE : Background Providing information is an important part of st and ard care and treatment for acute myocardial infa rct ion in patients . Evidence exists indicating that acute myocardial infa rct ion patients experience an information gap in the period immediately after discharge from the hospital . The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infa rct ion after their discharge from hospital . Design and method A prospect i ve r and omized , controlled trial with a 6-month follow-up was conducted . A total of 288 patients were allocated to either an intervention group ( n = 156 ) or a control group ( n = 132 ) . The latter received routine post-discharge care . The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey . Secondary endpoints included smoking and exercise habits . Results In both groups , health-related quality of life improved significantly over time on most subscales . A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale ( P=0.034 ) after 6 months . No difference was found between the groups on the Mental Health Component Summary Scale . We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months ( P=0.004 ) . More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up ( P=0.055 ) . Conclusion A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients . Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infa rct ion AIM To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model ( TTM ) compared to st and ard self-help smoking cessation literature . DESIGN R and omized controlled trial . SETTING Sixty-five West Midl and s general practice s. PARTICIPANTS R and omly sample d patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed . INTERVENTIONS Responders were r and omized to one of four interventions . The control group received st and ard self-help literature . In the Manual intervention group , participants received the Pro-Change system , a self-help workbook and three question naires at 3-monthly intervals , which generated individually tailored feedback . In the Phone intervention group , participants received the Manual intervention plus three telephone calls . In the Nurse intervention group , participants received the Manual intervention plus three visits to the practice nurse . MEASUREMENTS Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence , 12 months after study commencement . FINDINGS A total of 9.1 % of registered current smokers participated , of whom 83.0 % were not ready to quit . Less than half of participants returned question naires to generate second and third individualized feedback . Telephone calls reached 75 % of those scheduled , but few participants visited the nurse . There were small differences between the three Pro-Change arms . The odds ratio ( 95 % confidence intervals ) for all Pro-Change arms combined versus the control arm were 1.50 ( 0.85 - 2.67 ) and 1.53 ( 0.76 - 3.10 ) , for point prevalence and 6-month abstinence , respectively . This constitutes 2.1 % of the TTM group versus 1.4 % of the control group achieving confirmed 6-month sustained abstinence . CONCLUSIONS There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small OBJECTIVE To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation . STUDY DESIGN A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care . METHODS The study was performed at 18 Veterans Health Administration ( VA ) sites in California . Participants were VA patients receiving primary care . We r and omly allocated 10 of 18 sites to receive the Telephone Care Coordination Program , which included simple 2-click referral , proactive care coordination , medication management , and 5 follow-up telephone calls . Each patient received a 30- to 45-minute counseling session from the California Smokers ' Helpline . Patients at control sites received usual care . RESULTS During 10 months , we received 2965 referrals . We were unable to reach 1156 patients ( 39 % ) , despite at least 3 attempts . We excluded 73 patients ( 3 % ) , and 391 patients ( 13 % ) were not interested . We connected the remaining 1345 patients ( 45 % ) to the Helpline . At 6-month followup , 335 patients ( 11 % of all referrals and 25 % of participating patients ) were abstinent . Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites ( 15.6 vs 0.7 in the prior month ) . CONCLUSIONS The program generated a large number of referrals ; almost half of the patients referred were connected with the Helpline . Long-term abstinence was excellent . These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination Smoking and hyperlipidemia are key risk factors result ing in peripheral arterial disease . These risk factors can be reduced when appropriate lifestyle changes are made , especially for patients less than 60 years of age . Therefore patient education regarding smoking cessation and healthy diet changes may positively impact the course of disease . The ability to make a lifestyle change is affected by ( 1 ) an individual 's belief that his or her behavior affects the condition and ( 2 ) the social support received from family , especially a primary caregiver . This pilot study compared two r and omized groups of patients with peripheral arterial disease for a 1-year period . The control group received the st and ardized teaching plan regarding smoking cessation and diet at the postoperative clinic visit . The experimental group received the st and ardized teaching plan in addition to quarterly telephone calls to reinforce smoking cessation and diet information . At the end of 1 year , both groups received follow-up telephone calls at the conclusion of the study for endpoint data collection . Specifically , this project investigated the following research statements : ( 1 ) Patients who receive periodic telephone follow-up will have greater compliance with the recommendations regarding smoking and diet than those who do not receive follow-up . ( 2 ) Patients whose caregivers are compliant with the recommendations regarding smoking cessation and diet will have significantly higher compliance themselves . The data were analyzed by using cross tabulation , sign test , and McNemar 's test for nonparametric data to measure mobility , overall perception of health , knowledge of risk reduction information , and compliance with the smoking cessation and low fat/cholesterol diet plan . The results of this pilot study revealed no significant differences between the control and experimental groups . Telephone reinforcement was not sufficient in this study to influence lifestyle change . However , st and ardized teaching improved diet scores in both groups . Differences were found between smokers and nonsmokers Objective : To assess the relative impacts of three physician-delivered smoking interventions in combination with follow-up contact from behavioral counselors . Design : R and omized controlled trial with pre-post measures of smoking rates . This paper reports six-month outcome data . Setting : Participants were recruited from among patients seen by 196 medical and family practice residents in five primary care clinics . Participants : Participants were 1,286 patients out of 1,946 eligible smokers approached . The patient group was 57 % female and 91 % white , had an average age of 35 years , and smoked , on average , slightly over one pack per day . Intervention : Physicians were trained to provide each of three interventions : advice only , brief patient-centered counseling , and counseling plus prescription of nicotine-containing gum ( Nicorette ™ ) . Half the patients received follow-up in the form of telephone counseling at three-monthly intervals from behavioral counselors . Measurements and main results : Changes in smoking behaviors were assessed by telephone interview six months after physician intervention . The differences in one-week point prevalence cessation rates among the physician interventions were significant ( p<0.01 ) : advice only , 9.1 % ; counseling , 11.9 % ; counseling plus gum , 17.4 % ; with no effect for telephone counseling . The time elapsed from physician encounter to initial quitting and the length of that period of abstinence also showed significant benefit of the counseling interventions . Patients receiving physician counseling were much more likely than those not receiving counseling to rate their physician as very helpful ( p<0.001 ) . Multiple regression analyses are also reported . Conclusion : Smoking intervention counseling provided by physicians is well received by patients and significantly increases the likelihood of cessation at six months , an effect that is augmented by the prescription of nicotine-containing gum , when compared with physician-delivered advice . Follow-up telephone counseling does not contribute significantly to smoking behavior changes BACKGROUND This study tested the effects of two organizational support processes , the provision of financial incentives for superior clinical performance and the availability of a patient ( smoker ) registry and proactive telephone support system for smoking cessation , on provider adherence to accepted practice guidelines and associated patient outcomes . METHODS Forty clinics of a large multispecialty medical group practice providing primary care services were r and omly allocated to study conditions . Fifteen clinics each were assigned to the experimental conditions " control " ( distribution of printed versions of smoking cessation guidelines ) and " incentive " ( financial incentive pay-out for reaching preset clinical performance targets ) . Ten clinics were r and omized to receive financial incentives combined with access to a central ized patient registry and intervention system ( " registry " ) . Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients ' smoking cessation behaviors . RESULTS Patients ' tobacco use status was statistically significant ( P < 0.01 ) more frequently identified in clinics with the opportunity for incentives and access to a registry than in clinics in the control condition . Patients visiting registry clinics accessed counseling programs statistically significantly more often ( P < 0.001 ) than patients receiving care in the control condition . Other endpoints did not statistically significantly differ between the experimental conditions . CONCLUSIONS The impact of financial incentives and a patient registry/intervention system in improving smoking cessation clinical practice s and patient behaviors was mixed . Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment This study evaluated the effects of including a single brief prequit telephone counseling session in a self-help program for smoking cessation conducted through the mail , by comparison with the effects of the self-help program alone . Volunteer participants from northwestern Spain ( N = 228 ) were r and omly assigned to one of two groups : ( a ) the self-help-only group ( n = 110 , mean age = 37.4 years , pretreatment cigarette consumption = 26.5 cigarettes/day ) or ( b ) the telephone-support group ( n = 118 , mean age = 36.8 years , pretreatment cigarette consumption = 27.7 cigarettes/day ) . Using a conservative data analysis method ( missing data considered as treatment failures ) , we found that the point-prevalence abstinence rate was significantly higher in the telephone-support group than in the self-help-only group at the end of treatment ( 44.9 % vs. 21.8 % ) and at the 3-month follow-up ( 39.0 % vs. 26.4 % ) . Likewise , sustained abstinence was significantly higher in the telephone-support group at the 3-month follow-up ( 33.9 % vs. 13.6 % ) , the 6-month follow-up ( 25.4 % vs. 12.7 % ) , and the 12-month follow-up ( 21.2 % vs. 9.1 % ) . The results of this r and omized controlled trial indicate that both treatments are an effective aid for smoking cessation , and that a single brief telephone call before the quit date is a low-cost and effective procedure for improving abstinence rates in a mailed self-help program OBJECTIVE We report on the process evaluation of an efficacious national smoking cessation intervention for adult survivors of childhood cancer . We examine associations between intervention implementation characteristics and study outcomes , as well as participant characteristics related to level of involvement in the intervention . METHODS The study was conducted at the Dana-Farber Cancer Institute in Boston , Massachusetts , from 1999 - 2001 . Participants ( n = 398 ) were r and omly assigned to receive a proactive telephone-based peer counseling intervention . They received up to 6 counseling calls , individually tailored and survivor-targeted material s , and nicotine replacement therapy ( NRT ) patches if they were prepared to quit smoking . RESULTS Forty-two percent of survivors participated in the maximum number of calls ( 5 - 6 ) , and 29 % of participants requested and received NRT . Total counseling time was an average of 51 min . Quit status at follow-up was related to intervention dose , and participants who received NRT were significantly more likely to make a 24-h quit attempt . Demographic variables ( females , White ) , higher daily smoking rate , poorer perceived health and moderate perceived risk of smoking were significantly related to greater intervention involvement . CONCLUSIONS A brief peer-delivered , telephone counseling intervention is an effective way to intervene with adult survivors of childhood cancer who are smoking . Findings from the process evaluation data ( call length and number , frequency , and spacing ) will inform future telephone counseling cessation programs AIMS The development of acceptable , widely available and effective smoking cessation methods is central to public health strategy for tobacco control . We examined the effectiveness of a telephone callback counselling intervention , compared to the provision of self-help re sources alone . METHODS Participants were 998 smokers calling a state-wide " Quitline " service r and omly allocated to either callback counselling or ordinary care . The callback condition consisted of a series of brief counselling calls at strategic times in addition to ordinary care . The number of calls varied according to caller needs , and most occurred generally just before the person 's quit day and in the week or two after it . The service was delivered by trained telephone counsellors . RESULTS At the 3-month follow-up , significantly more participants in the callback group ( 24 % ) reported that they were quit , compared to those in the usual care comparison group ( 13 % ) . The difference in point prevalence of smoking declined to 6 % by the 12-month follow-up . Using sustained abstinence there was a significant benefit of callback counselling at 12-month follow-up . Treating dropouts as smokers reduced the overall magnitude of the effects somewhat . The benefit of callbacks was to marginally increase quit attempts and to significantly reduce relapse . CONCLUSION Our findings are consistent with those of other studies demonstrating benefits of callback telephone counselling to facilitate cessation . Such counselling provides a flexible , relatively inexpensive and widely available form of cessation service . It appears to encourage a greater proportion of quit attempts and to reduce the rate of relapse among those quitting . Further research is required to determine ways to enhance effectiveness , particularly studies of how to reduce relapse Background Telephone counseling in chronic disease self-management is increasing , but has not been tested in studies that control for quality of medical care . Objective To test the effectiveness of a six-session outpatient telephone-based counseling intervention to improve secondary prevention ( behaviors , medication ) in patients with acute coronary syndrome ( ACS ) following discharge from hospital , and impact on physical functioning and quality of life at 8 months post-discharge . Design Patient-level r and omized trial of hospital quality improvement ( QI-only ) versus quality improvement plus brief telephone coaching in three months post-hospitalization ( QI-plus ) . Data : medical record , state vital records , patient surveys ( baseline , three and eight months post-hospitalization ) . Analysis : pooled-time series generalized estimating equations to analyze repeated measures ; intention-to-treat analysis . Participants Seven hundred and nineteen patients admitted to one of five hospitals in two contiguous mid-Michigan communities enrolled ; 525 completed baseline surveys . Measurements We measured secondary prevention behaviors , physical functioning , and quality of life . Results QI-plus patients showed higher self-reported physical activity ( OR = 1.53 ; p = .01 ) during the first three months , with decline after active intervention was withdrawn . Smoking cessation and medication use were not different at 3 or 8 months ; functional status and quality of life were not different at 8 months . Conclusions Telephone coaching post-hospitalization for ACS was modestly effective in accomplishing short-term , but not long-term life-style behavior change . Previous positive results shown in primary care did not transfer to free-st and ing telephone counseling as an adjunct to care following hospitalization OBJECTIVE To examine whether telephone counselling based on the stages of change component of Transtheoretical model of behaviour change together with educational material s could help non-motivated smoking parents of young children to cease . DESIGN R and omised controlled trial . SETTING Hong Kong Special Administrative Region , PR China . PARTICIPANTS 952 smoker fathers and mothers of Chinese children aged 5 years . INTERVENTION Participants were r and omly allocated into two groups : the intervention group received printed self-help material s and three-session telephone-based smoking cessation counselling delivered by trained counsellors ; the control group received printed self-help material s only . A structured question naire was used for data collection at baseline and at 1 , 3 and 6 month follow up . MAIN OUTCOME MEASURES The main outcome is 7 day point prevalence quit rate at 6 months ( defined as not smoking during the 7 days preceding the 6 month follow up ) determined by self reports . Other secondary outcomes were self reported 24 h point prevalence quit rate and self-reported continuous quit rate and bio-chemically vali date d quit rate at 6 months . RESULTS A total of 952 smoker fathers and mothers were r and omized to the intervention ( n = 467 ) and control ( n = 485 ) groups . Most were daily smokers ( 92.4 % ) and the mean number of cigarettes smoked per day was 14.5 ( SD = 8.9 ) . By using intention-to-treat analysis , the 7 day point prevalence quit rate at 6 month follow up was significantly greater in the intervention group ( 15.3 % ; 68/444 ) than the control group ( 7.4 % ; 34/459 ) ( P < 0.001 ) . The absolute risk reduction was 7.9 % ( 95 % confidence interval : 3.78 % to 12.01 % ) . The number needed to treat to get one additional smoker to quit was 13 ( 95 % CI : 8 - 26 ) . The crude odds ratio of quitting was 2.3(95 % CI : 1.5 - 3.5 ) . The adjusted odds ratio was 2.1 ( 95 % CI : 1.4 - 3.4 ) ( adjusted for age , number of years smoked , and alcohol dependency ) . CONCLUSION Proactive telephone counselling is an effective aid to promote smoking cessation among parents of young children AIMS To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol , tobacco and illicit drugs after discharge from residential treatment . DESIGN AND SETTING A r and omized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa , Kansas and Nebraska were matched and then r and omly assigned to the intervention or control condition . PARTICIPANTS Approximately 50 adult residents ( in patients ) from each site were followed for 12 months after treatment discharge . INTERVENTION Participating residents in the six intervention centers received a 4-part , individually tailored , smoking cessation program while those in the six control sites received usual care . FINDINGS Both moderate and heavy drinking rates were reduced in the intervention group . Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6-month ( OR = 1.59 , 95%CI : 1.09 - 2.35 ) and 12-month assessment ( OR = 1.84 , 95%CI : 1.28 - 2.92 ) . Illicit drug use rates were comparable . Effect of the intervention on tobacco quit rates was not statistically significant . CONCLUSIONS Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process . However , low-intensity tobacco interventions are unlikely to yield high tobacco quit rates BACKGROUND Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients . This r and omized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California . METHODS Patients were r and omly assigned to usual care ( n = 990 ) , nurse-mediated , behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact ( minimal intervention , n = 473 ) , or the same inpatient counseling with 4 postdischarge telephone contacts ( intensive intervention , n = 561 ) . The main outcome measure , smoking cessation rate , was corroborated by plasma cotinine determination or family confirmation , 1 year after enrollment . RESULTS At 1 year smoking cessation rates were 27 % , 22 % , and 20 % for intensive intervention , minimal intervention , and usual care groups , respectively ( P = .009 for intensive vs usual care ) . Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care ( odds ratios , 1.6 and 2.0 , respectively ) . CONCLUSIONS A multicomponent smoking cessation program consisting of physician advice ; in-hospital , nurse-mediated counseling ; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers . Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans Whereas telephone-based counseling has been found to be effective in supporting smokers interested in quitting smoking , it is not known whether proactive efforts to reach smokers receiving cessation medications will enhance their likelihood of successful quitting . We had an opportunity to test , in a health plan setting , an offer of telephone-based counseling with smokers identified from health plan records as recently filling a prescription for nicotine replacement therapy or bupropion . After we removed 31 members determined to be ineligible , 1,329 were r and omly allocated to receive an invitation either to telephone-based counseling ( n = 663 ) or to a control group ( n = 666 ) . On average , 7 days ( range = 3 - 15 days ) elapsed from the day of the prescription fill until the Center for Health Promotion began calling to invite members to participate in telephone counseling . The Center for Health Promotion was able to reach 49 % of those in the intervention group ( 323/663 ) . Of these members , 118 ( 37 % ) declined any participation . Therefore , in response to the proactive contact , 63 % ( 205/323 ) of those reached and 31 % ( 205/663 ) of those eligible participated in some smoking cessation counseling . At the 3-month follow-up , we observed an increased quit rate ( 33.1 % vs. 27.4 % ) among health plan members r and omized to telephone-based smoking cessation counseling . The results varied by gender and amount smoked . In addition , the variables associated with quitting in a multivariate logistic regression model included older age and using more than 30 days of medication Background —Although men hospitalized with cardiovascular disease ( CVD ) show high smoking-cessation rates , similar data for women are lacking . We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD . Methods and Results —In this r and omized controlled trial conducted from 1996 to 2001 , 277 women diagnosed with CVD ( mean age 61±10 years ) were r and omly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group ( UG ; n=135 ) or intervention group ( IG ; n=142 ) . Baseline histories were obtained , and interviews to ascertain self-reported smoking status occurred at 6 , 12 , 24 , and 30 months after hospitalization . The UG received strong physician ’s advice , a self-help pamphlet , and a list of community re sources . The IG received strong physician ’s advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside , with telephone contact at intervals after discharge . The groups were similar demographically and had smoked cigarettes for a median of 38 ( IG ) or 40 ( UG ) years . Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis , and risk differences between groups were determined . Time smoke-free was significantly greater for the IG than the UG ( P = 0.038 ) . Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG ( P > 0.15 at all times ) . Conclusions —Cognitive behavioral intervention result ed in longer average times to resumption of smoking , but in these 2 groups of older women with limited social and financial re sources , long-term success rates were similar . Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time OBJECTIVES Recruiting pregnant smokers into smoking cessation intervention trials is challenging . Changes in health care systems offer new opportunities to overcome many of the obstacles encountered by research ers attempting to address the significant harm from maternal smoking . Investigators could facilitate smoking cessation study recruitment by collaborating with health care systems that systematic ally collect patient smoking status and record it in a central ized , retrievable fashion . This paper reports the results of utilizing this novel approach and compares it with a typical de central ized practice -based recruitment strategy . METHODS The study was conducted at Massachusetts General Hospital , in Boston , Massachusetts , from 2000 to 2005 . Four hundred forty-two pregnant smokers were recruited for a r and omized controlled trial of telephone-delivered smoking counseling from two sources : a network-model managed care health plan and community-based practice s ( CBP ) . At the health plan , study recruitment was built on an existing system that permitted pregnant smokers to be identified central ly . At the CBPs , identification and referral systems had to be developed at each practice specifically for the study . The two strategies were compared on the efficiency of recruitment , characteristics of enrollees , and study outcome and process measures . RESULTS The health plan strategy generated referrals nearly twice as fast as the CBP strategy ( 30.4 vs. 17.0 per month ) , but because referrals were not timely , a large proportion of women from the plan were too advanced in pregnancy to be eligible to enroll in the study . As a result , the two strategies yielded a comparable enrollment rate . Participants from the health plan were older , better educated , less racially diverse , more likely to be living with the baby 's father , and less likely to have smokers in their environment . These differences were largely explained by the socioeconomic diversity of women recruited from the CBPs . Smoking cessation outcomes did not differ by recruitment source . CONCLUSIONS A recruitment strategy using a health plan 's central ized system was more efficient than a practice -based recruitment strategy at identifying potential study participants , but less efficient at generating study participants from the referrals received . Importantly , participants recruited by the two strategies differed by socioeconomic , but not cessation-related , characteristics . To date , recruiting pregnant smokers into intervention studies remains re source intensive and time consuming . Participant identification and recruitment will be greatly enhanced by health system innovations such as implementation of electronic medical records BACKGROUND Formal efforts to recruit smokers into cessation programs have failed to reach large segments of the smoking population . Telephone intervention may represent a viable strategy to promote smoking cessation . An even more promising approach may be a combination of brief telephone support and outreach to identified smokers . METHODS Telephone support for smoking cessation was provided to four identified smoker population s in Bloomington , Minn , one of three Minnesota Heart Health Program education communities . Smokers were r and omly assigned to an intervention consisting of two 15-minute telephone calls approximately 1 to 3 weeks apart or to a nonintervention control . RESULTS At the 6-month follow-up , a significant overall effect was found in favor of the intervention condition for both self-reported and cotinine-vali date d quitting . Differences between intervention and control conditions were no longer significant at 18 months . CONCLUSIONS Smokers ' receptivity to telephone intervention was at least moderately encouraging . The cost of intervention could be relatively low if trained volunteers initiated telephone calls . However , more intensive telephone intervention and support may be needed to produce lasting changes in smoking prevalence BACKGROUND Effective cessation services are greatly underutilized by smokers . Only about 1.5 % of smokers in Minnesota utilize the state-funded QUITPLAN Helpline . Substantial evidence exists on the role of social support in smoking cessation . In preparation for a large r and omized trial , this study developed and piloted an intervention for an adult nonsmoking support person to motivate and encourage a smoker to call the QUITPLAN Helpline . METHODS The support person intervention was developed based on Cohen 's theory of social support . It consisted of written material s and three consecutive , weekly , 20 - 30 minute telephone sessions . Smoker calls to the QUITPLAN Helpline were documented by intake staff . RESULTS Participants were 30 support people ( 93 % women , 97 % Caucasian , mean age 49 ) . High rates of treatment compliance were observed , with 28 ( 93 % ) completing all three telephone sessions . The intervention was ranked as somewhat or very helpful by 77 % of the support people , and 97 % would definitely or probably recommend the program . Five smokers linked to a support person called the QUITPLAN Helpline . CONCLUSIONS An intervention using natural support networks to promote smoker utilization of the QUITPLAN Helpline is both acceptable to a support person and feasible . A controlled r and omized trial is under way to examine the efficacy of the intervention BACKGROUND Radon and cigarette smoking have a synergistic , multiplicative effect on lung cancer rates . Smokers , and perhaps nonsmoking residents , of smoking households are at increased risk for lung cancer even when radon levels are relatively low . A behavioral risk reduction strategy emphasizing smoking cessation is proposed and data are presented from pilot studies and a short-term evaluation of a r and omized intervention trial . METHODS Pilot studies , including radon testing , interviews , question naires , and focus groups , led to a three-arm r and omized intervention trial comparing two kinds of written material s and telephone counseling . Smoking households were recruited by offering free radon test kits through an electric utility companies billing system . Three-month follow-up data were obtained by mail and phone . RESULTS Of an estimated 2,600 smoking households in the utility district , 1,220 requested a radon test kit , and 714 were r and omized into three treatment conditions . Brief phone counseling ( up to two short calls ) significantly increased smoking quit rates , compared to written material s only , and was also related to other risk reduction behaviors ( e.g. , household ban on smoking ) . CONCLUSIONS Offering free radon testing through a public utility billing system is an effective recruitment tool for reaching households at risk due to radon-smoking synergy . Brief telephone counseling is superior to written material s in reducing smoking and encouraging indoor smoking bans . Methods are needed to better inform smokers of their additional risk from exposure to even low levels of radon AIMS To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori . METHODS A single-blind r and omised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori . The intervention included regular , personalised text messages providing smoking cessation advice , support , and distraction . Maori text messages related to Maori language , support messages ( in Maori and English ) and information on Maori traditions . Text messaging was free for 1 month . After 6 weeks , the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up . RESULTS Participants included 355 Maori and 1350 non-Maori . Maori in the intervention group were more likely to report quitting ( no smoking in the past week ) at 6 weeks ( 26.1 % ) than those in the control group ( 11.2 % ) RR 2.34 , 95 % CI : 1.44 - 3.79 . There was no significant difference between the RR for Maori and that for non-Maori ( RR : 2.16 , 95%CI : 1.72 - 2.71 ) . CONCLUSIONS A mobile phone-based cessation programme was successful in recruiting young Maori , and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates . This shows clear potential as a new public health initiative Most former cigarette smokers in the United States have stopped without formal assistance . However , a large proportion of smokers desire and seek help other than by attending formal programs . It is important to recognize what factors are likely to influence the effectiveness of smoking cessation attempts among these persons . The authors report results of a prospect i ve cohort study of 1,552 smokers who called a stop smoking hotline to request self-help smoking cessation information . The participants were classified into three groups based on reports at the 6-month followup : 242 quitters , 497 recidivists , and 813 nonquitters . Baseline and followup data were used to evaluate three comparisons : quitters versus nonquitters , quitters versus recidivists , and recidivists versus nonquitters . Nonquitters appear to be less motivated and more doubtful of their abilities to quit successfully compared with the other two groups . Quitters appear to live in a supportive environment for smoking cessation . Heavier smokers are more hesitant to try to quit , but once they make an attempt they are as likely to succeed as lighter smokers , when other factors are kept constant . Efforts to promote environments supportive of smoking cessation are likely to result in a larger number of successful quitters . Similarly , efforts to strengthen motivation and belief in personal ability to quit are likely to encourage more nonquitters to attempt to stop smoking . Finally , it appears that some smokers need a previous quit attempt before they are able to maintain cessation successfully OBJECTIVE : To evaluate the relative effectiveness of two self-help smoking interventions as adjuncts to a self-help manual and telephone support service ( hotline ) for older smokers . DESIGN : Subjects were stratified on baseline variables and r and omised to one of two treatment conditions in a methods development study . SUBJECTS : 177 community-dwelling smokers aged 60 years and older . INTERVENTIONS : All subjects received a self-help manual and access to a smokers ' telephone hotline . Subjects also received either mailings ( Letters condition ) or counselling telephone calls ( Proactive condition ) at four and eight weeks after enrollment . MAIN OUTCOME MEASURES : Use of the hotline and prevalence of abstinence lasting at least 48 hours ( verified by a " significant other " ) were assessed at three and six months for the full sample . Seven-day abstinence was calculated for comparison with previous research . A sub sample of 91 subjects was followed up at 12 months . RESULTS : Overall abstinence rates for the two conditions were in the range of typical self-help interventions . Men were more likely to be abstinent than women at follow up at three and six months . A significant gender x treatment interaction was found , with abstinence rates higher for men in the Letters condition , and women in the Proactive condition . Hotline use was high , with nearly half of subjects calling by 12 months . CONCLUSION : Both interventions appear promising for older smokers , but may be differentially effective for men and women . Older smokers will use a hotline ; whether Letters and Proactive interventions can improve on manual and hotline effectiveness rates alone is being tested in a subsequent controlled trial Smokers ( N = 3,030 ) were r and omized to receive 1 of 3 interventions : ( a ) a self-help quit kit , ( b ) a quit kit plus 1 telephone counseling session , or ( c ) a quit kit plus up to 6 telephone counseling sessions , scheduled according to relapse probability . Both counseling groups achieved significantly higher abstinence rates than the self-help group . The rates for having quit for at least 12 months by intention to treat were 5.4 % for self-help , 7.5 % for single counseling , and 9.9 % for multiple counseling . The 12-month continuous abstinence rates for those who made a quit attempt were 14.7 % for self-help , 19.8 % for single counseling , and 26.7 % for multiple counseling . A dose-response relation was observed , as multiple sessions produced significantly higher abstinence rates than a single session . The first week after quitting seems to be the critical period for intervention OBJECTIVES This r and omized controlled trial assessed the efficacy of a smoking relapse prevention program featuring 3 postdischarge telephone contacts with subjects who had quit smoking on hospitalization . METHODS Patients were r and omly assigned to public health nurse-mediated behaviorally oriented in-patient counseling focused on relapse prevention ( control group , n = 49 ) , or the same inpatient counseling with postdischarge telephone contacts at 7 , 21 and 42 days after discharge ( intervention group , n = 57 ) . The main outcome measure , smoking cessation rate , was obtained from self-reports at 3 , 6 and 12 months after discharge . Smoking cessation at 12 months after discharge was confirmed by urinary nicotine concentration . RESULTS At 3 , 6 and 12 months smoking cessation rates were 83 % , 63 % and 56 % for the intervention group , and 76 % , 65 % and 51 % for control group . After adjustment for sex , age , having any complication , number of family members , smoking status on admission , strength of nicotine dependence and self confidence to quit smoking , the odds ratio of cessation among the intervention group were 1.46 ( 95 % confidence interval ( CI ) : 0.48 - 4.47 ) , 0.82 ( 95 % CI : 0.31 - 2.17 ) and 0.99 ( 95 % CI : 0.40 - 2.45 ) at 3 , 6 and 12 months after discharge , respectively . CONCLUSION This program had limited efficacy to maintain postdischarge smoking abstinence . We should re-consider the modality of smoking cessation program for relapse prevention among hospitalized patients UNLABELLED PRIMARY AIM : Examine the effectiveness of extended cognitive behavior therapy ( CBT ) in promoting longer-term smoking abstinence . DESIGN Open-label treatment phase followed by extended treatment phase . R and omization conducted prior to entry into open-label treatment phase ; analysis based on intention-to-treat to avoid threat of selection bias . SETTING Community smoking cessation clinic . PARTICIPANTS A total of 304 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . INTERVENTION Open-label ( 8 weeks ) : all participants received bupropion SR , nicotine patch , CBT . Extended treatment ( 12 weeks ) : participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support . MEASUREMENTS Seven-day point prevalence abstinence , expired-air carbon monoxide . RESULTS At week 20 follow-up , CBT produced a higher 7-day point prevalence abstinence rate : 45 % versus 29 % , P = 0.006 ; at 52 weeks the difference in abstinence rates ( 31 % versus 27 % ) was not significant . History of depression was a moderator of treatment . Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy ( P < 0.05 ) . CONCLUSION The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term . At present , the minimum duration of therapy is unknown Introduction . Effective smoking cessation treatment requires active patient engagement . This may be particularly important for rural smokers who have less access to smoking cessation re sources than others . This study describes long-term engagement in counseling for smoking cessation and factors associated with engagement . Methods . As part of a r and omized trial , 231 rural smokers received up to 6 telephone-based counseling sessions at 6-month intervals over 24 months . Engagement in treatment was categorized according to the number of counseling calls each interval . During the final 6-month interval , more than 60 % of continuing smokers remained engaged in treatment . Call completion varied over time ; while levels of engagement dropped after the first interval , many continuing smokers remained engaged throughout the study . Education , age , motivation , income , diabetes , and health insurance status were predictors of treatment engagement . Conclusion . This study demonstrates that smokers will remain engaged in long-term counseling design ed to address the chronic nature of nicotine dependence Smoking cessation counseling is an important element of tobacco control in the workplace , but it is not easy to persuade workers to stop smoking . We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al. , which consisted of one brief individual counseling session and 4 follow-up telephone calls . Two hundred and twenty-eight smokers who visited our center for an annual health checkup were r and omly divided into two group : 117 were assigned to the intervention group , and 111 were controls . Smoking status question naires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session . Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program . During the counseling session , carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking . Only those clients who set a quit date during their counseling sessions received follow-up telephone calls . It was easy to implement this program ( 15 to 20 minutes long ) during a health checkup . No significant differences were observed in the baseline characteristics of the two groups . The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group . The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group . In the intervention group , the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success , but other baseline characteristics were similar in those who quit smoking and those who did not . The effectiveness and easy applicability of this cessation program was proved in the present study . Further examinations in various setting s are expected to clarify the effectiveness of this program The purpose of this study was to evaluate the effect of a nurse-directed smoking cessation intervention for adults hospitalized in a small community hospital using a quasiexperimental , prospect i ve , longitudinal design with biochemical validation of self-reported tobacco abstinence . Sixty-eight in patients were assigned to either a control ( n = 30 ) or an intervention group ( n = 38 ) . The control group received smoking cessation literature . The intervention group received smoking cessation literature and a nursing intervention . Each member of the intervention group was r and omly assigned to a one or four telephone call subgroup for post discharge nurse follow-up at 3 months . Fifty-five participants completed the study . Smokers receiving the nurse-directed intervention were significantly more likely to be tobacco abstinent at 3 months ( n = 17 , 55 % ) than smokers in the control group ( n = 5 , 21 % ) . Within the intervention group , tobacco abstinence at 3 months was not significantly different between the one and four telephone call groups . For the total sample , smoking relapse was significantly higher for participants who lived with another smoker We evaluated gender differences in demographic , smoking history , nicotine dependence , transtheoretical , and perceived stress variables as predictors of smoking cessation . Participants ( n = 381 ) smoked at least 15 cigarettes per day and were motivated to quit . The outcome variable was 7-day abstinence at 1-year follow-up . Predictor variables included : age , education level , number of years smoking , cigarettes per day , quit attempts , nicotine dependence , stage of change , decisional balance , processes of change , self-efficacy , and perceived stress . Logistic regression analysis was used to derive predictive models for women and men . In women , lower scores for pre- and mid-treatment perceived stress significantly increased the likelihood of being abstinent at follow-up . For men , a higher level of education or number of quit attempts lasting > 24 hours in the past year , along with less frequent use of behavioural processes of change at baseline increased the probability of being abstinent at follow-up There is new evidence that smokers of all ages benefit from cessation of smoking . Although most older smokers , like younger smokers , prefer to quit on their own , at the time this project was started , there were no material s or programs targeted to older smokers . Using the literature , focus groups with older smokers and a national survey of older smokers , we created Clear Horizons , a self-help guide for older smokers , and a telephone counseling protocol tailored to the needs of older smokers ( age 50 - 74 ) . Smokers were recruited from around the United States and assigned r and omly to a control guide , Clearing the Air , Clear Horizons alone or Clear Horizons and two counselor calls . Follow-up of nearly 2000 smokers was conducted by telephone 3 , 6 , 12 and 24 months after delivery of the self-help guides . This report focuses primarily on results at 3 months because that was the measurement for reactions to the interventions . At the 3 month interview , those in the tailored interventions rated their guides more highly than did those in the control group . They also read more of their guides and were more likely to reread them . Quit rates were significantly higher among smokers who received a combination of the tailored guide and telephone counseling . At 3 months , the combination of the guide and telephone counseling was most effective in helping smokers to quit . By 12 months , both the tailored guide alone and the tailored guide and calls groups had higher quit rates than the control guide but were not statistically different from one another OBJECTIVES The present study used telephone support both to sustain abstinence and to encourage renewed quit attempts in smokers who had completed an intensive smoking cessation clinic . METHODS Subjects were hard-core smokers ( n = 1083 ) who had attended a multisession cessation clinic . They were then assigned r and omly to receive telephone support ( intervention calls 3 , 9 , and 21 months after the targeted cessation clinic quit date ) or no further intervention . RESULTS In the intervention condition , subjects who relapsed were significantly more likely to resume abstinence ( that is , to recycle ) than those in the comparison condition at follow-up ( 6 months : 17.8 % vs 11.3 % ; 24 months : 25.7 % vs 18.2 % ) . Telephone support was not effective in preventing relapse , and overall differences in abstinence outcome were not significant . CONCLUSIONS The major hypothesis of the current study --that telephone support would enhance the resumption of abstinence -- received partial support . However , there was no evidence either of an overall treatment effect or of an effect in preventing relapse . Telephone outreach may be more effective in the context of self-help or other less intensive interventions AIM To evaluate the effectiveness of repeated-contact proactive telephone counselling for smoking cessation in a UK setting . DESIGN R and omized controlled trial . SETTING The Quitline , an established national telephone counselling service available throughout the UK . PARTICIPANTS AND INTERVENTION A total of 1,457 callers to the Quitline in 2000 and 2001 were allocated r and omly to a Control group to receive usual care or to a Repeated Contact group to be offered five proactive calls in addition to usual care . MEASUREMENTS Prolonged abstinence and 24-hour point-prevalent abstinence 6 and 12 months after recruitment , quit attempts and 24-hour periods of abstinence in non-quitters . FINDINGS No significant differences were found between the Repeated Contact and Control groups on prolonged or point-prevalent abstinence . On an intention-to-treat basis , 9.5 % of the Control group were abstinent for longer than 6 months at the 12-month follow-up , compared with 9.3 % of the Repeated Contact group ; 18.9 % and 20.2 % , respectively , were point-prevalent abstinent at the 6-month follow-up . Significantly more non-quitters in the Control group made a quit attempt in the first 6 months following recruitment than in the Repeated Contact group ( 62.6%/56.1 % , P < 0.05 ) . CONCLUSIONS Proactive telephone counselling did not significantly increase abstinence rates , and appeared to decrease quit attempts , in callers to the Quitline . A non-structured , client-led counselling protocol and insufficient pre-quit motivational counselling could account for the lack of effect OBJECTIVE To examine patient response to a smoking cessation program that combined a nicotine replacement system ( patch ) with telephone support . DESIGN R and omized trial . SETTING A large Midwestern HMO . PARTICIPANTS . Five hundred and nine smokers who attended orientation sessions where an overview of the study and the use of the nicotine patch was presented . INTERVENTION All subjects received a prescription for a nicotine replacement patch ( Prostep , Lederle Laboratories , Wayne , NJ ) . Participants were r and omly assigned to one of three intervention groups . Group I participants ( n = 166 ) received no additional support . Group II participants ( n = 167 ) were registered with a 24-hour telephone hotline . Group III participants ( n = 167 ) were registered with the 24-hour telephone hotline and received four follow-up telephone calls from health educators . OUTCOME MEASURE The primary outcome measure was smoking cessation . Subject satisfaction with study components was also evaluated . RESULTS Overall , there was no significant difference by group in smoking cessation rates : 20 % of patients in all three groups were smoke-free after 12 months . Few patients ( 1 % ) used the telephone hotline . The telephone follow-up did not have an impact on cessation rates , and most patients ( 92 % ) reported that the orientation session was useful . CONCLUSIONS The study experience has helped the HMO evaluate various study components and has had an impact on currently used telephone intervention strategies and educational material Relatively little research has been done to test quitsmoking interventions in African-American population s ? Cigarette smoking is integral to higher rates of cancer and cardiovascular morbidity and mortality for AfricanAmericans compared with their non-African-American counterparts in the United States . 2 African-American women smokers , in particular , may experience increased health risks related to cigarette smoking because they are reported to have higher average levels of cotinine , a nicotine metabolite , than other race or gender groups ? Homogeneity in economic , cultural , and social characteristics between client and provider has been identified as important in increasing the likelihood of success in quitsmoking programs . 2 Because of this , efforts to recruit and train facilitators from the African-American community could improve intervention effectiveness ? The purpose of this study was to evaluate the feasibility and effect of a behavior-change smoking-cessation intervention mailed in four weekly segments supplemented with weekly telephone support calls from an African-American woman ex-smoker , and to compare the effects to an advice-only intervention Self-help methods are preferred by smokers over clinic-based treatments providing more traditional services . Unfortunately , these more popular methods have not been extremely successful in getting smokers to quit . The poor success rates may be partially related to the lack of structure inherent in these treatment approaches . The present study examined a self-help program delivered to smokers via a written manual and limited duration phone calls -- the latter to add structure to the treatment procedures . The results , a 23 % abstinent rate , indicate that this approach has some promise for treating chronic smokers BACKGROUND Telephone quitlines are utilized by diverse individuals and represent an effective tobacco-cessation modality . Quitlines allow tobacco users to seek support for multiple quit attempts . Little is known about how frequently tobacco users take advantage of this opportunity . No studies have been conducted to determine how communication strategies affect quitline re-enrollments . This study aim ed to determine the rates of quitline re-enrollment and to compare the responses of people of varying racial/ethnic identities to invitations utilizing different communication strategies . DESIGN Four-cell RCT . SETTING / PARTICIPANTS R and om sample of 2400 tobacco users who enrolled into services during 2006 , with oversampling of ethnic population s. INTERVENTION Between November 2006 and January 2007 , participants received either no invitation to re-enroll or were invited to re-enroll into services via a letter , a letter with ethnic-specific content , or a letter and a telephone call . MAIN OUTCOME MEASURES Re-enrollment into quitline services . RESULTS Analysis of the 252 days prior to the intervention result ed in a spontaneous re-enrollment rate of 0.54 % per 30 days . Recruitment using mailers did not significantly change this rate ; the addition of telephone calls increased re-enrollment to 6.93 % per 30 days . No significant differences were found among the sub population s studied . Invalid addresses ( 16 % ) ; invalid telephone numbers ( 29.1 % ) ; and the inability to reach subjects after five call attempts ( 37.9 % ) were barriers to recruitment . CONCLUSIONS For those who have previously called quitlines for help , proactive re-enrollment can be one way to initiate a new quit attempt after relapse . This study has shown that it is feasible to re-enroll former quitline participants , making the test of effectiveness the next logical step BACKGROUND Although office-based and telephone support services enhance the rate of smoking cessation in managed care systems , it is not clear whether such services are effective for very low-income smokers . We evaluated the comparative effectiveness of usual care ( physician-delivered advice and follow-up ) and usual care enhanced by 6 computer-assisted telephonic-counseling sessions by office nurses and telephone counselors for smoking cessation in very low-income smokers in Medicaid managed care . METHODS A r and omized clinical trial comparing the 2 approaches was conducted in 3 Michigan community health centers . All clinicians and center staff received st and ard training in usual care . Selected nurses and telephone counselors received special training in a computer-assisted counseling program focusing on relapse prevention . RESULTS The majority of the study population ( 233 adult smokers with telephones ) were white ( 64 % ) women ( 70 % ) with annual incomes of less than $ 10,000 ( 79 % ) and with prescriptions of nicotine replacement therapy ( > 90 % ) . At 3 months , quit rates ( smoke-free status verified by carbon monoxide monitors ) were 8.1 % in the usual-care group and 21 % in the telephonic-counseling group ( P=.009 ) by intention-to-treat analysis . Special tracking methods were successful in maintaining participants in treatment . CONCLUSIONS Smoking cessation rates are enhanced in a population of very low-income smokers if individualized telephonic-counseling is provided . State and Medicaid managed care plans should consider investing in both office-based nurse and central ized telephonic-counseling services for low-income smokers Although smoking prevalence in the United States has declined markedly in recent years , prevalence among blue-collar workers remains high and few successful methods of reaching this group have been identified . The present study was design ed to test the relative efficacy of two different approaches to telephone smoking-cessation counseling for blue-collar workers . Our study built on the experience of the National Cancer Institute 's Cancer Information Service ( CIS ) and compared the past CIS smoking-cessation counseling procedure and a modified version of the present procedure . In our trial , callers to a special telephone hotline who asked for information on smoking cessation were r and omly assigned to receive counseling under one of two protocol s : 1 ) the past CIS procedure , in which general information was given and cessation material s were sent to the callers , and 2 ) a version of the present CIS stage-model procedure , adapted by us for use with blue-collar workers , in which callers were given counseling specific to their stage in the smoking-cessation process . The general-information group contained 185 subjects ; the stage-model group contained 197 . Despite extensive efforts in the present study , it was not possible to recruit the number of blue-collar workers planned for our statistical analysis . Consequently , of a total of 382 subjects recruited , 93 ( 24.3 % ) were blue-collar workers , 181 ( 47.4 % ) were white-collar workers , and 108 ( 28.3 % ) were retired persons who worked part time , student workers , or the unemployed . Our results show no statistically significant differences in either short-term or long-term nonsmoking rates between the general-information group and the stage-model group . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Little is known about the effectiveness of bupropion SR for smoking cessation outside the context of clinical efficacy trials , where in-person screening and treatment occur at a higher level than provided in a typical health care system . This article describes the methods for recruitment , screening for exclusions , and result ing sample in a field trial of bupropion SR undertaken in a managed-care setting . METHODS A total of 2979 telephone interviews were conducted to screen and identify eligible volunteers using a detailed protocol that allowed for consultation with study physicians when necessary . The volunteers ' primary care physicians were given the option to override their eligibility , and pharmacy data bases were used to verify medication reporting . RESULTS A total of 1909 ( 64 % ) volunteers were considered eligible for the study . The most common reason for exclusion was use of contraindicated medications ( 32 % ) , followed by recent use of one of the behavioral cessation programs ( 14 % ) , brain injury that reduced seizure threshold ( 14 % ) , current depression ( 14 % ) , and high levels of alcohol use ( 13 % ) . CONCLUSIONS The methods used in this field trial show that it is possible to enroll subjects in an effectiveness trial that is successful from the st and point of the consumer , provider , and health care system BACKGROUND African Americans remain a critically underserved group for smoking cessation interventions . This study tested the effectiveness of a tailored , culturally sensitive intervention for African American smokers who called the NCI Cancer Information Service ( CIS ) for help to quit smoking . METHODS This paper presents results of a 2-year study of tailored counseling strategies among African American smokers ( n = 1,422 ) who called four regional CIS offices in response to a radio-based media campaign in 14 communities . Callers were r and omly assigned to receive either the st and ard CIS quit smoking counseling and guide ( Clearing the Air ) or counseling and a guide ( Pathways to Freedom ) tailored to the quitting needs and barriers of African American smokers . Callers were predominantly female ( 63.6 % ) . ages 20 - 49 ( 88 % ) , with a high school education or more ( 84 % ) . Median smoking history was 17 years ; median smoking rate was 20 cigarettes/day . St and ard ( n = 689 ) and Tailored ( n = 733 ) group subjects did not differ on most baseline measures . RESULTS On most measures , St and ard and Tailored counseling/guides received similar ratings , but the Tailored guide was rated as having more appealing photos ( P = 0.001 ) and as being more appropriate for family members ( P = 0.003 ) . Six-month follow-up with 893 subjects ( response rates were 63 % St and ard , 62 % Tailored , ns ) showed significantly more quit attempts ( P = 0.002 ) and greater use of prequitting strategies ( P < 0.05 ) among Tailored than among St and ard subjects , but no differences in self-reported 1-week abstinence ( 14.4 % St and ard , 16.2 % Tailored ) ( ns ) . An opportunistic 12-month follow-up of subjects recruited in the last year of the study ( n = 445 ) ( response rates were 57 % St and ard , 60 % Tailored , ns ) showed a significantly higher quit rate ( 15.4 % St and ard , 25.0 % Tailored ) for Tailored subjects ( P = 0.034 ) . CONCLUSIONS Results show promise for tailored approaches to boost quit attempts and success rates among African American smokers Several studies have tested the effectiveness of telephone counseling as a smoking cessation intervention , but few have addressed its application with the special population of smokers who are also problem drinkers or recovering alcoholics . Two hundred and eighty-eight male and female subjects were recruited from six residential alcohol treatment programs in Nebraska , Iowa , and Kansas to receive three postreatment telephone calls based on the stages of change model . Most subjects ( 71 % ) participated in at least one telephone counseling session , but only 38 % participated in all three . Those who completed of session were significantly ( p < .01 ) more likely to have advanced one stage of change in their readiness to quit smoking and to report having quit smoking for at least 24 hours since leaving treatment ( p < .01 ) . Stage-based telephone counseling appears to be a feasible approach to addressing smoking cessation among recovering alcoholics , with a modest positive effect on subsequent tobacco use OBJECTIVE : Reducing tobacco use in pregnancy is a public health priority . Brief smoking counseling during prenatal care is effective but generates modest cessation rates . Telephone counseling is an effective smoking cessation method that could offer pregnant women convenient access to more intensive smoking cessation counseling . METHODS : The efficacy of proactive pregnancy-tailored telephone counseling for smoking cessation was compared with a “ best- practice ” brief-counseling control in a r and omized controlled trial of 442 pregnant smokers referred by prenatal providers and a managed care plan . Trained counselors using cognitive-behavioral and motivational interviewing methods called intervention subjects throughout pregnancy and for 2 months postpartum ( mean = 5 calls , mean total contact = 68 minutes ) . Controls received one 5-minute counseling call . RESULTS : Cotinine-vali date d 7-day tobacco abstinence rates in intervention and control groups were 10.0 % and 7.5 % at end of pregnancy ( odds ratio [ OR ] 1.37 , 95 % confidence interval [ CI ] 0.69–2.70 ; number needed to treat = 40 ) and 6.7 % versus 7.1 % at 3 months postpartum ( OR 0.93 , 95 % CI 0.44–1.99 ) . The intervention increased end-of-pregnancy cessation rates among 201 light smokers ( < 10 cigarettes/day at study enrollment ) ( intervention 19.1 % versus control 8.4 % ; OR 2.58 , 95 % CI 1.1–6.1 ; number needed to treat = 9.3 ) and among 193 smokers who attempted to quit in pregnancy before enrollment ( intervention 18.1 % versus control 6.8 % ; OR 3.02 , CI 1.15–7.94 ; number needed to treat = 8.8 ) ; 63 % of the sample ( n = 267 ) was in one of these subgroups . CONCLUSION : Proactive pregnancy-tailored telephone counseling did not outperform a brief “ best practice ” intervention among pregnant smokers . The intervention had efficacy in light smokers and in women who had attempted cessation earlier in pregnancy . Future studies should confirm whether telephone counseling benefits these groups of pregnant smokers . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , # NCT00181909 . LEVEL OF EVIDENCE : OBJECTIVE Well-documented challenges have hampered both intervention development and research in teen smoking cessation . Addressing these challenges , the Hutchinson Study of High School Smoking ( HS Study ) , the largest group-r and omized trial in adolescent smoking cessation to date , incorporates several design innovations to investigate the effect of a counselor-initiated , individually tailored telephone counseling smoking cessation intervention for older adolescents . This paper presents and discusses these innovative design features , and baseline findings on the result ing study population . METHOD The trial used a population -based survey to proactively identify and recruit all high school juniors who had smoked in the past month - potentially exp and ing intervention reach to all smokers , even those who smoked less than daily and those not motivated to quit . For ethical and intervention reasons , some nonsmokers were enrolled in the intervention , also . Other important design features included the r and om allocation of schools into experimental conditions ( intervention vs. no-intervention control ) and a multi-wave design . RESULTS AND CONCLUSION The design innovations address problems and challenges identified in adolescent smoking cessation literature . The heterogeneous baseline characteristics of the study population , well-balanced between the two arms , have three significant implication s : They ( 1 ) demonstrate the effectiveness of the trial 's design features , ( 2 ) highlight several intervention-related issues , and ( 3 ) provide assurance that the trial 's evaluation of intervention effectiveness will be unbiased Table . SI Units Systematic modification of coronary risk factors is not integrated into the medical care provided to most of the more than 1 million patients treated annually in the United States for acute myocardial infa rct ion by percutaneous transluminal coronary angioplasty or coronary artery surgery . Most of such patients have lipoprotein abnormalities [ 1 ] , and nearly one half smoke [ 2 ] . These risk factors , which contribute to subsequent morbidity and mortality , remain highly prevalent after acute cardiac events . Failure to integrate comprehensive risk factor modification into the st and ard medical care provided to patients after acute cardiac events primarily reflects the lack of an organizational framework or system . This deficiency in re source allocation for preventive and rehabilitative aspects of care in turn reflects the predominant orientation of the U.S. health care system to the management of acute illness [ 3 ] . Several clinical research studies have shown the effectiveness of risk factor modification , especially treatment of lipoprotein abnormalities [ 4 - 7 ] , in achieving regression of coronary artery lesions and reducing the clinical consequences of coronary artery disease [ 6 , 7 ] . However , risk factor interventions shown to be effective in clinical trials may not prove equally effective in clinical practice because of a paucity of re sources , especially nonphysician personnel . The lack of effective management systems limits the expected reduction in morbidity and mortality and the corresponding reduction in medical care costs that motivates current efforts to orient the priorities of the American health care system toward preventive and rehabilitative care . This r and omized , controlled trial compared the effectiveness of a physician-directed , nurse-managed , home-based case-management system for coronary risk factor modification with that of usual medical care . Outcomes were measured in both groups immediately after the end of the first year after acute myocardial infa rct ion . The term case-management system has been used in various context s. As used here , it refers to a system in which a nurse case-manager , working with different health care specialists ( a psychiatrist , a cardiologist , a lipid specialist , a nutritionist , and a nurse coordinator ) , managed coronary risk factors . Methods Enrollment and Orientation Program nurses enlisted patients on hospital day 3 or as soon as their medical condition stabilized . Study participants gave written informed consent to be r and omly assigned to a treatment group . Immediately after r and omization , program nurses introduced patients to the special intervention with the aid of a videotape . Usual Care The 585 patients in our study were cared for by 215 internists and 34 cardiologists in the five participating medical centers who were organized into practice groups of 5 to 10 physicians each . Cardiology consultation was often provided during hospitalization , but primary responsibility for follow-up care was generally assumed by internists . The usual care offered by the Kaiser Permanente Medical Care Program included physician counseling on smoking cessation and nutritionist counseling on dietary change during hospitalization and physician-managed , lipid-lowering drug therapy after hospital discharge . Group outpatient smoking cessation programs were available for a $ 50 fee . Group exercise rehabilitation , not generally provided by the Kaiser Permanente Medical Care Program during this study , was available to patients at various community facilities at an average cost of $ 1800 to $ 2700 for 3 months ' participation . Special Intervention The behavioral interventions in our case-management system , which were offered to the 293 patients in the intervention group in addition to usual care , were derived from social learning theory [ 8 , 9 ] and modified for medical problems [ 10 ] . In this model , persons must learn how to monitor the health habits they seek to change , set attainable sub goals to motivate and direct their efforts , use feedback of progress in ways that promote health , and enlist incentives and social support to sustain the effort needed to succeed [ 8 , 9 ] . In the hospital , patients were instructed on how to complete self-reports [ status reports ] of smoking , dietary intake , and exercise . Scheduled interactions between case managers and patients after discharge took three forms : 1 ) nurse-initiated telephone contacts ; 2 ) computer-generated progress reports mailed to patients based on question naires completed by patients and mailed to the nurses ; and 3 ) visits to the program nurse for treadmill exercise testing , initiation of lipid-lowering drug therapy , if indicated , and a single counseling session after a smoking relapse . The maximum number of treatment contacts during the year , including outcome measurement at 6 and 12 months , was as follows : 14 nurse-initiated telephone contacts , 8 patient visits to the blood chemistry laboratory , and 4 patient visits to the nurse case manager . Smoking Intervention Smoking was defined as the use of cigarettes , cigars , cigarillos , pipe tobacco , or any other form of tobacco in the 6 months before admission . Forty-three percent of patients were smokers . Patients who had smoked during the 6 months before hospitalization received the same intensive smoking cessation intervention during hospitalization ; this intervention has been described previously [ 11 ] . Physicians used a written script that enabled them to provide st and ardized counseling in less than 2 minutes . The hospital-based smoking cessation counseling focused on relapse prevention . Nurses conducted a st and ardized smoking history to evaluate patients ' addiction to smoking . Patients ' reported self-efficacy or confidence to resist smoking in each of 28 potentially high-risk situations was measured ; patients were then counseled on how to manage the situations in which they reported less than 70 % confidence . Patients also received a relapse prevention manual and a relaxation audiotape . They were advised that the nurse would telephone them 48 hours and 1 week after hospital discharge and at monthly intervals for as long as 6 months . Patients who relapsed were offered one additional visit with the nurse for further counseling . Nicotine polacrilex or transdermal nicotine patches were reserved for highly addicted patients who relapsed after hospital discharge . Nutritional Counseling A computer-based expert system developed by the investigators was used to provide nutritional counseling on a National Cholesterol Education Program [ 12 ] Step 2 diet that was low in cholesterol and saturated fat . A food frequency question naire design ed by the investigators was scored using the Cholesterol and Saturated Fat Index developed by Connor and colleagues [ 13 ] . Calculations of cholesterol and saturated fat totals were based on weekly rather than daily average food intakes . Data from the food frequency question naires , mailed by patients to the Stanford coordinating center and entered into a microcomputer , were used to generate progress reports that characterized patients ' dietary patterns , prioritized dietary change goals , and provided guides for managing difficult situations by directing patients to relevant sections of a nutrition workbook entitled Good Eating for Good Health developed by the program nutritionist . Patients in the intervention group completed a food frequency question naire during hospitalization that described their eating habits in the previous month . Patients also completed food frequency question naires 6 , 11 , and 26 weeks after admission . Progress reports were mailed to patients within 48 to 72 hours after the food frequency question naires were received . Detailed strategies for maintenance of dietary change were incorporated into the 26-week progress report . Question naires to evaluate outcomes were also completed at 36 and 52 weeks . Lipid-Lowering Drug Therapy The therapeutic goal of a plasma low-density lipoprotein (LDL)-cholesterol value of 2.46 mmol/L ( 95 mg/dL ) adopted for this trial was based on the mean post-treatment level of LDL cholesterol found in patients in the study by Blankenhorn and colleagues [ 4 ] . Patients with mean plasma LDL cholesterol values ( based on measurements in two separate blood sample s drawn 75 and 90 days after infa rct ion ) that exceeded this value were given initial drug therapy according to the four algorithms shown in Table 1 . Patients unable to tolerate bile acid-binding resin or nicotinic acid because of comorbid conditions or potentially adverse interactions with these agents received lovastatin or gemfibrozil . During a visit 90 days after discharge , the nurses did a brief physical examination and obtained a history relevant to hyperlipidemia . They provided detailed counseling to patients regarding the rationale for lipid-lowering drug therapy and ways to maximize drug efficacy and minimize drug side effects , and they advised patients on the schedule of laboratory visits and nurse-initiated follow-up telephone contacts . Table 1 . Initial Drug Therapy * Changes in drug therapy at 120 , 150 , and 180 days , which were coordinated by nurse-initiated telephone contacts , were based on three types of responses to initial therapy : 1 ) if lipoprotein levels returned to normal , the effective drug therapy was continued ; 2 ) if the response was incomplete , the dose of the effective medication was increased or another drug was added , or both ; and 3 ) if comorbid conditions worsened or blood chemistry abnormalities or intolerable side effects occurred , drug dosage was reduced or the patient was switched to another agent or both . A physician lipid specialist and a Stanford-based senior nurse-coordinator provided telephone consultation to the case managers . Before initiating lipid-lowering drug therapy at 90 days and at each subsequent step , nurses review ed the patients ' blood chemistry and lipoprotein values and elicited any symptoms requiring a change in therapy . The Smokers ( N = 756 ) were r and omly assigned by stage of change to ( a ) st and ardized self-help manuals ( ALA+ condition ) , ( b ) individualized manuals matched to stage ( TTT condition ) , ( c ) interactive expert-system computer reports plus individualized manuals ( ITT condition ) , or ( d ) a personalized condition with 4 counselor calls , stage manuals , and computer reports ( PITT condition ) . Over 18 months , the ITT group 's results more than doubled those of the ALA+ group on abstinence measures . The ALA+ and TTT conditions were equivalent over 12 months , but at 18 months the TTT condition was more effective . The ITT condition was the best or comparable with the best treatment at all follow-ups for smokers at all stages of change . Results suggest that an effective expert system has been developed , and discussion focuses on delivering this system to entire population s of smokers This study examines the efficacy of a smoking cessation intervention on abstinence rates and motivation to quit smoking . Participants were adult smokers ( N = 543 ) who presented to the emergency department with chest pain and who were admitted to an observation unit for 24-hour observation to rule out myocardial infa rct ion . Participants were r and omly assigned to either usual care or a tailored intervention employing motivational interviewing and telephone follow-up . All individuals choosing to quit were offered nicotine patch therapy . Follow-up assessment s were conducted at 1 , 3 and 6 months . Abstinence ( 7-day point prevalence ) rates were significantly greater among participants receiving the tailored intervention compared with those given usual care ( OR = 1.62 , 95 % CI [ 1.05 - 2.50 ] ) . The largest difference occurred at 1 month : 16.8 % of usual care and 27.3 % of the tailored intervention group were abstinent , with differences decreasing over time . One-third of participants who were quit at month 6 were late quitters whose initial abstinence began after the 1-month follow up . In addition to treatment assignment , psychosocial variables including motivation to quit , confidence , reduced temptation to smoke in response to negative affect , and the perception that their chest pain was related to their smoking , were significant predictors of cessation . Tailored interventions are effective in promoting initial quit attempts for emergency chest pain patients admitted to an observation unit . Additional intervention may be needed to assist late quitters and to prevent relapse BACKGROUND Time and re source constraints limit the ability of oral health care professionals to help patients quit smoking . Opportunities exist for dental providers to help patients who smoke by enrolling them in tobacco use quitlines . The authors conducted a pilot study to investigate whether such referrals were feasible and effective . METHODS The authors r and omly assigned eight general dental practice s to provide either brief counseling regarding smoking cessation or brief counseling along with referrals to a tobacco use quitline for patients receiving routine dental hygiene care who reported that they were currently smoking cigarettes . RESULTS The authors enrolled 82 patients ( 60 in the tobacco use quitline group , 22 in the brief counseling group ) . At six months , the self-reported , seven-day point prevalence tobacco use abstinence rates were 25.0 percent ( 15 of 60 patients ) in the tobacco use quitline group and 27.3 percent ( six of 22 patients ) in the brief-counseling group ( P approximately 1.0 ) . Twenty-eight ( 47 percent ) of 60 subjects in the tobacco use quitline group completed the initial tobacco use quitline consultation . Abstinence rates among subjects in the quitline group were higher if they completed more telephone consultations . CONCLUSIONS Referral to a tobacco use quitline by dental practice s is a feasible strategy for helping patients quit smoking if efficient links between the dental practice and the tobacco use quitline can be established . Research is needed to evaluate whether it is more effective than st and ard clinical interventions for tobacco use cessation . CLINICAL IMPLICATION S Dental practitioners with limited time and other re sources can assist patients who smoke by referring them to a tobacco use quitline Radon and cigarette smoking have synergistic effects on lung cancer risk . Electric utility company bill stuffers offered free radon test kits to households with at least one smoker . Participating households ( n = 1364 ) were r and omized within a 2 x 2 design to evaluate the main effects of brief telephone counseling and a targeted video on smoking cessation and the establishment of new household smoking bans . Phone counseling was associated with cessation at 3-month follow-up but neither intervention led to 12-month or sustained cessation . While neither intervention had a significant effect on new bans , there were trends in the predicted direction and the combination of the two significantly increased new bans compared with no intervention . The presence of children in the household was associated with new bans . While few households had high levels of radon , such levels were associated with radon mitigation behaviors . Together with a previous study , these results suggest radon risk is a useful and inexpensive way to engage smoking households in risk reduction behaviors , especially the institution of household smoking bans The prevalence of adult tobacco users who utilize the emergency department as patients or parents is disproportionately higher than the national average rates of tobacco use . Thus , it is advised that the emergency department be utilized as a venue for providing tobacco cessation counseling to adult tobacco users . Using a r and omized control trial design , this pilot study evaluated the effect of a brief tobacco cessation intervention for tobacco using parents of children brought to a pediatric emergency department . Participants received either usual care or a brief tobacco cessation intervention based on the first 2 of the 5A 's of the Clinical Practice Guidelines and fax referral to the Quitline . The primary outcome was self-reported repeated point prevalence of tobacco use at 6 weeks and 3 months following the intervention . Secondary aims included number of quit attempts , increases in readiness to quit , comparisons of participants who were successfully retained , and contact rates by Quitline counselors . At 3-month follow-up , compared to the Usual Care Control group , intervention participants were more likely to have made at least one quit attempt ( 59 % vs. 34 % ; p<.01 ) , be seriously thinking about quitting ( 68 % vs. 37 % ; p<.001 ) , and have higher Ladder scores ( 6.2 vs. 5.3 ; p<.05 ) . Study personnel were able to contact 68 % and 52 % , respectively , of participants at 6-week and 3-month follow-up . Quitline counselors were unable to reach 54 % of participants . Our results reveal increased intentions to quit and trends toward quitting , however we experienced difficulties with participant retention . Suggestions for improvements in point prevalence and retention are given Objective : A r and om sample of smokers was offered a transfer to the New York State Smokers ’ Quitline in order to assess smokers ’ acceptance of “ cold calls ” offering quitline services . Method : A 30-minute survey to assess adult tobacco use was administered to 121 western New York smokers who were originally sample d for a r and om digit dialled survey in 2005 , and then re-interviewed one year later , between April and July 2006 . Smokers ’ interest in receiving immediate quitline assistance was assessed at the end of the survey , when the smokers could choose to be transferred to the New York State Smokers ’ Quitline in order to receive the quitline ’s cessation services . Results : 41 % of smokers accepted the offer for , and subsequently received , New York State Smokers ’ Quitline services . After controlling for factors related to cessation , women were more likely to respond to the offer . Conclusions : Although telephone quitline utilisation is low , these data suggest that the dem and is high and “ cold calls ” may be a strategy to extend the use of quitline cessation services STUDY OBJECTIVE To determine the effect of a nurse-managed intervention for smoking cessation in patients who have had a myocardial infa rct ion . DESIGN R and omized , with a 6-month treatment period and a 6-month follow-up . SETTING Kaiser Foundation hospitals in Redwood City , Santa Clara , Hayward , and San Jose , California . PATIENTS Sequential sample of 173 patients , 70 years of age or younger , who were smoking before hospitalization for acute myocardial infa rct ion . Eighty-six patients were r and omly assigned to the intervention and 87 to usual care ; 130 patients ( 75 % ) completed the study and were available for follow-up . INTERVENTION Nurse-managed and focused on preventing relapse to smoking , the intervention was initiated in the hospital and maintained thereafter primarily through telephone contact . Patients were given an 18-page manual that emphasized how to identify and cope with high-risk situations for smoking relapse . MEASUREMENTS AND MAIN RESULTS One year after myocardial infa rct ion , the smoking cessation rate , verified biochemically , was 71 % in the intervention group compared with 45 % in the usual care group , a 26 % difference ( 95 % CI , 9.5 % to 42.6 % ) . Assuming that all surviving patients lost to follow-up were smoking , the 12-month smoking cessation rate was 61 % in the intervention group compared with 32 % in the usual care group , a 29 % difference ( 95 % CI , 14.5 % to 43.5 % ) . Patients who either resumed smoking within 3 weeks after infa rct ion or expressed little intention of stopping in the hospital were unlikely to have stopped by 12 months . CONCLUSIONS A nurse-managed smoking cessation intervention largely conducted by telephone , initiated in the hospital , and focused on relapse prevention can significantly reduce smoking rates at 12 months in patients who have had a myocardial infa rct ion Although a considerable body of evidence supports telephone quit lines for smoking cessation , much less is known about the effectiveness of proactive Telephone Counseling with smokeless tobacco ( ST ) users . We conducted a r and omized controlled trial comparing Telephone Counseling with the distribution of a self-help manual for ST cessation . We recruited 406 adult ST users throughout the state of Minnesota and r and omized them to receive either : ( a ) a self-help manual ( Manual only ) or ( b ) a self-help manual plus proactive telephone-based cessation counseling ( Telephone Counseling ) . The telephone-based treatment included up to four calls in support of quitting , and personalized various cognitive and behavioral strategies that are generally considered effective in tobacco cessation ( such as setting a quit date , examining patterns of use , developing stress reduction skills , avoiding known triggers to use ) . Participants were surveyed by phone at 3 and 6 months to assess both point prevalence and continued abstinence . Prolonged abstinence from all tobacco was 6.8 % and 30.9 % ( p < .001 ) at 3 months and 9.8 % and 30.9 % ( p < .001 ) at 6 months in Manual only and Telephone Counseling , respectively . We found older age , lower dependency , and increased readiness predicted quitting success . Proactive telephone-based counseling is an effective strategy for improving cessation rates among ST users . Future research should determine the components contributing to the intervention success PURPOSE To determine whether an intensive cognitive-behavioral intervention begun during hospitalization when combined with transdermal nicotine replacement therapy is more effective than a minimal counseling intervention combined with transdermal nicotine replacement therapy in helping in patients to quit smoking . METHODS A total of 223 patients who smoked were enrolled in a hospital-based r and omized smoking cessation trial at the San Francisco Veterans Affairs Medical Center . One hundred and seven participants ( 48 % ) received intensive counseling and outpatient telephone follow-up ; 116 participants ( 52 % ) received minimal counseling . All study participants received 2 months of transdermal nicotine replacement therapy . We determined 6-month quit rates by self-report and measured saliva cotinine levels or obtained proxy reports to confirm self-reported smoking cessation at 12 months . Analyses adjusted for baseline differences in the distribution of coronary disease . RESULTS At 6 months , 35 % ( 36/103 ) of the intensive intervention group reported quitting , compared with 21 % ( 23/109 ) of the comparison group ( relative risk [ RR ] = 1.7 ; 95 % confidence interval [ CI ] : 1.1 to 2.7 ) . At 12 months , the self-reported quit rate was 33 % ( 33/99 ) in the intensive intervention group versus 20 % ( 21/103 ) in the comparison group ( RR = 1.7 ; 95 % CI : 1.1 to 2.7 ) . Based on biochemical or proxy confirmation , 29 % ( 30/102 ) in the intensive intervention group versus 20 % ( 21/107 ) in the comparison group quit smoking at 12 months ( RR = 1.6 ; 95 % CI : 0.96 to 2.5 ) . CONCLUSION Hospital-initiated smoking cessation interventions that include transdermal nicotine replacement therapy can improve long-term quit rates Current treatment guidelines recommend that all smokers be given motivational or action-oriented counseling , as is appropriate to their readiness to quit smoking . The present study assessed the acceptability and impact of a proactively delivered , motivationally tailored phone counseling program targeted to women with elevated risk for cervical cancer . Female smokers with a recent abnormal pap exam or a colposcopy were contacted and invited to participate , regardless of their interest in quitting smoking . Participants were r and omly assigned to usual care ( UC ) or UC plus motivationally enhanced phone counseling ( MEC ) . The intervention was well received : 79 % of eligible women enrolled ( n = 275 ) , and 90 % completed at least three of four calls . Participation did not vary by baseline motivation to quit . Compared with control subjects , counseling participants were more likely to seek additional treatment services and had a higher 7-day point-prevalence abstinence rate at 6 months ( 20 % MEC vs. 12 % UC , p<.05 ) . MEC impact was sustained at 12 months , but abstinence increased among the UC group ( 18 % MEC vs. 20 % UC , p = ns ) . There was no difference in repeated point-prevalence abstinence at 6 and 12 months ( 11 % MEC vs. 10 % UC , p = ns ) . Outcomes were similar in a subgroup of 229 women who , at baseline , were interested in quitting in the next 6 months We tested an intervention to help smokers abstain ( fast ) from smoking before surgery , maintain abstinence postoperatively , and achieve long-term cessation . A r and omized experiment included 237 patients admitted for presurgical assessment who smoked . The intervention included counseling and nicotine replacement therapy . Treatment group participants ( 73.0 % ) were more likely to fast than were controls ( 53.0 % ) : chi(2)(1 , N = 228 ) = 8.89 , p = .003 , and more likely to be abstinent 6 months after surgery ( 31.2 % vs. 20.2 % ) . There was no significant difference in the abstinence rates at 12 months after surgery , chi(2)(1 , N = 169 ) < .001 , p = 1.00 . Encouraging patients to fast from smoking before surgery and postoperative support are efficacious ways to reduce preoperative and immediate post-operative tobacco use Health care increasingly incorporates telephone counseling , but the interactions supporting its delivery are not well understood . The authors ’ clinical trial of a tailored , nurse-administered smoking cessation intervention for surgical patients included a telephone counseling component and provided an opportunity to describe the interaction dynamics of proactive telephone counseling over the course of 4 months . Tape-recorded telephone counseling calls for 56 consecutively enrolled individuals r and omized to the intervention group result ed in a data set of 368 calls , which were transcribed and analyzed using constant comparative methods . The findings revealed varying interaction dynamics depending on the nurse ’s level of engagement with participants and participants ’ motivation to stop smoking . The authors identified four interaction dynamics : affirming/working , chasing/skirting , controlling/withdrawing , and avoiding commitment . Shifts in interaction dynamics were common and influenced the provision of support both positively and negatively . The findings challenge many assumptions underlying telephone counseling and suggest strategies to improve its delivery PURPOSE To conduct an exploratory study of two interventions to help smokers abstain over a period of 3 months . The specific aims were to describe the outcomes , test feasibility of the study design , and evaluate effect size . DESIGN AND METHODS A r and omized experimental design was used in a sample of 42 patients who received multicomponent treatment intervention ( MTI ) or st and ard care ( SC ) in a midwestern city in the United States . Variables were behavioral ( quit rate , self-efficacy , motivation ) , psychosocial ( depression , partner interaction ) , and symptom management ( use of nicotine replacement therapy [ NRT ] ) . Data analysis included descriptive statistics and repeated measures ANOVA . RESULTS The typical participant was Caucasian , middle aged , nicotine dependent , married or partnered , and employed , and had a high school education . Participants in the MTI group were more likely to use NRT and to have higher self-reported quit rates at follow-up . Statistically significant differences were found between groups over time for self-efficacy and positive to negative behavior ratio . Barriers to quitting were relapse , stress , weight gain , lack of support , and depression that were more frequent in the SC group . For effect size ( 0.25 ) , probability level ( .05 ) , and power ( .80 ) , a sample size of 140 patients was calculated . CONCLUSIONS The MTI group had higher quit rates , more NRT , higher self-efficacy , and more positive behavioral interactions . Limitations of the study included self-report of tobacco use , small sample , and attrition . The investigators suggest a future study with a larger sample to test whether multicomponent interventions with telephone calls after discharge are more effective than is st and ard care in helping patients to quit and continue to abstain from smoking Objective : This study evaluates alternative protocol s in telephone counselling for smoking cessation . Design : The American Cancer Society enrolled 6322 clients in a r and omised trial comparing three counselling formats of varying duration and frequency of contact , with or without booster sessions , and mailed self help booklets without telephone counselling . Setting and participants : Participants were drawn from callers to the American Cancer Society ’s National Cancer Information Center seeking assistance with smoking cessation who provided informed consent and were adult daily smokers , ready to make a quit attempt within two weeks , and from states not served by an evidence based proactive telephone counselling programme . Outcomes : Six-month cessation rates ( 30-day point prevalence ) were measured in telephone interviews . Results : There was a significant counselling effect . The overall cessation rates that were yielded by a brief protocol including booster sessions were equivalent to those obtained with the American Cancer Society ’s st and ard protocol with boosters . Conclusions : Based on these findings , the abbreviated protocol with five sessions and two boosters is considered to be an option for improving cost efficiency in the delivery of this service A r and omised trial evaluated the American Cancer Society ’s telephone counselling service to assist smoking cessation . Counselling nearly doubles a smokers ’ odds of quitting and maintaining cessation for one year . The estimated cost for each case of maintained smoking cessation attributable to counselling availability is approximately $ 1300 We tested whether a 3-month beneficial effect of telephone counseling as an adjunct to the use of medications for smoking cessation was maintained through 12 months . Health plan members filling a prescription for cessation medications were r and omized either to a no-contact control group or to proactive recruitment into telephone counseling . An increased point-prevalence quit rate at 3 months ( 33.1 % vs. 27.4 % , p<.05 ) among smokers r and omized to proactive recruitment for telephone counseling was not maintained . Although at 12 months smokers in the proactive recruitment arm were more likely to report a 24-hr quit attempt , compared with control group smokers ( 86.7 % vs. 80.8 % , p = .027 ) , we found no differences between the groups in repeated ( 3-month and 12-month ) 7-day point-prevalence quit rates . In an analysis of predictors of quitting , age , marital status , making a lifestyle change , and the presence of household smokers were associated with repeated 3-month and 12-month point-prevalence abstinence . Offering telephone counseling to insured smokers who have filled prescriptions for cessation medications did not increase long-term quit rates . Although other variations of this approach might be tested , we suspect that it might be more useful to test innovative ways to influence the factors we identified as being most strongly predictive of lack of successful quitting AIM To assess the effectiveness of a new computer-generated tailored advice programme design ed to be used by smokers and recent quitters having problems staying stopped . DESIGN R and omized trial comparing a series of question naire assessment s leading to tailored computer-generated advice letters mailed at strategically relevant times , to a no extra treatment control sent st and ardized printed self-help material s. SETTING Victoria , Australia . PARTICIPANTS A total of 1058 smokers or recent quitters recruited from callers to the Quitline . MEASUREMENTS Smoking status and sustained abstinence at 12-month follow-up , plus extent of participation in the intervention . FINDINGS Using a conservative analysis ( missing data coded as a treatment failure ) , 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice ( 20 % ) than the st and ard printed material s condition ( 12 % ) at 12-month follow-up OR 1.82 ( 1.31 - 2.55 ) ) . Group differences in point prevalence abstinence ( 28 % intervention , 25 % control ) were not significant . Among participants in the tailored advice condition , 6-month sustained abstinence was associated with the number of advice letters received . CONCLUSION The provision of a series of tailored , computer-generated advice letters result ed in greater rates of sustained cessation than for controls . A dose-response relationship was found , with increased compliance with the intervention associated with improved cessation outcomes . The programme appears to have much of its effect by preventing relapse Brief supportive telephone counseling is a promising adjunct to self-help smoking cessation programs . This article reports rates of participation , predictors of participation , and content of telephone counseling calls with nonvolunteer smokers who were identified through health surveys administered to a r and om sample of enrollees in a health maintenance organization . Eighty-six percent of smokers accepted at least one of three counselor calls ; 66 % accepted all three calls . Baseline characteristics associated with acceptance of calls included being female and greater average length of time to the first cigarette of the day . Acceptance did not differ significantly by stage of cessation . First calls with smokers who accepted all three calls were longer and were more likely to be with smokers who were willing to take a specific next action step . Overall , 12 % of the sample reported having quit smoking by the third counseling call , with the highest quit rate ( 23 % ) among smokers who , at baseline , were planning to quit in the next month . Implication s for large-scale interventions with smokers in health care and other organizations are discussed OBJECTIVE To describe the design , implementation , baseline data , and feasibility of establishing a disease management program for smoking cessation in rural primary care . METHOD The study is a r and omized clinical trial evaluating a disease management program for smoking cessation . The intervention combined pharmacotherapy , telephone counseling , and physician feedback , and repeated intervention over two years . The program began in 2004 and was implemented in 50 primary care clinics across the State of Kansas . RESULTS Of eligible patients , 73 % were interested in study participation . 750 enrolled participants were predominantly Caucasian , female , employed , and averaged 47.2 years of age ( SD=13.1 ) . In addition to smoking , 427 ( 57 % ) had at least one additional major risk factor for cardiovascular disease ( diabetes , hypertension , high cholesterol , heart disease or stroke ) . Participants smoked on average 23.7 ( SD=10.4 ) cigarettes per day , were contemplating ( 61 % ) or preparing to quit ( 30 % ) , were highly motivated and confident of their ability to quit smoking , and reported seeing their physicians multiple times in the past twelve months ( Median=3.50 ; Mean=5.48 ; SD=6.58 ) . CONCLUSION Initial findings demonstrate the willingness of patients to enroll in a two-year disease management program to address nicotine dependence , even among patients not ready to make a quit attempt . These findings support the feasibility of identifying and enrolling rural smokers within the primary care setting Patterns of smoking cessation using 6- and 12-month follow-up data are reported for 1,261 primary care patients r and omized to 3 physician-delivered smoking interventions : advice only ( AO ) , counseling ( CI ) , and counseling plus availability of nicotine-containing gum ( CI + NCG ) . One-week-point-prevalence cessation rates at 12 months did not differ among the interventions : AO ( 15.2 % ) , CI ( 12.9 % ) and CI + NCG ( 16.7 % ) . However , maintained cessation rates ( abstinent at both 6 and 12 months ) increased with intervention intensity : AO ( 6.0 % ) , CI ( 7.8 % ) and CI + NCG ( 10.0 % ) : Test of trend chi 2 = 5.06 , p = .02 . CI + NCG was significantly higher than AO ( p = .02 ) . The findings support the following conclusions : Brief physician-delivered intervention with availability of nicotine-containing gum can have a beneficial long-term effect on smoking cessation , and cohort data as well as point-prevalence rates are important when assessing the long-term impact of lifestyle interventions OBJECTIVE . Provision of telephone smoking cessation counseling can increase the rate of quitting smoking . The US Public Health Service recently helped to establish a free national quitline enrollment service . No previous surveys have assessed the acceptability to parents of enrollment in quitline counseling in the context of their child 's health care visits . Therefore , the objective of this study was to assess acceptability to parents of enrollment in quitline counseling and to compare that with the reported rate of actually being enrolled in any smoking cessation counseling outside the office in the context of the child 's health care visit . METHODS . Data were collected by a national r and om-digit-dial telephone survey of households from September to November 2004 . The sample is weighted by race and gender on the basis of the current US Census to be representative of the US population . RESULTS . Of 3615 eligible respondents contacted , 3011 ( 83.3 % ) completed surveys ; 958 ( 31.8 % ) who completed the survey were parents with children under the age of 18 years . Of these parents , 187 ( 19.7 % ) were self-identified smokers . Of the parents who smoked , 113 ( 64.2 % ) said that they would accept enrollment in a telephone cessation program if the child 's doctor offered it to them . In contrast , of the 122 smoking parents who accompanied their child to the doctor in the past year , only 11 ( 9 % ) had any counseling recommended to them , and only 1 ( 0.8 % ) was actually enrolled . These results did not vary by parent age , gender , race , or child age . CONCLUSIONS . When interacting with parents who smoke , child health care providers have low rates of referring and enrolling parents in any services related to smoking . Enrollment in quitlines would be acceptable to the majority of parents in the context of their child 's health care visit . Tobacco control efforts in the child health care setting should include implementation of office systems that can facilitate enrollment of parental smokers in telephone quitlines OBJECTIVES Transdermal nicotine patches have shown considerable promise in improving smoking cessation outcomes . The present study assessed telephone support as an adjunct to a managed care-based , single-session group orientation smoking cessation program with nicotine patch therapy . METHODS The unit of r and omization was the orientation session ( n = 35 ) . Subjects ( n = 509 ) were r and omly assigned to a group session without telephone support , the session plus access to a toll-free help line , or the session with telephone help line plus active telephone outreach . RESULTS Contrary to hypothesis , there were no differences between treatment conditions . Overall abstinence rates were 22 % at 6 months and 21 % at 1 year . Fewer than 1 % of eligible subjects called the toll-free help line . An average of 3.8 of a possible 4 calls were completed in the telephone outreach condition . CONCLUSIONS Abstinence results obtained in this program were comparable to those obtained with more extensive counseling . However , there was no evidence of benefit from telephone support beyond the initial physician-led group orientation session This study evaluated the effect of telephone counseling as an adjunct to a self-help program for smoking cessation conducted through the mail . We obtained demographic and consumption information on those smokers who requested participation in the study . These participants ( N = 200 ) were r and omized into two study groups : ( 1 ) the st and ard self-help group ( n = 100 ) ( median age : 35.1 years ; pretreatment consumption of 28.0 cigarettes/day ) ; ( 2 ) the self-help group receiving additional multiple-contact telephone counseling ( n = 100 ) ( median age : 36.7 years ; pretreatment consumption of 27.3 cigarettes/day ) . At the 12-month follow-up , the carbon monoxide in expired air was used to distinguish nonsmokers from smokers . Significant differences were found in the rates of continuous abstinence in both groups for each period evaluated . In the st and ard self-help group , the continuous abstinence rate at the 3-month follow-up was 21 % , 18 % at the 6-month follow-up , and 14 % at the 12-month follow-up . The telephone counseling group yielded a 48 % continuous abstinence rate at the 3-month follow-up , 40 % at the 6-month follow-up , and 27 % at the 12-month follow-up . The results of this r and omized controlled trial show that telephone counseling was an effective aid for the smoking cessation program OBJECTIVE To evaluate telephone counseling for moist snuff use . METHODS We recruited 221 adult males using snuff and r and omized them into a telephone-counseling intervention or a quit-manual comparison group . Subjects were contacted by mail at 3 and 6 months to complete a 4-page follow-up question naire . RESULTS A significantly higher proportion of subjects r and omized to the intervention quit tobacco at each time point compared to the comparison group . CONCLUSIONS With appropriate staff training , moist snuff and other types of nonsmoked tobacco should be added to the state-funded smoking cessation quit lines started in recent years OBJECTIVES This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs . METHODS Twenty-four worksites were r and omized to 6 conditions that differed in cessation program format and the use of incentives . Programs were offered for 18 months in each worksite . A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation . RESULTS A total of 407 ( 16.9 % ) of the smoker cohort registered for programs ; on the 12- and 24-month surveys , 15.4 % and 19.4 % of the cohort , respectively , reported that they had not smoked in the previous 7 days . Registration for programs in incentive sites was almost double that of no-incentive sites ( 22.4 % vs 11.9 % ) , but increased registration did not translate into significantly greater cessation rates . Program type did not affect registration or cessation rates . CONCLUSIONS Although incentives increase rates of registration in worksite smoking cessation programs , they do not appear to increase cessation rates . Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites OBJECTIVES To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release ( SR ) in combination with behavioral interventions of minimal intensity ( tailored mailings [ TM ] ) or moderate intensity ( proactive telephone calls [ PTC ] ) for smoking cessation in an actual practice setting . STUDY DESIGN Open-label , r and omized trial , with 1-year follow-up , conducted in a large health system based in Seattle , Washington . METHODS A total of 1524 adult smokers interested in quitting smoking were r and omly assigned to receive 150 mg bupropion SR daily and PTC ( n = 382 ) , 150 mg bupropion SR daily and TM ( n = 381 ) , 300 mg bupropion SR daily and PTC ( n = 383 ) , or 300 mg bupropion SR daily and TM ( n = 378 ) . Sufficient medication for 8 weeks of dosing was provided to patients . The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date . RESULTS Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM , the additional cost result ed in lower cost effectiveness . The PTC behavioral intervention was more expensive than TM , but the additional effectiveness result ed in almost equivalent cost effectiveness at the 150-mg dose . Costs per additional 12-month nonsmoker ( above that expected for placebo ) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars ; for the 300-mg groups these costs were 1342 dollars and 2129 dollars , respectively . Cost per life-year and quality -adjusted life-years ( QALYs ) saved varied substantially by age and treatment , but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population . CONCLUSIONS Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments , within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective AIMS To examine heterogeneity in outcome following treatment for smoking cessation with combined bupropion SR and behavioral counseling in women and men . DESIGN , SETTING , PARTICIPANTS This study included 875 women and 649 men recruited from a large health-care system and r and omized to one of four combinations of treatment [ two dosage levels of bupropion SR ( Zyban , 150 mg and 300 mg ) were crossed with two counseling programs of lower and higher intensity to create a four-cell design ] . MEASUREMENTS AND FINDINGS A comprehensive set of relevant individual characteristics prior to treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified six subgroups in women that ranged in proportion of non-smokers from 9.8 % to 42.9 % and six subgroups in men that ranged in proportion of non-smokers from 17.3 % to 50.0 % . CONCLUSIONS These results indicate the presence of a substantial amount of variation in treatment outcome among women and men receiving combined bupropion SR and counseling . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following cessation Smoking markedly increases the risk of asbestos-related lung cancer . We conducted a r and omized pilot trial of a telephone-based smoking cessation intervention in asbestos workers . Fifty-nine smokers were assigned to either a control or telephone-based smoking cessation treatment group and were followed-up at 6 months . Intent-to-treat analysis revealed a 16.7 % quit rate at 6 months for the intervention group compared to 6.9 % for the control group ( P = 0.25 ) . Treatment-received quit-rates were 33 % for the intervention group and 6.9 % for the control group ( P = 0.05 ) . The intervention group was twice as likely to use smoking cessation medicines and progressed further along the stage of change continuum compared with the control group . Incorporating telephone-based smoking cessation treatment into medical screening activities for asbestos workers is feasible and the intervention is effective in increasing quit rates at 6 months OBJECTIVE A pilot study was conducted to determine the feasibility and potential efficacy of an interactive voice response ( IVR ) follow-up system for smokers recently hospitalized with coronary heart disease ( CHD ) . METHODS Ninety-nine smokers hospitalized with CHD completed a baseline question naire , were provided with bedside counseling , and offered nicotine replacement therapy . They were r and omly assigned to a usual care ( UC ) or an IVR group . The IVR group received automated telephone follow-up calls 3 , 14 and 30 days after discharge inquiring about their smoking status and confidence in remaining smoke-free . When deemed necessary , they were offered additional counseling . Smoking status was determined 52 weeks after hospital discharge . RESULTS The 52-week point prevalence abstinence rate in the IVR group was 46.0 % compared to 34.7 % in the UC group ( OR=1.60 , 95 % CI : 0.71 - 3.60 ; P=.25 ) . After adjustment for education , age , reason for hospitalization , length of hospitalization , and quit attempts in the past year , the odds of quitting in the IVR group compared to the UC group were 2.34 ( 95 % CI : 0.92 - 5.92 ; P=.07 ) . CONCLUSIONS IVR is a promising technology for following CHD patients attempting to quit smoking following discharge from hospital , however , a larger trial is required to confirm its efficacy . PRACTICE IMPLICATION S IVR may enhance the timely provision of follow-up counseling for smoking cessation in patients with CHD To date , only one study has been published on individual characteristics associated with outcome following st and ard treatment with bupropion SR for smoking cessation . To investigate treatment outcome beyond the 6-week end-of-treatment point , the present study examined characteristics associated with more clinical ly relevant smoking endpoints following treatment with bupropion SR in a large health care system . A total of 1,524 smokers ( 649 men and 875 women ) of average age 45.1 years were r and omized to receive one of four combinations of bupropion SR ( 150 or 300 mg ) and behavioral counseling ( tailored mailings or proactive telephone counseling ) and assessed for point-prevalent smoking status at 3 and 12 months . Multiple logistic regression analyses of potential risk factors for 12-month point-prevalent smoking and for persistent smoking ( point-prevalent smoking at both follow-ups ) following treatment were conducted for men and women combined and separately . Risk factors for smoking at both endpoints in the combined sample included treatment with tailored mailings , female gender , younger age , higher levels of tobacco dependence , shorter previous quit attempts , previous use of nicotine replacement therapy , and report of current depressive symptoms or lifetime depression . Risk factors for smoking following treatment identified in women only included treatment with the lower dose of bupropion SR , younger age , and higher perceived stress , whereas those that were unique to men included the presence of lifetime depression . The results are discussed in terms of their implication s for the need for more effective treatments in general , and the role of individual differences in the likelihood of returning to smoking following treatment for quitting BACKGROUND The authors evaluated the incremental efficacy of telephone counselling by a nurse in addition to physician advice and nicotine replacement therapy in helping patients to stop smoking . METHODS The trial was conducted at the University of Ottawa Heart Institute . A total of 396 volunteers who smoked 15 or more cigarettes daily were r and omly assigned to either of 2 groups : usual care ( control group ) and usual care plus telephone counselling ( intervention group ) ; the groups were stratified by sex and degree of nicotine dependence . Usual care involved the receipt of physician advice on 3 occasions , self-help material s and 12 weeks of nicotine replacement therapy . Telephone counselling was provided by a nurse at 2 , 6 and 13 weeks after the target quit date . Point-prevalent quit rates were determined at 52 weeks after the target quit date . RESULTS The point-prevalent quit rates at 52 weeks did not differ significantly between the control and intervention groups ( 24.1 % v. 23.4 % respectively ) . The quit rates did not differ significantly at the secondary measurement points of 4 , 12 and 26 weeks . INTERPRETATION Brief physician assistance , along with nicotine replacement therapy , can help well-motivated smokers to quit . Three additional sessions of telephone counselling by a nurse were ineffective in increasing quit rates . This form of assistance may be useful in the absence of physician advice or when self-selected by patients Objectives : Since June 1997 , Australia has run its first nationally coordinated mass media anti-smoking campaign , with all States collaborating to offer a st and ard Quitline service . An overview of the Australian national Quitline service is presented as well as two studies describing ( a ) the relationship between television advertising and call volume and type , and ( b ) the quit rates of callers over time . Design : Data on extent of advertising , as measured by weekly television target audience rating points ( TARPs ) , is compared with weekly call volume and disposition . A r and omly selected sample of callers was followed up at 3 weeks , 6 months and 12 months to assess caller appraisal and quit rates . Setting : The Australian Quitline service , in the context of a nationally coordinated , major anti tobacco campaign . Results : In a one year period from June 1997 , 3.6 % of adult Australian smokers called the Quitline . Weekly call volume was strongly related to TARPs and increased further when an advertisement specifically promoting the Quitline was broadcast . Calls involving requests for counselling , as opposed to brief calls to request quit material s , were more likely with lower TARPs . Of the cohort who were smoking at baseline , 28 % reported they had quit smoking at a one year follow up and 5 % had been quit for an entire year . Conclusions : In the context of a national mass media campaign , this study illustrates that it is possible to bring together differing State based services to provide an accessible , acceptable , and effective quit smoking service Abstract Aim : To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release ( SR ) 150 or 300 mg/day combined with behavioural counselling . Design , setting , participants : Smokers were recruited from a large healthcare system and then r and omized to receive either bupropion SR 150 mg/day ( n = 763 ) or 300 mg/day ( n = 761 ) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach . Measurements and findings : A comprehensive set of relevant individual pre-treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months . Seven subgroups were identified among those receiving bupropion SR 150 mg/day ( proportion of nonsmokers at 12 months ranged from 13.7 % to 43.5 % ) and eight subgroups among those receiving bupropion SR 300 mg/day ( proportion of nonsmokers at 12 months ranged from 9.6 % to 51.7 % ) . In the 150-mg/day group , those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer . In the 300 mg/day group , those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level . Across all subgroups , cost per 12-month quitter ranged from a low of $ US302 to a high of $ US2502 . Conclusions : These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR , with substantial cost consequences . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt This study compared 2 minimal interventions for reducing relapse in ex-smokers . One intervention involved 12-month access to a telephone hot line . In the other intervention , 8 relapse-prevention booklets were mailed to participants over 1 year . The 2 interventions were crossed in a 2 x 2 factorial design , yielding control , hot-line-only , mailings-only , and combined conditions . The criterion of at least 1 week of abstinence at baseline was met by 584 participants , 446 of whom also completed a 12-month assessment . Repeated mailings , but not the hot line , reduced relapse for those participants who had been abstinent for less than 3 months at baseline . At follow-up , 12 % of those in the mailings conditions were smoking again compared with 35 % in the nonmailing conditions . As predicted , both interventions were effective at attenuating the association between depressive symptoms and poor outcome found in the control condition Telephone counseling is a popular modality for smoking cessation treatment ; however , little attention has been paid to evaluating the efficacy of different contents of calls . This study compared 2 types of proactive telephone calls following a group program . Participants were r and omized to receive either : ( a ) basic content , consisting primarily of support ; or ( b ) enhanced content , tailored to the stage of cessation ( still smoking , abstinent , or relapsed ) and targeting factors hypothesized to be related to success ( motivation , self-efficacy , and negative mood ) . There was a significant interaction between treatment condition and gender . For men , the enhanced condition produced better abstinence rates through 15 months and lower relapse rates . For women , the basic condition was better . History of depression did not interact with condition Personality traits and risk perceptions were examined as predictors of changes in smoking behavior . Participants ( N = 697 ) were part of a r and omized controlled trial of interventions to reduce exposure to the combined hazard of radon and cigarette smoke . Participants with higher perceived risk at baseline for the combination of smoking and radon were more likely to have a more restrictive household smoking ban in place at 12-month follow-up ( p < .05 ) . Risk perceptions also predicted reductions in the total number of cigarettes smoked in the home for participants in the video intervention who had high or moderate levels of extraversion ( p < .01 ) . Greater perceived risk predicted whether highly or moderately conscientious women quit smoking ( p < .05 ) . The moderating effects of personality traits should be considered when evaluating risk-reduction interventions OBJECTIVE This study was undertaken to evaluate a smoking cessation intervention provided to women smokers as follow-up to cervical cancer screening . METHODS Women who had had a Pap test in the prior month ( N = 4,053 ) were called to complete a survey that assessed smoking status ; 580 identified smokers were r and omized to receive Usual care ( n = 292 ) or a Self-help intervention ( n = 288 ) that included a self-help booklet , a smoking and reproductive health information card , and three telephone counseling calls . Women were followed up at 6 and 15 months post-base line . RESULTS Cessation rates in the Usual care ( UC ) and Self-help ( SH ) groups did not differ at the 6-month ( UC 10.5 % vs SH 10.9 % , P = 0.56 ) or 15-month follow-up ( UC 15.5 % vs SH 10.6 % , P = 0.17 ) . Among women with an abnormal Pap test result there were no differences by study group in cessation rates at 6-month ( UC 9.8 % vs SH 11.0 % , P = 0.71 ) or 15-month follow-up ( UC 14.6 % vs SH 13.4 % , P = 0.96 ) . CONCLUSION Integrating interventions into the clinical setting and involving providers at the point of care may have greater potential for capitalizing on this " teachable moment . OBJECTIVES To examine the options for use , efficiency , and effectiveness for structuring a population -based telephone smoking-cessation service . METHODS Callers ( n=632 ) to a 1 - 800 number were r and omized in a 2 ( 50-minute counseling with 2/6 calls ) x 2 ( pamphlet/booklet ) design with print only control . RESULTS Six-month use of the service was 0.6 % of adult smokers . Service promotion cost 31.02 dollars/person . Telephone counseling result ed in higher continued abstinence ( 5 % ) than did print only ( 1 % ) , P<.05 . Amount of print and calls did not increase cessation . Six calls result ed in lower completion rates than 2 ( 22 % vs 56 % , P<.05 ) . CONCLUSIONS For planning , consider 1 % use , low-cost promotion , pamphlet , 50-minute initial counseling plus 2 follow-ups , and minimize call-attempts BACKGROUND Lack of interest has been cited as a reason not to offer cessation assistance to smokers , but research suggests that smokers accept treatments offered proactively . This study assessed acceptability , utilization , and effectiveness of free smoking cessation treatment among diverse primary care patients . METHOD Medical assistants invited 4174 adult smokers to participate . Enrollees ( 1869 ) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R ) program , and for some , individual counseling . RESULTS In nearly 68 % of cases , patients accepted a treatment invitation ; 77 % of eligible smokers enrolled ; 85 % of these picked up free patches . Given a choice of treatments , 75 % of participants elected a psychosocial treatment in addition to patch therapy . Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year , with no significant treatment effects . Minority patients showed greater initial interest but less utilization did than White patients . CONCLUSIONS Free , readily accessible smoking cessation treatment offered in primary care setting s was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins . Psychosocial treatment components did not significantly increase abstinence rates . Barriers , rather than lack of interest , may keep minority smokers from using cessation treatments Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews BACKGROUND Cigarette smoking is the greatest cause of preventable mortality in the United States . Because most smokers would like to quit and most hospitals are smoke free , surgical admissions represent a window of opportunity for tobacco cessation interventions . METHODS A total of 324 patients ( 98 % men ) , aged 25 to 82 years , who were current smokers and who underwent noncardiac surgery were enrolled in a r and omized controlled trial at the Veterans Affairs Medical Center , San Francisco , Calif. One hundred sixty-eight participants ( 52 % ) received a multicomponent intervention design ed to increase self-efficacy and coping skills that included face-to-face in-hospital counseling , viewing a smoking cessation videotape , self-help literature , nicotine replacement therapy , and 3 months of telephone follow-up . One hundred fifty-six participants ( 48 % ) received self-help literature and brief counseling lasting 10 minutes . Serum or saliva cotinine levels were measured to confirm self-reported smoking cessation . RESULTS At 12 months of follow-up , the self-reported quit rate was 27 % among the intervention group and 13 % among the comparison group ( relative risk , 2.1 ; 95 % confidence interval , 1.2 - 3.5 ; P < .01 ) . Based on biochemical confirmation , 15 % of the intervention group , compared with 8 % of the comparison group , quit smoking at 12 months ( relative risk , 2.0 ; 95 % confidence interval , 1.0 - 3.9 ; P = .04 ) . CONCLUSIONS A smoking cessation intervention targeted at smokers hospitalized for noncardiac surgery can increase long-term quit rates . Surgical hospitalizations provide an opportunity to reach smokers who want to quit smoking PURPOSE We undertook a study to assess the impact of comparative feedback vs general reminders on practice -based referrals to a tobacco cessation quit line and estimated costs for projected quit responses . METHODS We conducted a group-r and omized clinical trial comparing the impact of 6 quarterly ( 18 months ) feedback reports ( intervention ) with that of general reminders ( control ) on practice -based clinician referrals to a quit-line service . Feedback reports were based on an Achievable Benchmark of Care approach using baseline practice , clinician , and patient survey responses , and referrals per quarter . Comparable quit responses and costs were estimated . RESULTS Three hundred eight clinicians participated ( 171 family medicine , 88 internal medicine , 49 obstetrics-gynecology ) from 87 primary care practice s in Michigan . After 18 months , there were more referrals from the intervention than from the control practice s ( 484 vs 220 ; P < .001 ) . Practice facsimile ( fax ) referrals ( 84 % , n = 595 ) exceeded telephone referrals ( 16 % , n = 109 ) , but telephone referrals result ed in greater likelihood of enrollment ( 77 % telephone vs 44 % fax , P < .001 ) . The estimated number of smokers who quit based on the level of services utilized by referred smokers was 66 in the feedback and 36 in the gentle reminder practice s. CONCLUSION Providing comparative feedback on clinician referrals to a quit-line service had a modest impact with limited increased costs BACKGROUND State-level tobacco quitlines are integrating nicotine replacement therapy ( NRT ) into service . Because of funding limitations some provide short courses of NRT . No r and omized trial has evaluated the relative benefit of short versus st and ard treatment . DESIGN A two-cell r and omized trial comparing 2 weeks of NRT to 8 weeks . SETTING / PARTICIPANTS Uninsured callers to the Oregon Quit Line during a free-patch initiative from October 18 , 2004 , to May 5 , 2005 , who were 18 years or older , smoked five or more cigarettes per day , did not have a medical contraindication to NRT use , and were interested in quitting in 30 days . Data were collected from April to November 2005 , and analyzed in 2006 - -2007 . INTERVENTION Participants were eligible for two phone counseling sessions . 1154 participants were r and omized to receive via the mail either 2 or 8 weeks of nicotine patches . MEASURES Primary outcome was self-reported complete abstinence from tobacco for 30 or more days at the 6-month phone survey . Secondary outcomes were 7-day point prevalence and 90-day abstinence , satisfaction , and patch use . ORs and CIs were computed . Cost per quit and incremental cost per additional quit were computed based on program costs . RESULTS Intent-to-treat 30-day abstinence was 14.3 % in the 2-week group , and 19.6 % in the 8-week group ( OR 1.45 [ CI=1.01 , 2.12 ] ) . Average cost per quit was $ 1156 for 2 weeks and $ 1405 for 8 weeks , with an incremental cost effectiveness of $ 2068 . Satisfaction increased from 90 % to 97 % with 8 weeks . Those receiving 8 weeks of NRT took more calls ( 2.0 vs 1.6 ) and used more patches ( 6.3 weeks vs 4.3 weeks ) , but were less likely to purchase patches ( 16.2 % vs 39.3 % ) . CONCLUSIONS Eight weeks of patches improved quit rates compared with 2 weeks , and was cost effective OBJECTIVES This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy . METHODS Pregnant smokers at 2 managed care organizations were r and omized to receive a self-help booklet only , prepartum relapse prevention , or prepartum and postpartum relapse prevention . Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks , 6 months , and 12 months postpartum . RESULTS The pre/post intervention delayed but did not prevent postpartum relapse to smoking . Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks ( booklet group , 30 % ; prepartum group , 35 % ; pre/post group , 39 % ; P = .02 [ different superscripts denote differences at P < .05 ] ) and at 6 months ( booklet group , 26 % , prepartum group , 24 % ; pre/post group , 33 % ; P = .04 ) postpartum . A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence . There was no difference between the groups in prevalent abstinence at 12 months postpartum . CONCLUSIONS Relapse prevention interventions may need to be increased in duration and potency to prevent post-partum relapse OBJECTIVE To examine whether reimbursement for Provider Counseling , Pharmacotherapies , and a telephone Quitline increase smoking cessation relative to Usual Care . STUDY DESIGN R and omized comparison trial testing the effectiveness of four smoking cessation benefits . SETTING Seven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate . PARTICIPANTS There were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months . INTERVENTION(S ) ( 1 ) Usual Care , ( 2 ) reimbursement for Provider Counseling , ( 3 ) reimbursement for Provider Counseling with Pharmacotherapy , and ( 4 ) telephone counseling Quitline with nicotine patch . MAIN OUTCOME MEASURE Seven-day self-reported cessation at 6- and 12-month follow-ups . PRINCIPAL FINDINGS Unadjusted quit rates assuming missing data = smoking were 10.2 percent ( 9.0 - 11.5 ) , 14.1 percent ( 11.7 - 16.5 ) , 15.8 percent ( 14.4 - 17.2 ) , and 19.3 percent ( 17.4 - 21.2 ) at 12 months for the Usual Care , Provider Counseling , Provider Counseling + Pharmacotherapy , and Quitline arms , respectively . Results were robust to sociodemographics , smoking history , motivation , health status , and survey nonresponse . The additional cost per quitter ( relative to Usual Care ) ranged from several hundred dollars to $ 6,450 . CONCLUSIONS A telephone Quitline in conjunction with low-cost Pharmacotherapy was the most effective means of reducing smoking in the elderly |
11,276 | 31,275,643 | Although none of the studies reported a thromboembolic event after interruption of anticoagulation , the follow-up periods were short and inconsistent , and the heightened thromboembolic risk when stopping anticoagulation is well known in the literature .
Heparin bridging was associated with an increased bleeding incidence . | Currently , the number of patients on oral anticoagulation is increasing .
There is a paucity of data regarding maintaining oral anticoagulation ( especially novel oral anticoagulants ) around the time of specific dental procedures .
A dentist has three options : either to stop anticoagulation , to continue it , or to bridge with heparin . | This prospect i ve r and omized study analyses the use of a prescribed 4.8 % tranexamic acid post-operative mouthwash over 2 days vs 5 days to prevent bleeding in patients taking warfarin who require dental extraction s. Eighty-five patients therapeutically anticoagulated with warfarin for various conditions , ranging in age from 21 to 86 years and requiring dental extraction s , were r and omly divided into two groups . Group A postoperatively received a 4.8 % tranexamic acid mouthwash to be used over a 2-day period . Group B received the same mouthwash and instructions postoperatively , to be taken over 5 days . All procedures were performed on an ambulatory basis under local anaesthetic by the same surgeon . Patients were review ed 1 , 3 , and 7 days postoperatively to assess bleeding . Eighty-two of the 85 patients encountered no postoperative problems . Two patients in group A and one in group B had minor postoperative bleeds that required minor ambulatory intervention to control . This study shows that a 2-day postoperative course of a 4.8 % tranexamic acid mouthwash is as equally effective as a 5-day course in controlling haemostasis post-dental extraction s in patient 's anticoagulated with warfarin OBJECTIVE To estimate the 3-month cumulative incidence of thromboembolism ( TE ) , bleeding , and death among consecutive patients with nonvalvular atrial fibrillation ( AF ) who were receiving long-term anticoagulation therapy and were referred to the Thrombophilia Center at Mayo Clinic for periprocedural anticoagulation management . PATIENTS AND METHODS In a prospect i ve cohort study of consecutive patients receiving long-term anticoagulation therapy who were referred to the Thrombophilia Center for periprocedural anticoagulation management over the 7-year period , January 1 , 1997 , to December 31 , 2003 , 345 patients with nonvalvular AF were eligible for inclusion . Warfarin was stopped 4 to 5 days before and was restarted after surgery as soon as hemostasis was assured . The decision to provide bridging therapy with heparin was individualized and based on the estimated risks of TE and bleeding . RESULTS The 345 patients with AF ( mean + /- SD age , 74+/-9 years ; 33 % women ) underwent 386 procedures . Warfarin administration was not interrupted for 44 procedures . Periprocedural heparin was provided for 204 procedures . Patients receiving heparin were more likely to have prior TE ( 43 % vs 24 % ; P<.001 ) and a higher CHADS2 ( congestive heart failure , hypertension , age , diabetes , stroke ) score ( 2.2 vs 1.9 ; P=.06 ) . Four patients had 6 episodes of TE ( 3 strokes and 3 acute coronary episodes ; TE rate , 1.1 % ; 95 % confidence interval , 0.0%-2.1 % ) . Nine patients had 10 major bleeding events ( major bleeding rate , 2.7 % ; 95 % confidence interval , 1.0%-4.4 % ) . There were no deaths . Neither bleeding nor TE rates differed by anticoagulant management strategy . CONCLUSION The 3-month cumulative incidence of TE and bleeding among patients with AF in whom anticoagulation was temporarily interrupted for an invasive procedure was low and was not significantly influenced by bridging therapy Objective : The management of anticoagulated patients with warfarin during dental extraction is an intricate issue . We carefully design ed the current study so that the amount of bleeding was measured with objective methods and the data from the same patient in different dental extraction appointments could be compared , eliminating the bleeding diathesis differences of patients . Methods : This prospect i ve and controlled study was conducted in 36 adult patients with prosthetic valve requiring multiple tooth extraction s. The first dental extraction was performed without the discontinuation of warfarin therapy , and the second procedure was performed with a discontinuation of warfarin and bridging with low-molecular weight heparin ( LMWH ) . The two dental extraction protocol s in the same patient group were compared . The total amount of bleeding was calculated as the difference between the weights of gauze swabs used before and after the tamponade ; the number of gauze swabs used for bleeding control in the first 48 h was recorded . Result : The median number of used gauze swabs was 2.5 ( IQR : 1–5 ) and 3.0 ( IQR : 2–7 ) in the first and second dental extraction procedures , respectively . The median bleeding time was 50.0 ( IQR : 20–100 ) in the first procedure compared with 60.0 ( IQR : 40–140 ) min in the second procedure . The mean amounts of bleeding were 2194±1418 mg in the first dental extraction procedure and 2950±1694 mg in the second dental extraction procedure . The median number of used gauze swabs , the median bleeding time , and the mean amount of bleeding were statistically higher in the second dental extraction procedure ( p<0.001 ) . Conclusion : Continued warfarin treatment at the time of dental extraction s reduces the total amount of bleeding compared with bridging therapy in patients with prosthetic valves BACKGROUND Patients on therapeutic anticoagulation are at risk of bleeding from minor oral surgical sites . When the anticoagulant regime is modified to prevent the risk of bleeding , this at the same time predisposes the patient to risks of the medical condition for which they are being treated . METHODS A total of 70 patients who were on warfarin treatment requiring minor oral surgical procedures were treated in the Oral Surgery Department . A control group of 35 had their warfarin stopped prior to the minor oral surgical procedure . The other 35 formed the study group . Patients with an International Normalized Ratio outside the therapeutic range of 2 - 4 , or with history of liver disease or on drugs affecting liver function were excluded from the study . Any incidences of post-operative bleeding were recorded . RESULTS None of the patients in either control or study group had any serious bleeding complications . CONCLUSION The data suggest that patients can safely undergo routine minor oral surgical procedures without alterations of their therapeutic anticoagulation regime We found no prospect i ve studies on dental extraction in anticoagulated patients in the literature , even though most authors suggest that there is no need to change anticoagulant treatment and to utilize a local haemostatic measure after extraction . In the present study , we have verified the incidence of bleeding complications after dental extraction in a group of 250 consecutive anticoagulated patients . Two hundred and fifty non-anticoagulated subjects requiring dental extraction represented the control group . In all patients , anticoagulant treatment was not changed ( International Normalized Ratio , 1.8–4 ) and local haemostatic measures ( fibrin sponge , silk suture and a gauze saturated with tranexamic acid ) were used . All procedures were performed in an outpatient clinic setting . We registered four bleeding complications in the group of anticoagulated patients and three in the control group . The difference of bleeding complications in the two groups was not statistically different ( relative risk , 1.14 ; 95 % confidence interval , 0.29–6.04 ; P = 0.7 ) . None of the post-operative late bleeding required hospitalization and /or blood transfusions , and further local measures were sufficient to stop the bleeding . The protocol proposed in the present study makes dental extraction s in anticoagulated patients possible on an outpatient basis with a cost reduction for the community and minor discomfort for the patients Background — Dabigatran reduces ischemic stroke in comparison with warfarin ; however , given the lack of antidote , there is concern that it might increase bleeding when surgery or invasive procedures are required . Methods and Results — The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the R and omized Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) trial treated with dabigatran and warfarin . Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures , considering only the first procedure for each patient . A total of 4591 patients underwent at least 1 invasive procedure : 24.7 % of patients received dabigatran 110 mg , 25.4 % received dabigatran 150 mg , and 25.9 % received warfarin , P=0.34 . Procedures included : pacemaker/defibrillator insertion ( 10.3 % ) , dental procedures ( 10.0 % ) , diagnostic procedures ( 10.0 % ) , cataract removal ( 9.3 % ) , colonoscopy ( 8.6 % ) , and joint replacement ( 6.2 % ) . Among patients assigned to either dabigatran dose , the last dose of study drug was given 49 ( 35–85 ) hours before the procedure on comparison with 114 ( 87–144 ) hours in patients receiving warfarin , P<0.001 . There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran 110 mg ( 3.8 % ) or dabigatran 150 mg ( 5.1 % ) or warfarin ( 4.6 % ) ; dabigatran 110 mg versus warfarin : relative risk , 0.83 ; 95 % CI , 0.59 to 1.17 ; P=0.28 ; dabigatran 150 mg versus warfarin : relative risk , 1.09 ; 95 % CI , 0.80 to 1.49 ; P=0.58 . Among patients having urgent surgery , major bleeding occurred in 17.8 % with dabigatran 110 mg , 17.7 % with dabigatran 150 mg , and 21.6 % with warfarin : dabigatran 110 mg ; relative risk , 0.82 ; 95 % CI , 0.48 to 1.41 ; P=0.47 ; dabigatran 150 mg : relative risk , 0.82 ; 95 % CI , 0.50 to 1.35 ; P=0.44 . Conclusions — Dabigatran and warfarin were associated with similar rates of periprocedural bleeding , including patients having urgent surgery . Dabigatran facilitated a shorter interruption of oral anticoagulation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600 OBJECTIVES This prospect i ve clinical comparative study aim ed to analyze the postoperative bleeding risk of patients continuing their anticoagulation therapy ( AT ) and undergoing implant surgery and bone grafting procedures . MATERIAL S AND METHODS The treatments ranged from the insertion of single or multiple dental implants over implant exposures to sinus floor augmentation and vertical and /or lateral bone grafting with autologous bone grafts . The patients of the test groups ( AT groups ) were treated with platelet aggregation inhibitors ( PAIs ) , Vitamin-K inhibitors , Vitamin-K inhibitor withdrawal bridged with heparin ( LMWH ) , or new/direct oral anticoagulants ( NOACs/DOACs ) . Patients of the control group were non-anticoagulated ( non-AT group ) . Surgical procedures were performed in the same manner in all groups . Pre , intra , and postoperative data concerning the treatment , extent of the surgery and bleedings was recorded and statistically evaluated . RESULTS There were seven postoperative bleedings in 564 patients ( 1.2 % ) , four in the AT groups ( 3.4 % ) , and three in the non-AT group ( 0.6 % ) . No thromboembolic complication occurred in the whole observation period . The invasiveness of the surgical procedure had no statistically significant effect on bleeding frequencies . Patients taking Vitamin-K inhibitors had a significantly higher risk of a postoperative bleeding compared to patients without any AT ( P = 0.038 ) . Two patients were hospitalized due to the severity of the bleeding as a pre caution ary measure ( one in the non-AT and one in the PAI group ) . All bleedings were easily controllable with local hemostatic measures . There was no postoperative bleeding recorded for patients taking DOACs . CONCLUSIONS Anticoagulation therapy should be continued in patients undergoing implant surgery and bone grafting procedures avoiding thromboembolic complications . Surgeons should always apply the most minimally invasive approach to reduce postoperative risks and be able to apply local hemostatic measures in terms of a bleeding complication PURPOSE To evaluate postoperative bleeding and thromboembolic complications during dental extraction s in anticoagulated patients , using 2 different protocol s. PATIENTS AND METHODS In total , 214 anticoagulated patients in need of simple dental extraction s were r and omized into 2 groups . Group A consisted of 109 patients on continuous oral anticoagulation therapy ( OAT ) , with a mean international normalized ratio ( INR ) of 2.45 + /- 0.54 . Local hemostasis in these patients was achieved with resorbable collagen sponges , without wound suturing . Group B consisted of 105 patients on bridging therapy with low-molecular-weight heparin ( nadroparin-calcium ) , with a mean INR of 1.26 + /- 0.11 on the day of the procedure . Neither local hemostatic agents nor suturing of the wound was used in these patients . RESULTS Eight ( 7.34 % ) patients in group A and 5 ( 4.76 % ) patients in group B manifested post extraction al bleeding , without statistical significance ( chi(2 ) , Yates ' = 0.253 , P > .05 ) . All cases of hemorrhage were mild and easily controlled using local hemostatic measures . None of the participants in either group experienced thromboembolic complications . CONCLUSIONS In patients receiving OAT with an INR < or=4.0 , simple dental extraction s can be performed safely without interruption or modification of OAT , using local hemostatic measures . Suturing of the wound should be reserved for cases with a greater extent of surgical trauma , and when primary hemostasis is insufficient . There is no need for bridging therapy with low-molecular-weight heparin in patients undergoing minor dentoalveolar procedures , although this approach can be used in patients with major oral surgical interventions OBJECTIVE The objective of this study was to compare the use of a resorbable oxycellulose dressing with a fibrin adhesive for the prevention of post extraction hemorrhage in patients taking anticoagulants . STUDY DESIGN A control group of 26 patients with a preoperative international normalized ratio ( INR ) in the range of 2.0 to 4.2 had extraction s performed with the use of local anesthesia and the socket(s ) dressed with a resorbable oxycellulose dressing and sutured with a resorbable suture . The study group with a comparable INR range of 2.1 to 4.1 was treated in a similar manner , except the sockets were dressed with a fibrin adhesive . RESULTS No discernible difference in the postoperative outcome with regard to hemorrhage was noted . Postoperative pain was reported more frequently in the group that used a resorbable oxycellulose dressing . Only 1 patient had significant postoperative bleeding . CONCLUSIONS This study shows that in patients receiving warfarin whose INR is within the therapeutic range , the fibrin adhesive is as effective as the resorbable oxycellulose dressing in preventing post extraction hemorrhage BACKGROUND Significant uncertainty surrounds the treatment of patients who must discontinue warfarin sodium therapy before an invasive procedure . In part , the uncertainty results from the lack of published information about the risk of thromboembolism associated with short-term warfarin therapy interruption . We aim ed to assess the frequency of thromboembolism and bleeding within a large cohort of patients whose warfarin therapy was temporarily withheld for an outpatient invasive procedure . METHODS This prospect i ve , observational cohort study was performed at 101 sites ( primarily community-based physician office practice s ) in the United States . Enrollment was conducted from April 4 , 2000 , to March 6 , 2002 . The main outcome measures were thromboembolism or clinical ly significant hemorrhage within 30 days of warfarin therapy interruption . RESULTS A total of 1293 episodes of warfarin therapy interruption in 1024 individuals were included . The mean ( SD ) patient age was 71.9 ( 10.6 ) years ; 438 ( 42.8 % ) were female . The most common indications for anticoagulant therapy were atrial fibrillation ( n=550 ) , venous thromboembolism ( n=144 ) , and mechanical heart valve ( n=132 ) . The most common procedures were colonoscopy and oral and ophthalmic surgery . Perioperative heparin or low-molecular-weight heparin was used in only 8.3 % of cases overall . Seven patients ( 0.7 % ; 95 % confidence interval [ CI ] , 0.3%-1.4 % ) experienced postprocedure thromboembolism within 30 days . None of the 7 patients who experienced thromboembolism received periprocedural bridging therapy . Six patients ( 0.6 % ; 95 % CI , 0.2%-1.3 % ) experienced major bleeding , whereas an additional 17 patients ( 1.7 % ; 95 % CI , 1.0%-2.6 % ) experienced a clinical ly significant , nonmajor bleeding episode . Of these 23 patients who had bleeding episodes , 14 received periprocedural heparin or low-molecular-weight heparin . The duration of warfarin therapy interruption was variable ; however , more than 80 % of patients had warfarin therapy withheld for 5 days or fewer . CONCLUSIONS For many patients receiving long-term anticoagulation who need to undergo a minor outpatient intervention , a brief ( < or = 5 days ) periprocedural interruption of warfarin therapy is associated with a low risk of thromboembolism . The risk of clinical ly significant bleeding , even among out patients undergoing minor procedures , should be weighed against the thromboembolic risk of an individual patient before the administration of bridging anticoagulant therapy Objectives To examine the consequences of temporary withdrawal of warfarin and /or suturing on bleeding and healing pattern following dental extraction s. Methods Two hundred and fourteen patients on long-term oral anticoagulation ( warfarin ) therapy scheduled for dental extraction were r and omly divided into four groups : no suturing and discontinued ( group 1 ) or continued warfarin ( group 2 ) , and suturing and discontinued ( group 3 ) or continued warfarin ( group 4 ) . International normalised ratio ( INR ) was determined at different time points ( baseline , days 1 , 3 and 7 ) . Results Discontinuing warfarin reduced INR level significantly at day 1 , which subsequently reached < 1.5 in 96 out of 104 patients ( group 1 and 3 ) . Statistical comparisons among the different treatment groups did not reveal any significant difference regarding bleeding status or healing pattern . Interestingly , patients who received sutures showed higher but insignificant incidence of bleeding postoperatively compared to their respective controls . Conclusion Dental extraction s may be safely performed for patients on anticoagulation therapy provided the INR level is kept < 3.0 and effective measures of local haemostasis are administered . The decision to suture should be made on case-by-case basis , as the trauma associated with soft tissue h and ling might outweigh its advantages in certain situations like simple extraction PURPOSE To evaluate the current practice of oral and maxillofacial surgeons in Michigan regarding perioperative warfarin therapy and dentoalveolar surgery in defined procedure risk groups . MATERIAL S AND METHODS Surveys were distributed to all surgeons ( n = 188 ) registered with the Michigan Society of Oral and Maxillofacial Surgeons . Low/moderate/high surgery risk groups were defined based on retrospective data accumulated for procedures on pretransplant liver failure patients . We requested the surgeon 's maximum tolerated International Normalized Ratio ( INR ) for each risk group . In addition , surgeons were asked if their routine practice for each group included continuation or discontinuation of therapeutic warfarin perioperatively . RESULTS A 72.6 % response rate was achieved . The average maximum INR cutoff values for the various risk groups were : low , 2.68 ; moderate , 2.28 ; and high , 2.01 . Routine discontinuation of warfarin occurred in these groups 23.6 % , 48.8 % , and 70.5 % , respectively . Using a paired t test , these results showed statistically significant differences in patient management practice s ( P < .001 ) between the low , moderate , and high risk groupings . CONCLUSION Lack of uniformity exists regarding warfarin therapy and dentoalveolar surgery . No studies to date involve significant numbers of moderate/high risk procedures to provide evidence -based support of safety with maintenance of therapeutic INR . For moderate or high risk procedures , the majority of surgeons prefer warfarin discontinuation with minimally therapeutic or subtherapeutic levels , a practice that secondarily increases risk for thromboembolism . Based on these preliminary data , we believe a prospect i ve trial to eluci date stronger management guidelines for both the moderate and high risk surgery population is indicated BACKGROUND Rivaroxaban is a new oral anticoagulant ( NOAC ) that can be prescribed in a fixed dose , making regular monitoring and dose adjustments unnecessary . It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists ( LMWH/VKA ) for the ( extended ) treatment of venous thromboembolism in the EINSTEIN studies . Nevertheless , there is a need for information regarding the clinical impact of ( major ) bleeding events with NOACs such as rivaroxaban . OBJECTIVES A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA . METHODS Two investigators performed a blinded classification of major bleeding using a priori defined criteria . During the EINSTEIN studies , data concerning the clinical course and measures applied were prospect ively collected for each major bleed . RESULTS Treatment with LMWH/VKA caused more major bleeding events ( 1.7 % ) than rivaroxaban ( 1.0 % ; hazard ratio , 0.54 ; 95 % confidence interval [ CI ] , 0.37 - 0.79 ) . Major bleeding events during rivaroxaban therapy had a milder presentation ( 23 % were adjudicated to the worst categories vs. 38 % for LMWH/VKA ; hazard ratio or HR , 0.35 ; 95 % CI , 0.17 - 0.74 ; P = 0.0062 ) . The clinical course was severe in 25 % of all major bleeding events associated with rivaroxaban , compared with 33 % of LMWH/VKA-associated bleeds ( HR , 0.46 ; 95 % CI , 0.22 - 0.96 ; P = 0.040 ) . CONCLUSIONS Rivaroxaban-associated major bleeding events occurred less frequently , had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA BACKGROUND After a vitamin K antagonist ( VKA ) overdose , 1 - 2 mg of oral vitamin K can lower the International Normalized Ratio ( INR ) to the therapeutic range . OBJECTIVE To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery . METHODS Patients on long-term VKAs were r and omized either to heparin bridging after the last VKA dose on day -5 before surgery ( group H ) or to VKA treatment until day -2 , followed by 1 mg of oral vitamin K on the day before surgery ( group K ) . Blood clotting variables were assessed on days -5/-2 , 1 and 0 , and postoperatively . If the target INR was not achieved 2 h before incision , surgery was deferred or performed after injection of prothrombin complex concentrate ( PCC ) . RESULTS In 30 of 94 included patients , baseline INR was outside the chosen range ( 18 , INR < 2 ; 12 , INR > 3.5 ) , leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index , VKA treatment duration and indication , scheduled surgery , preoperative and postoperative hemoglobin , and blood loss . The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients ( 66 % ) . Surgery was postponed or performed after PCC injection in 12 of these 20 patients . CONCLUSIONS Oral vitamin K ( 1 mg ) can not substitute for heparin bridging before surgery . In addition , one-third of patients on VKAs were exposed to a risk of bleeding ( overdose ) or thrombosis ( underdose ) , thus highlighting the need for new oral anticoagulants BACKGROUND / AIM Patients receiving long-term oral anticoagulant therapy pose a clinical challenge during invasive dental procedures . The goal of this study was to compare different local hemostatic modalities after tooth extraction in patients receiving chronic Vitamin-K antagonist therapy . METHODS Totally 90 patients with International Normalized Ratio ( INR ) ≤ 3.0 requiring simple extraction of one or two teeth were r and omized into three groups , 30 patients in each group . The patients with the mean INR value of 2.35 ± 0.37 , in whom extraction wound was sutured comprised the group A. In the group B with the mean INR of 2.43 ± 0.4 , local hemostasis was achieved by placing absorbable gelatin sponges into the wound without suturing . The group C consisted of the patients with the mean INR of 2.36 ± 0.34 in whom neither gelatin sponge nor suturing were used for providing local hemostasis . Bleeding was registered as an event if other than initial hemostatic measure was needed or additional oral surgeon intervention required . RESULTS The obtainded results show that 1 ( 3.3 % ) patient in the group A , 2 ( 6.7 % ) patients in the groups B and C manifested post- extraction bleeding . All cases of hemorrhage were easily solved with local hemostatic measures and all , except one case , were registered in the first two hours after the procedure until the dismissal . A difference between the groups was not statistically significant ( χ2 = .42 , p > 0.05 ) . CONCLUSION In therapeutically anticoagulated patients tooth extraction s can be safely performed without altering the dose of anticoagulant medication if efficient local hemostasis is provided . In most cases ; in patients with INR ≤ 3.0 after extraction of one or two teeth postoperative bleeding can be controlled with local pressure , without any additional local hemostatic measures OBJECTIVE To evaluate whether or not it is possible to perform oral surgery in patients on oral anticoagulant therapy ( OAT ) without stopping treatment . STUDY DESIGN A prospect i ve r and omized open-label study was design ed to evaluate the outcome of oral surgery in patients on OAT , operated upon in conditions of reduced international normalized ratio ( INR ) , compared with patients maintained in their usual therapeutic ranges of the prothrombin time INR . The INR target in the group with reduced OAT was 1.8 , and the INR target of the group without reduced OAT was 2.5 or more in carriers of artificial valves . RESULTS One hundred thirty-one patients on OAT were r and omized to reduced anticoagulation or to full anticoagulation , and 511 teeth were extracted by the same surgeon . Mild bleeding , but excessive enough to warrant adoption of supplementary local hemostatic measures , was observed in 10 cases ( 15.1 % ) in the reduced dosage group and in 6 cases ( 9.2 % ) in the unmodified dosage group , which was a nonsignificant difference . There were no thrombotic complications in either group . CONCLUSIONS This r and omized study shows that , using simple measures for local hemostasis , it is not necessary to reduce OAT in patients undergoing routine dental extraction PURPOSE This study assessed the risk associated with several schedules of perioperative treatment with coumadin in anticoagulated patients who underwent oral surgery . PATIENTS AND METHODS A prospect i ve , r and omized study compared bleeding complications with six perioperative schedules in 92 patients chronically treated with acenocoumarol . In three of the perioperative schedules , the dose was reduced before surgery and calcium heparin was added . In the other three , oral anticoagulation was not modified and heparin was not used . The groups also differed regarding the antifibrinolytic agents used and the postoperative measures applied . RESULTS Those schedules in which the oral anticoagulation was not modified preoperatively and an antifibrinolytic agent was applied locally both during and after surgery were not associated with a significantly higher odds ratio of bleeding complications than those in whom oral anticoagulation was reduced and calcium heparin was added preoperatively . CONCLUSIONS In orally anticoagulated patients who undergo oral surgery , schedules that maintain the oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic agent postoperatively for 2 days are safe , simple , and less troublesome PURPOSE Our goal was to evaluate the local hemostatic effect of n-butyl-2-cyanoacrylate ( Histoacryl ; B. Braun , Melsungen , Germany ) glue in warfarin-treated patients who undergo outpatient oral surgery without a change in their level of anticoagulation . MATERIAL S AND METHODS Thirty consecutive warfarin-treated patients r and omly assigned to study and control groups and 10 patients who had never been on anticoagulant therapy serving as the negative control group were included in this trial . Before multiple teeth extraction s , all patients had a prothrombin time and the international normalized ratio ( INR ) determined . To gain hemostasis and primary closure , gelatin sponge and multiple interrupted resorbable sutures were used in the control and negative control groups , and Histoacryl glue and the minimal number of interrupted resorbable sutures were used in the study group . Postoperatively , patients were to contact the oral surgeon if abnormal bleeding occurred . Patients who did not have postoperative bleeding were seen on the 10th postoperative day . Data were collected , and statistical differences in age and gender distributions , number of teeth extracted , INR levels , and bleeding that required treatment were analyzed with the Mantel-Haenzel test . Statistical significance was defined as a value of P < .05 . RESULTS Local hemostasis was obtained immediately in study patients and only after 10 to 20 minutes in the control and negative control patients . In relation to bleeding complications , there were no cases of postoperative bleeding requiring treatment in both the negative control patients and study patients . In the control patients , 5 cases had postoperative spontaneous bleeding that required treatment . This difference was statistically significant . No patient had wound infection and the healing process appeared to be normal . CONCLUSION Multiple extraction s can be performed in patients taking oral anticoagulant therapy without a change in their level of anticoagulation provided an efficient local hemostatic measure is instituted . And , in this regard , Histoacryl glue , used as a topical adhesive over approximated wound edges , is an effective and easily applicable local hemostatic for oral surgery in such patients Following favourable results from a previous study , a large , multicentre , prospect i ve , case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy ( OAT ) . Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure . In the warfarin-treated group , the oral anticoagulant regimen was maintained unchanged , such that the patients had an International Normalised Ratio ranging between 1.8 and 4 , and local haemostatic measures ( i.e. fibrin sponges , silk sutures and gauzes saturated with tranexamic acid ) were adopted . All the procedures were performed in an outpatient setting . Seven bleeding complications occurred in the OAT group and four in the control group ; the difference in the number of bleeding events between the two groups was not statistically significant ( OR=1.754 ; 95 % CI 0.510 - 6.034 ; p=0.3727 ) . No post-operative late bleeds requiring hospitalisation and /or blood transfusions were recorded , and the adjunctive local haemostatic measures were adequate to stop the bleeding . The results of our protocol applied in this large , multicenter study show that dental extraction s can be performed easily and safely in anticoagulated out patients without any modification of the ongoing anticoagulant therapy , thus minimising costs and reducing discomfort for patients PURPOSE The aim of this prospect i ve study was to compare the effectiveness of a 4.8 % tranexamic acid mouthwash versus an autologous fibrin glue preparation to control hemostasis in patients therapeutically anticoagulated with warfarin who required dental extraction s without interruption of their treatment . PATIENTS AND METHODS The 49 patients who underwent 152 dental extraction s were r and omly allocated to 2 groups : Group A were required to rinse with 10 mL of a 4.8 % tranexamic acid solution 4 times a day for 7 days postoperatively . Group B received autologous fibrin glue intraoperatively . The international normalized ratio was measured on the day of the procedure . All procedures were performed on an ambulatory basis by the same surgeon . RESULTS Of the 49 patients , 2 presented with postoperative bleeding ( 4 % ) . Both patients were from the autologous fibrin glue group and were found to have grossly elevated international normalized ratios on the day of the bleeding that was unaccounted for . CONCLUSIONS This study supports the consensus that dental extraction s can be performed without modification of oral anticoagulant treatment . Local hemostasis with an absorbable oxidized cellulose mesh , tranexamic acid , and sutures is the more cost efficient of the 2 methods compared ; however , autologous fibrin glue has an important role in patients unable to use a mouthwash effectively Temporary discontinuation of high-intensity oral anticoagulant treatment is not recommended in patients under going dental surgery . This policy is not based on solid data from r and omized clinical trials but on expert consensus . The alternative , i.e. , to continue treatment and treat patients with tranexamic acid mouthwash , often is not applicable . A prospec tive cohort study was carried out to evaluate bleeding and thromboembolic complications in patients bearing prosthetic heart valves and registering International Normalized Ratio ( INR ) values between 2.0 and 4.5 , who underwent dental pro cedures after a 2-day suspension of warfarin treatment . One hundred four consecutive patients receiving high-intensity an ticoagulation underwent 123 dental procedures after 2 days ' warfarin withdrawal . No major bleeding complications oc curred in the week after the procedure ; minor bleeding requir ing local measures occurred in two patients . No thromboem bolic events and no cases of bacterial endocarditis were re corded in the 3 months after the procedure . A mean decrease in INR by approximately 1.0 U ( from 2.95 ± 0,59 to 1.87 ± 0,46 ) occurred after 2 days ' warfarin suspension . Seven days after reinitiation of warfarin , INR values returned to the therapeutic range in 90 % of cases . The calculated average time spent at INR less than 2.0 ( critical value ) was 28 hours . Two days ' warfarin suspension is a simple and safe policy for patients with prosthetic heart valves undergoing dental surgery Background and Objective : Patients with cardiogenic sources of embolism may be at increased risk of cerebral infa rct ion when anticoagulation therapy is suspended for surgical procedures . The purpose of this study was to determine frequency of cardioembolic cerebral infa rct ion during periprocedural warfarin withdrawal . Methods : Retrospective analysis of prospect i ve cerebral infa rct ion registry data from two tertiary medical centers . Results : Over a 12-month period , 14 cases of cardioembolic cerebral infa rct ion occurring during the period of warfarin withdrawal for a medical procedure were observed , accounting for 7.1 % of the 197 cardioembolic cerebral infa rct ions encountered . Across all patients , cerebral infa rct ions developed an average of 5.4 days after the last dose of warfarin ( range 3–8 ) . Among the 14 patients ( 8 males and 6 females ) with warfarin cessation-related infa rcts , age ranged from 54 to 91 years . Each had been on chronic anticoagulation with warfarin for more than 1 year . Retrospective analysis suggested that all these cerebral infa rct ions had been potentially preventable . In each case , either the planned procedure did not require discontinuation of warfarin or , when withdrawal was required , no bridging , parenteral anticoagulation was provided to lessen the risk during the warfarin-free period . Conclusion : Patients at high risk of cardioembolic cerebral infa rct ion may benefit from more intensive management strategies to reduce cerebral infa rct ion risk during periprocedural periods A r and omized controlled trial was set up to investigate whether patients who were taking warfarin and had an International Normalised Ratio ( INR ) within the normal therapeutic range require cessation of their anticoagulation drugs before dental extraction s. Of 109 patients who completed the trial , 52 were allocated to the control group ( warfarin stopped 2 days before extraction ) and 57 patients were allocated to the intervention group ( warfarin continued ) . The incidence of bleeding complications in the intervention group was higher ( 15/57 , 26 % ) than in the control group ( 7/52 , 14 % ) but this difference was not significant . Two patients in the study required hospital review for bleeding and all other episodes of bleeding were controlled by patients at home . Continuing warfarin when the INR is < 4.1 may lead to an increase in minor post- extraction bleeding after dental extraction s but we found no evidence of an increase in clinical ly important bleeding . As there are risks associated with stopping warfarin , the practice of routinely discontinuing it before dental extraction s should be reconsidered Various clinical protocol s for the management of warfarinised patients needing dental extraction s have been suggested . This study was design ed to compare two approaches in the management of these patients . A control group of 32 patients had their warfarin treatment stopped for 2 - 3 days prior to having dental extraction s , result ing in a reduction in the average preoperative international normalised ratio ( INR ) from 2.6 to 1.6 . The study group of 33 patients did not have their anticoagulant treatment altered before extraction s , and had an average preoperative INR of 2.7 . All patients were treated under local analgesia on an outpatient basis , and local measures -consisting of Surgicel pack and sutures-were used in all cases to control postoperative bleeding from extraction sockets . None of the patients had any immediate postoperative bleeding , and only 1 patient from each group had mild delayed haemorrhage , which was easily controlled with local measures . It is proposed that , provided the INR is within the therapeutic range of 2.0 to 4.0 and local measures are used to control postoperative bleeding , there is no justification in altering warfarin treatment prior to dental extraction s in these patients , and thereby exposing them to the risk of thromboembolism |
11,277 | 25,752,762 | LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED .
LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week . | OBJECTIVE To describe the efficacy and safety of lisdexamfetamine dimesylate ( LDX ) for the treatment of binge eating disorder ( BED ) .
DATA SYNTHESIS LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED .
The recommended dose range is 50 - 70 mg/day . | The relative bioavailability of oral lisdexamfetamine dimesylate , a prodrug of d-amphetamine , and active d-amphetamine was assessed in an open-label , single-dose , 3-treatment , 3-period , r and omized , crossover study in 18 healthy adult volunteers . Following a fast of at least 10 hours , subjects were administered an intact capsule of 70 mg lisdexamfetamine , a solution containing the capsule contents , or an intact capsule with a high-fat meal . St and ard meals started 4 hours following lisdexamfetamine administration . Blood sample s were taken predose ( 0 hours ) and 0.5 to 72 hours postdose , and the concentrations of d-amphetamine and lisdexamfetamine were measured . AUC and C(max ) for d-amphetamine were similar when lisdexamfetamine 70 mg was administered to healthy adults in the fed or fasted state . The AUC of intact lisdexamfetamine was similar when the latter was taken without food or in solution , but C(max ) was lower when lisdexamfetamine was administered with food . The t(max ) of d-amphetamine and intact lisdexamfetamine was similar when taken in solution or in the fasted state but was about 1 hour longer when taken with food . Adverse events were typical for amphetamine products . These findings indicate that food does not have a significant effect on d-amphetamine or lisdexamfetamine bioavailability in healthy adults and that lisdexamfetamine was well tolerated Abstract Lisdexamfetamine dimesylate ( LDX ) is the first prodrug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder . A single-centre , double-blind , r and omised , placebo-controlled , 6-period crossover study evaluated the abuse potential of single oral doses of 50 , 100 ( equivalent to 40 mg d-amphetamine ) , and 150 mg LDX , 40 mg d-amphetamine and 200 mg diethylpropion in 36 individuals with a history of stimulant abuse . On the primary abuse liability measure , maximum change of the Drug Rating Question naire-Subject Liking Scale compared with placebo , d-amphetamine and diethylpropion showed significant differences of 4.5 and 4.0 units , respectively ( P < 0.001 for both vs placebo ) . LDX , administered at 50 , 100 and 150 mg , showed nonsignificant differences of 2.0 and 2.1 units , respectively , at the two lower doses but a significant ( P < 0.001 vs placebo ) difference of 6.1 units at the highest dose . Subjects significantly favoured d-amphetamine 40 mg versus LDX 100 mg ( 2.4 units difference ; P < 0.05 ) . There was no significant difference in liking scores between d-amphetamine 40 mg and LDX 150 mg . Drug Rating Question naire-Subject Feel-Drug-Effect score was significantly lower for 100 mg LDX than for 40 mg d-amphetamine . There were no statistically significant differences between LDX and diethylpropion hydrochloride , a Schedule IV amphetamine-like stimulant , on abuse-related liking scores . Cardiovascular responses of LDX and d-amphetamine were similar at equivalent doses . In conclusion , at an equivalent amount of amphetamine base taken orally , LDX 100 mg had attenuated responses on measures of abuse liability compared with immediate-release d-amphetamine 40 mg . Abuse-related liking scores of LDX at a dose corresponding to a 50 % higher amphetamine base ( LDX 150 mg ) were similar to d-amphetamine 40 mg ABSTRACT Objective : To evaluate the pharmacokinetics of lisdexamfetamine dimesylate ( LDX ; Vyvanse * ) in fasting healthy adult volunteers . Background : LDX is the first pro-drug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder . LDX was developed with the goal of providing an extended effect that is consistent throughout the day , with a reduced potential for abuse , overdose toxicity , and drug tampering . Methods : This was an open-label , multiple-dose phase 1 study . LDX 70 mg/d was administered in the morning to 12 subjects for 7 days . Twenty blood sample s were drawn during the study . Descriptive statistics were used for pharmacokinetic parameters . Results : Based on Cmin , steady-state d-amphetamine concentration ( 20.6 ng/mL ) was reached by day 5 , whereas LDX was undetectable , and 95 % of the d-amphetamine was eliminated within 48 hours following the final dose on day 7 . At steady state , d-amphetamine achieved a mean ± st and ard deviation Cmax of 90.1 ± 29.6 ng/mL , with a median Tmax of 3.0 hours . The AUC0–inf for d-amphetamine was 1453 ± 645.7 ng.h/mL.Complete elimination of the pro-drug occurred approximately 6 hours following the final dose on day 7 . Adverse events were mild to moderate and similar to other oral amphetamines . Conclusions : This study describes the steady-state pharmacokinetics of LDX , a new pro-drug stimulant . Possible study limitations include an open-label design and a small sample size The pharmacokinetics of lisdexamfetamine dimesylate , a long-acting prodrug stimulant , and its active moiety , d-amphetamine , including dose-proportionality and variability , were assessed in 20 healthy adults . Subjects received a single dose , sequentially , of 50 , 100 , 150 , 200 , and 250 mg of lisdexamfetamine dimesylate . Plasma lisdexamfetamine dimesylate and d-amphetamine were measured before dosing and 0.25 to 96 hours postdose . Dose-proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined . Safety assessment s included adverse events . All 20 subjects received 50 and 100 mg while 18 , 12 , and 9 subjects received 150 , 200 , and 250 mg of lisdexamfetamine dimesylate , respectively . Ten subjects were discontinued during the study for prespecified stopping rules ( 2 consecutive hourly readings of blood pressure : systolic > 160 mm Hg or diastolic > 100 mm Hg ) . Mean maximum observed plasma concentration ( C(max ) ) and area under the concentration-time curve from time 0 to infinity ( AUC(0-∞ ) ) increased linearly and dose-dependently for d-amphetamine . Median time to C(max ) ranged from 4 to 6 hours for d-amphetamine and 1.0 to 1.5 hours for lisdexamfetamine dimesylate . Intersubject and intrasubject variability over doses from 50 to 150 mg was low ( < 20 % ) for both C(max ) and AUC(0-∞ ) . Adverse events included nausea , dizziness , headache , psychomotor hyperactivity , and dysuria . These findings indicate that the pharmacokinetic parameters of d-amphetamine were dose-proportional and predictable over a wide range of lisdexamfetamine dimesylate doses IMPORTANCE Binge-eating disorder ( BED ) , a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome , lacks approved pharmacotherapies . OBJECTIVE To examine the efficacy and safety of lisdexamfetamine dimesylate , a dextroamphetamine prodrug , to treat moderate to severe BED . DESIGN , SETTING , AND PARTICIPANTS We performed a r and omized , double-blind , parallel-group , forced dose titration , placebo-controlled clinical trial at 30 sites from May 10 , 2011 , through January 30 , 2012 . Safety and intention-to-treat analyses included 259 and 255 adults with BED , respectively . INTERVENTIONS Lisdexamfetamine dimesylate at dosages of 30 , 50 , or 70 mg/d or placebo were provided to study participants ( 1:1:1:1 ) . Dosages were titrated across 3 weeks and maintained for 8 weeks . We followed up participants for a mean ( SD ) of 7 ( 2 ) days after the last dose . MAIN OUTCOMES AND MEASURES We assessed the change in binge-eating ( BE ) behaviors measured as days per week ( baseline to week 11 ) with a mixed-effects model using transformed log ( BE days per week ) + 1 . Secondary measures included BE cessation for 4 weeks . Safety assessment s included treatment-emergent adverse events , vital signs , and change in weight . RESULTS At week 11 , log-transformed BE days per week decreased with the 50-mg/d ( least squares [ LS ] mean [ SE ] change , -1.49 [ 0.066 ] ; P = .008 ) and 70-mg/d ( LS mean [ SE ] change , -1.57 [ 0.067 ] ; P < .001 ) treatment groups but not the 30-mg/d treatment group ( LS mean [ SE ] change , -1.24 [ 0.067 ] ; P = .88 ) compared with the placebo group . Nontransformed mean ( SD ) days per week decreased for placebo and the 30- , 50- , and 70-mg/d treatment groups by -3.3 ( 2.04 ) , -3.5 ( 1.95 ) , -4.1 ( 1.52 ) , and -4.1 ( 1.57 ) , respectively . The percentage of participants achieving 4-week BE cessation was lower with the placebo group ( 21.3 % ) compared with the 50-mg/d ( 42.2 % [ P = .01 ] ) and 70-mg/d ( 50.0 % [ P < .001 ] ) treatment groups . The incidence of any treatment-emergent adverse events was 58.7 % for the placebo group and 84.7 % for the combined treatment group . In the treatment groups , 1.5 % of participants had serious treatment-emergent adverse effects . Events with a frequency of at least 5 % and changes in heart rate were generally consistent with the known safety profile . The mean ( SD ) change in body weight was -0.1 ( 3.09 ) , -3.1 ( 3.64 ) , -4.9 ( 4.43 ) , -4.9 ( 3.93 ) , and -4.3 ( 4.09 ) kg for the placebo group , the 30- , 50- , and 70-mg/d treatment groups , and the combined treatment groups , respectively ( P < .001 for each dose vs placebo group comparison in post hoc analysis ) . CONCLUSIONS AND RELEVANCE The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days , BE cessation , and global improvement . The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder . Further investigation of lisdexamfetamine in BED is ongoing . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01291173 The two specialty psychological therapies of CBT and IPT remain the treatments of choice for the full range of BED patients , particularly those with high levels of specific eating disorder psychopathology such as overvaluation of body shape and weight . They produce the greatest degree of remission from binge eating as well as improvement in specific eating disorder psychopathology and associated general psychopathology such as depression . The CBT protocol evaluated in the research summarized above was the original manual from Fairburn and colleagues . Fairburn has subsequently developed a more elaborate and sophisticated form of treatment , namely , enhanced CBT ( CBT-E ) for eating disorders . Initial research suggests that CBT-E may be more effective than the earlier version with bulimia nervosa and Eating Disorder Not Otherwise Specified patients . CBT-E has yet to be evaluated for the treatment of BED , although it would currently be the recommended form of CBT . Of relevance in this regard is that the so-called broad form of the new protocol includes 3 optional treatment modules that could be used to address more complex psychopathology in BED patients . One of the modules targeted at interpersonal difficulties is IPT , as described earlier in this chapter . Thus , the broader protocol could represent a combination of the two currently most effective therapies for BED . Whether this combined treatment proves more effective than either of the components alone , particularly for a subset of BED patients with more complex psychopathology , remains to be tested . CBT-E also includes a module design ed to address what Fairburn terms “ mood intolerance ” ( problems in coping with negative affect ) that can trigger binge eating and purging . The content and strategies of this mood intolerance module overlap with the emotional regulation and distress tolerance skills training of Linehan 's dialectical behavior therapy ( DBT ) . Two r and omized controlled trials have tested the efficacy of an adaptation of DBT for the treatment of BED ( DBT-BED ) featuring mindfulness , emotion regulation , and distress tolerance training . A small study by Telch and colleagues found that modified DBT-BED was more effective than a wait list control in eliminating binge eating . A second study showed that DBT-BED result ed in a significantly greater remission rate from binge eating at posttreatment than a group comparison treatment design ed to control for nonspecific therapeutic factors such as treatment alliance and expectations.50 This difference between the two treatments disappeared over a 12-month follow-up , indicating the absence of DBT-BED-specific influences on long-term outcomes . Both CBT and IPT have been shown to be more effective in eliminating binge eating than BWL in controlled , comparative clinical trials . Nonetheless , BWL has been effective in reducing binge eating and associated eating problems in BED patients in some studies and might be suitable for treatment of BED patients without high levels of specific eating disorder psychopathology . A finding worthy of future research is the apparent predictive value of early treatment response to BWL , indicating when BWL is likely to prove effective or not . No evidence supports the concern that BWL 's emphasis on moderate caloric restriction either triggers or exacerbates binge eating in individuals with BED . Initially , CBTgsh was recommended as a feasible first-line treatment that might be sufficient treatment for a limited subset of patients in a stepped care approach . More recent research , however , has shown that CBTgsh seems to be as effective as a specialty therapy , such as IPT , with a majority of BED patients . The subset of patients that did not respond well to CBTgsh in this research were those with a high level of specific eating disorder psychopathology , as noted . A plausible explanation for this moderator effect is that the original Fairburn CBTgsh manual does not include an explicit emphasis on body shape and weight concerns . Subsequent implementation of this treatment has incorporated a module that directly addresses overvaluation of body shape and weight . Future research should determine whether an exp and ed form of CBTgsh is suitable for the full range of patients with BED . CBTgsh is recommended as a treatment for BED on two other counts . First , its brief and focused nature makes it cost effective . Second , its structured format makes it more readily disseminable than other longer , multicomponent psychological therapies . It can be implemented by a wider range of treatment providers than more technically complex , time-consuming , and clinical expertise-dem and ing specialty therapies such as CBT-E and IPT . The latter evidence -based therapies are rarely available to patients with BED in routine clinical care setting s. Nevertheless , it must be noted that much of the research on CBTgsh to date has been conducted in an eating disorder specialty clinic setting . The degree to which the treatment can be adapted to a range of clinical service setting s remains to be determined . In addition , little is known about the specific provider qualifications and level of expertise required to implement CBTgsh successfully . Despite its brief and focal nature , specific provider skills regarding what and what not to address in treatment are required . Currently available pharmacologic treatments can not be recommended for treatment of BED . Aside from the inconsistent results of existing studies , the striking absence of controlled long-term evaluation of such treatment argues against its use . As summarized , the evidence -based treatments of CBT , IPT , and CBTgsh result in significant improvement and large treatment effects on multiple outcome measures aside from binge eating in overweight and obese patients . These include specific eating disorder psychopathology ( eg , overvaluation of body shape and weight ) , general psychopathology ( eg , depression ) , and psychosocial functioning . Moreover , these changes are typically well-maintained over 1 to 2 years of follow-up . The exception to this profile of improvement remains weight loss and its maintenance over time . These specialty psychological treatments do not produce weight loss , although successfully eliminating binge eating might protect against future weight gain . BWL consistently produces short-term weight loss , the extent of which has varied across different studies . Long-term weight loss has yet to be demonstrated , however . In this regard , the findings with obese patients with BED are not different than those on the treatment of obesity in general , in which there is little robust evidence of enduring weight loss effects of BWL |
11,278 | 31,897,307 | All the studies reported positive health outcomes following the intervention , including better self-management , increased patient – provider communication , improved medication adherence , and reduced disease symptoms .
Conclusion Current evidence suggests a low number of interventions with positive outcomes . | Background A high burden of non-communicable diseases ( NCDs ) is contributing to high mortality and morbidity in India .
Recent advancements in digital health interventions , including mHealth , eHealth , and telemedicine , have facilitated patient-centered care for NCDs .
Objective This systematic review aims to evaluate the current evidence on digital interventions for people living with NCDs in India and the outcomes of those interventions . | Background Mobile health ( mHealth ) has continuously been used as a method in behavioral research to improve self-management in patients with chronic diseases . However , the evidence of its effectiveness in chronic disease management in the adult population is still lacking . We conducted a systematic review to examine the effectiveness of mHealth interventions on process measures as well as health outcomes in r and omized controlled trials ( RCTs ) to improve chronic disease management . Methods Relevant r and omized controlled studies that were published between January 2005 and March 2016 were search ed in six data bases : PubMed , CINAHL , EMBASE , the Cochrane Library , PsycINFO , and Web of Science . The inclusion criteria were RCTs that conducted an intervention using mobile devices such as smartphones or tablets for adult patients with chronic diseases to examine disease management or health promotion . Results Of the 12 RCTs review ed , 10 of the mHealth interventions demonstrated statistically significant improvement in some health outcomes . The most common features of mHealth systems used in the review ed RCTs were real-time or regular basis symptom assessment s , pre-programed reminders , or feedbacks tailored specifically to the data provided by participants via mHealth devices . Most studies developed their own mHealth systems including mobile apps . Training of mHealth systems was provided to participants in person or through paper-based instructions . None of the studies reported the relationship between health outcomes and patient engagement levels on the mHealth system . Conclusions Findings from mHealth intervention studies for chronic disease management have shown promising aspects , particularly in improving self-management and some health outcomes Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers BACKGROUND In 2015 , India had an estimated 69.2 million people with diabetes and a national prevalence of 8.7 % . Evidence is mounting for the benefits of telemedicine in diabetes care , but remains limited on mobile-health ( m-Health ) interventions . INTRODUCTION This study assessed the impact of an m-Health diabetes platform on clinical outcomes , patient-reported outcomes , patient and provider satisfaction , and app usage . MATERIAL S AND METHODS This open-label , two-arm parallel study enrolled 91 people at 3 sites in India , aged 18 - 65 , with type 2 diabetes , and an A1c between 7.5 % and 12.5 % ( 58 - 113 mmol/mol ) . Participants were r and omly assigned 1:1 to m-Health or usual care and observed for 6 months . All received free visits , laboratory tests , transportation fees , and strips and lancets . Intervention participants received the m-Health app and a mobile phone data stipend . RESULTS A1c change was previously reported as statistically significant . Significantly more participants in intervention than control had improved medication adherence ( 39.0 % vs. 12.8 % ; p = 0.03 ) and increased frequency of blood glucose ( BG ) self-testing ( 39.0 % vs. 10.3 % ; p = 0.01 ) at 6 months from baseline . No other outcomes were significantly different . Among m-Health users , 75 % of participants actively used the app at week 24 . Participants entered 29,668 medications and 2,575 BG readings , sent 497 messages , and received 890 messages . Most participants ( 80 % ) were satisfied with all aspects of the app and all seven providers rated the software very acceptable . DISCUSSION Participants assigned to m-Health had increased medication adherence and frequency of BG testing compared with usual care participants . CONCLUSIONS This tool could be an effective way to exp and access to quality chronic disease care and improve outcomes Background : Mobile phone technology is being used worldwide to improve follow-ups in health care . Aim : Aim of the study is to evaluate whether the use of mobile technology will improve or not the follow-up of Indian patients from a community mental health center . Material s and Methods : Patients or caregivers having mobile phones and consenting for study were enrolled , and sociodemographic and clinical details of patients were taken . Participants were r and omized into two groups ( short message service [ SMS ] vs. non-SMS group ) . At first intervention level , a SMS was sent to SMS group ( not in non-SMS group ) 1 day before their appointment . At second-level intervention ( voice call level ) , patients from both groups who missed their first appointment were given a voice call requesting them to come for follow-up , and the reasons for first missed appointments ( MA ) were also elicited . The effect of these two intervention levels ( first SMS for SMS group and next voice calls for both groups ) on follow-up was evaluated . Results : A total of 214 patients were enrolled in the study . At first SMS intervention level of SMS group ( n = 106 ) , 62.26 % of participants reached appointment-on-time ( RA ) , while in the non-SMS/as usual group ( n = 108 ) , 45.37 % of patients RA . The difference of these groups is statistically significant . At second-level intervention ( voice call ) , 66 of 88 ( another 15 were unable to contact ) were came for follow-up consultation within 2 days of MA . Distance and diagnosis of alcohol dependence were significantly associated with MA . Social reasons were most common reasons for first MA . Conclusion : The use of mobile phone technology in an outpatient community psychiatric clinic improved follow-up significantly The purpose of this review was to determine whether mHealth interventions were effective in low- and middle-income countries in order to create a baseline for the evidence to support mHealth in developing countries . Studies were identified by search ing Medline on 02 October 2014 for articles published in the English language between January 2000 and September 2014 . Inclusion criteria were : 1 ) written in English , 2 ) completion of an mHealth intervention in a low or middle-income country , 3 ) measurement of patient outcomes , and 4 ) participants 18 years of age or older . 7,920 titles were review ed and 7 were determined eligible based on inclusion criteria . Interventions included a cluster r and omized trial , mixed methods study , retrospective comparison of an opt-in text message program , a two-arm proof of concept , single arm trial , a r and omized trial , and a single subject design . Five out of seven of the studies showed significant difference between the control and intervention . Currently there is little evidence on mHealth interventions in developing countries , and existing studies are very diverse ; however initial studies show changes in clinical outcomes , adherence , and health communication , including improved communication with providers , decrease in travel time , ability to receive expert advice , changes in clinical outcomes , and new forms of cost-effective education . While this initial review is promising , more evidence is needed to support and direct system-level re source investment BACKGROUND Type 2 diabetes can often be prevented by lifestyle modification ; however , successful lifestyle intervention programmes are labour intensive . Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification . We aim ed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance . METHODS We did a prospect i ve , parallel-group , r and omised controlled trial between Aug 10 , 2009 , and Nov 30 , 2012 , at ten sites in southeast India . Working Indian men ( aged 35 - 55 years ) with impaired glucose tolerance were r and omly assigned ( 1:1 ) with a computer-generated r and omisation sequence to a mobile phone messaging intervention or st and ard care ( control group ) . Participants in the intervention group received frequent mobile phone messages compared with controls who received st and ard lifestyle modification advice at baseline only . Field staff and participants were , by necessity , not masked to study group assignment , but allocation was concealed from laboratory personnel as well as principal and co-investigators . The primary outcome was incidence of type 2 diabetes , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00819455 . RESULTS We assessed 8741 participants for eligibility . 537 patients were r and omly assigned to either the mobile phone messaging intervention ( n=271 ) or st and ard care ( n=266 ) . The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls : 50 ( 18 % ) participants in the intervention group developed type 2 diabetes compared with 73 ( 27 % ) in the control group ( hazard ratio 0·64 , 95 % CI 0·45 - 0·92 ; p=0·015 ) . The number needed to treat to prevent one case of type 2 diabetes was 11 ( 95 % CI 6 - 55 ) . One patient in the control group died suddenly at the end of the first year . We recorded no other serious adverse events . INTERPRETATION Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk . FUNDING The UK India Education and Research Initiative , the World Diabetes Foundation 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 : Stress among diabetic patients is much more as compared to normal individuals . A delayed recognition of stress undoubtedly worsens the prognosis for survival for many diabetic patients . Hence , this study was planned to develop an intervention model for the reduction of stress among diabetic patients and to evaluate the developed intervention model in the proposed group . Methods : This study was conducted in endocrinology outpatient department of a tertiary care hospital . Starting at r and om , the patients were allocated to control group and test group . Controls were given printed educational material s. Test group were counseled with intense lifestyle education using both printed material s and computers ; they were contacted by telephones by the investigator every 3 weeks for 3 months and SMS were sent every week containing some educational tips . Results : Mean age was 54 ± 11.5 years overall ranging from 30 years to 80 years . About two-third of participants were males with similar distribution in both the groups ( intervention = 66 % , control = 64 % ) . Half ( 50 % ) of the participants lived in joint families , followed by nuclear families ( 40 % ) . Most ( 83 % ) were married and with either graduate or above graduate education ( n = 39 % ) . No significant difference was observed in socio-demographic characteristics among both control and intervention groups ( P > 0.05 ) . The average stress scores were similar ( 18.9 ) at baseline for control and intervention arms . At 3-month follow-up , however , these scores reduced to 17.05 in the intervention arm while they increased to 20.7 in the control arm . At 3 months follow-up , higher proportion of stress reduction was seen in the intervention group . Conclusions : Intervention in the form of intensive lifestyle education and phone calls and SMS significantly decrease their stress score . Mobile-based education has great potential to improve their mental status and increase patient-provider communication , and to decrease stress Background Given the complex and evolving needs of individuals with multimorbidity , the adoption of mHealth tools to support self-management efforts is increasingly being explored , particularly in primary care setting s. The electronic patient-reported outcomes ( ePRO ) tool was codeveloped with patients and providers in an interdisciplinary primary care team in Toronto , Canada , to help facilitate self-management in community-dwelling adults with multiple chronic conditions . Objective The objective of study is to explore the experience and expectations of patients with multimorbidity and their providers around the use of the ePRO tool in supporting self-management efforts . Methods We conducted a 4-week pilot study of the ePRO tool . Patients ’ and providers ’ experiences and expectations were explored through focus groups that were conducted at the end of the study . In addition , thematic analyses were used to assess the shared and contrasting perspectives of patients and providers on the role of the ePRO tool in facilitating self-management . Coded data were then mapped onto the Individual and Family Self-Management Theory using the framework method . Results In this pilot study , 12 patients and 6 providers participated . Both patients and providers emphasized the need for a more explicit recognition of self-management context , including greater customizability of content to better adapt to the complexity and fluidity of self-management in this particular patient population . Patients and providers highlighted gaps in the extent to which the tool enables self-management processes , including how limited progress toward self-management goals and the absence of direct provider engagement through the ePRO tool inhibited patients from meeting their self-management goals . Providers highlighted proximal outcomes based on their experience of the tool and specifically , they indicated that the tool offered valuable insights into the broader patient context , which helps to inform the self-management approach and activities they recommend to patients , whereas patients recognized the tool ’s potential in helping to improve access to different providers in a team-based primary care setting . Conclusions This study identifies a more explicit recognition of the context ual factors that influence patients ’ ability to self-manage and greater adaptability to accommo date patient complexity and provider workflow as next steps in refining the ePRO tool to better support self-management efforts in primary care ahead of its application in a full-scale r and omized pragmatic trial Limited availability of r and omized control trial warranted the conduct of a present study to demonstrate the effectiveness of mobile phone-based short message services ( SMSs ) on reduction in mean fasting blood glucose ( FBG ) in patients with type-2 diabetes mellitus . A total of 955 patients were recruited from primary and secondary health-care facilities and r and omized to intervention ( 479 ) and control ( 476 ) group . Messages were delivered to patients for 12 months tailoring to their recent FBG values . SMS included information to maintain the desired FBG levels and next due date for FBG assessment . Patients were statistically similar for their age , socioeconomic status , smoking , and alcohol use . After the intervention , an average FBG declined from 163.7 to 152.8 mg/dl ( P = 0.019 ) in intervention and from 150.5 to 149.2 mg/dl ( P = 0.859 ) in control group . Adjusted for the baseline FBG , the intervention was found to be significantly effective ( odds ratio : 1.7 ; 95 confidence interval : 1.2–2.6 ) Introduction : Medication nonadherence is the most common issue observed in the management of diabetes because of complex and lifelong therapy . The study aim ed to assess the effect of pharmacist-directed counseling and daily text message reminder on medication adherence and clinical profile of patients with type II diabetes . Material s and Methods : This prospect i ve , open-labeled , r and omized control trial was carried out in outpatient medical department of a secondary care referral hospital . A total of 330 patients who met study criteria were enrolled and r and omized into an intervention group ( n = 165 ) , received counseling and daily messages about medication intake and control group ( n = 165 ) , and usual care by physician . Medication adherence and clinical outcomes such as glycosylated hemoglobin ( HbA1C ) , systolic blood pressure ( SBP ) , low-density lipoprotein ( LDL ) cholesterol , triglyceride ( TG ) levels , and body mass index ( BMI ) were recorded at baseline and follow-up visits . Two- sample Wilcoxon rank sum test was used to compare the mean difference of medication adherence and paired t-test was used to compare clinical outcomes . Results and Discussion : The mean age of intervention and control groups were 57.1±8.55 and 58.5±8.53 years , respectively . The mean difference of medication adherence from baseline to second follow-up visit was significantly more in intervention group ( 12.2±7.1 % ) compared to that in control group ( 0.75±10.2 % ) with a P < 0.001 . From baseline to second follow-up visit , HbA1C ( 7.79±0.67 to 6.91±0.83 % ) , SBP ( 136.75±20.09 to 126.23±18.22 mm Hg ) , and LDL cholesterol ( 104.14±26.23 to 98.29±20.87mg/dL ) levels were significantly reduced in intervention group compared to that in control group with a P < 0.01 . No significant improvement was observed in TG ( 169±33.71 to 168 65±33.90mg/dL ) and BMI ( 27.9±4.21 to 27.1±3.12Kg/m2 ) levels from baseline to second follow-up visit . Conclusion : Pharmacist-directed patient counseling combined with message reminder showed a greater effect on the improvement of medication adherence and control of glycemia , blood pressure , and lipid profile in diabetes Introduction Multimorbidity increases care needs and primary care use among people with chronic diseases . The Concerto Health Program ( CHP ) has been developed to optimise chronic disease management in primary care services . However , in its current version , the CHP primarily targets clinicians and does not aim to answer directly patients ’ and their informal caregivers ’ needs for chronic disease management . Various studies have shown that interventions that increase patient activation level are associated with better health outcomes . Furthermore , educational tools must be adapted to patients and caregivers in terms of health literacy and usability . This project aims to develop , implement and evaluate a user-centred , multifunctional and personalised eHealth platform ( CONCERTO+ ) to promote a more active patient role in chronic disease management and decision-making . Methods and analysis This project uses a collaborative research approach , aim ing at the personalisation of CHP through three phases : ( 1 ) the development of one module of an eHealth platform based on scientific evidence and user-centred design ; ( 2 ) a feasibility study of CONCERTO+ through a pilot cluster r and omised controlled trial where patients with chronic diseases from a primary healthcare practice will receive CONCERTO+ during 6 months and be compared to patients from a control practice receiving usual care and ( 3 ) an analysis of CONCERTO+ potential for scaling up . To do so , we will conduct two focus groups with patients and informal caregivers and individual interviews with health professionals at the two study sites , as well as health care managers , information officers and representatives of the Ministry of Health . Ethics and dissemination This study received ethical approval from Ethics Committee of Université Laval . The findings will be used to inform the effectiveness of CONCERTO+ to improve management care in chronic diseases . We will disseminate findings through presentations in scientific conferences and publication in peer- review ed journals . Trial registration number NCT03628963 ; Pre- results Mobile phone short messaging service ( SMS ) reminders may be a low-cost method for promoting medication adherence . Our objective was to determine whether text SMS reminders improve medication adherence in patients with bipolar I disorder even after discontinuation of the intervention . Participants were stable adult bipolar I disorder out patients on maintenance medication who were r and omized to receive treatment as usual ( TAU ; n = 70 ) or TAU plus twice-weekly medication reminders by SMS ( n = 62 ) for 3 months . Rater-blinded assessment s of medication adherence , treatment attitudes , and quality of life ( QoL ) were obtained at baseline , at the 3-month intervention endpoint , and at a 3-month post-intervention follow up during which both groups received TAU . Intent-to-treat analyses were conducted on the full r and omized sample . The clinical trial protocol was registered with the Clinical Trials Registry of India ( CTRI ) ( CTRI/2016/07/007101 ) . The SMS intervention improved medication adherence and attitudes towards medication at the end of the treatment phase ; these benefits were maintained for medication adherence but not for attitudes towards medication at the end of the follow-up phase . The SMS intervention did not improve QoL outcomes . These findings indicate that biweekly SMS reminders improve medication adherence and the benefits persist for at least 3 months after the SMS reminders are discontinued . The SMS reminders do not affect attitudes towards treatment or |
11,279 | 32,080,785 | This review identified that a number of self-management strategies that were initiated by patients , including heat , exercise , meditation , and transcutaneous electrical nerve stimulation ( TENS ) therapy , may reduce self-reported PN symptoms .
As the available studies were of low quality , these strategies warrant further investigation with more homogeneous sample s , using more rigorously design ed trials and larger sample s. Patients experiencing PN may find a range of self-initiated strategies beneficial in reducing PN symptoms and improving quality of life . | A small number of studies report that patients with peripheral neuropathy ( PN ) who engage in activities that promote a sense of personal well-being and provide physical , emotional , or spiritual comfort have a better quality of life and higher levels of adjustment to the changes generated by their illness and accompanying symptoms .
This systematic review sought to evaluate the effectiveness of self-management activities that patients with PN initiate themselves to relieve PN symptoms and improve quality of life . | Background The introduction of antiretroviral therapy ( ART ) has dramatically reduced the mortality rate of people living with HIV ( PLHIV ) . However , complications of both HIV and ART , such as peripheral neuropathy currently affect PLHIV . The purpose of this study was to establish the prevalence of peripheral neuropathy of the lower extremity and , its association with demographic and health status , characteristics among people on ART in Rw and a. Methods A cross sectional study was conducted among 507 women and men aged between 18 and 60 years , on ART , r and omly selected from eight selected ART clinics in Rw and a. Brief Peripheral Neuropathy Screen was used to assess peripheral neuropathy . Results Peripheral neuropathy prevalence was 59 % overall , mean age of the participants was 39.7 ( ±9.2 ) and a slightly older age was associated with peripheral neuropathy ; [ 42(±9.2 ) vs 37 ( ±8.8 ) ( p < 0.001 ) ] . 78 % of participants living in urban setting s compared to 40 % in rural setting s reported peripheral neuropathy , 69 % of participants with higher levels of education ( secondary level and above ) reported lower extremity neuropathy . The three factors were significantly associated with peripheral neuropathy in multivariable model analysis : older age [ aOR = 1.1 , 95 % CI ( 1.0 , 1.2 ) , p < 0.001 ] , primary education level [ aOR = 0.6 95 % Cl ( 0.3 , 1.0 ) , p = 0.04 ] and urban setting [ aOR = 0.1 , 95 % CI ( 0.06 , 0.3 ) , p < 0.001 ] , after adjusting for other factors . None of the health status characteristics namely ; the level of CD4 cell count , duration of HIV infection and duration on ART , was independently associated with peripheral neuropathy . Conclusions The prevalence of peripheral neuropathy among PLHIV on ART in Rw and a is high . It is unclear why urban setting has an effect on PN levels in this cross sectional study , but does suggest that unidentified social and lifestyles factors may have a role in subjective symptoms and objective signs , of PN Aim To clinical ly evaluate the effectiveness of acupuncture when used in the management of chemotherapy-induced peripheral neuropathy ( PN ) . Background During cancer treatment , certain chemotherapies can cause varying degrees of PN . Patients ’ quality of life can be seriously impaired through loss of sensation , pain or mobility problems . Conventional medications routinely used to manage neuropathic symptoms have poor side-effect profiles and there is little or no evidence justifying their use to treat chemotherapy-related neurotoxicities . There are studies suggesting that acupuncture may be an effective therapy in treating PN across a number of different aetiologies . Design A retrospective service evaluation . Method Patients ( n=18 ) were referred for acupuncture by the medical staff and /ornurse specialists or they self-referred for treatment . A course of six weekly acupuncture sessions was offered to them , and their details were recorded on an evaluation form prior to session one . Points were selected by acupuncturists , based on patient presentation , and needles remained in situ for 30–45 min . Treatments took place in outpatient clinics , chemotherapy day case ward or a drop-in clinic based in a physiotherapy gym . The evaluation form was completed at the end of session 6 by a therapist who had not been involved in patient care . Results 82 % ( n=14 ) of patients reported an improvement in symptoms following their course of acupuncture ; one patient with advanced disease died during the 6 weeks . Some patients derived additional benefits from the treatment including a reduction in analgesic use and improved sleeping patterns . The most common acupoints used were SP6 ( n=18 ) , ST36 ( n=18 ) and LV3 ( n=14 ) . Conclusion Although these results are encouraging , they are uncontrolled . They suggest that acupuncture could be an option for these patients and controlled trials using vali date d patient-reported outcome measures are justified Objective To evaluate the effect of 8-week moderate intensity aerobic ( heart-rate reserve 40–60 % ) exercise on neuropathy quality of life in type 2 diabetes . Methods A single blind , parallel-group , r and omized controlled trial was carried out in a tertiary setting . People with type 2 diabetes were eligible for the study if they had clinical neuropathy which was defined by a minimum score of seven on the Michigan diabetic neuropathy score . Following which , the patients were r and omly assigned to an 8-week program by a computer-generated r and om number tables to intervention or control group . Repeated measure analysis of variance was used for data analysis ( p < 0.05 was considered significant ) . Results There were 47 participants in the control group and 40 participants in the study group after r and omization but 37 from the control group and 29 from the intervention group completed the final analysis . The two groups had a significant difference , pre – post intervention in scores of pain ( F = 7 , p = 0.01 ) , sensory symptoms ( F = 4.60 , p = 0.04 ) , restricted activities of daily living ( F = 4.97 , p = 0.03 ) , disruptions in social relationships ( F = 5.43 , p = 0.02 ) , specific impact on quality of life ( F = 9.28 , p < 0.001 ) overall quality of life ( F = 28.72 , p < 0.001 ) , and total score ( F = 31.10 , p < 0.001 ) . Degrees of freedom for all the components were 1 , 62 . Conclusion Moderate intensity aerobic exercise is cornerstone in improving the quality of life of individuals with peripheral neuropathy in type 2 diabetes OBJECTIVE Labor pain and its management is a major concern for childbearing women , their families and health care providers . This study aim ed to investigate the effects of two non-pharmacological methods such as birth ball and heat therapy on labor pain relief . MATERIAL & METHODS This r and omized control trial was undertaken on 90 primiparous women aged 18 - 35 years old who were r and omly assigned to two intervention ( birth ball and heat ) and control groups . The pain score was recorded by using Visual Analogue Scale ( VAS ) before the intervention and every 30 min in three groups until cervical dilatation reached 8 cm . RESULTS The mean pain severity score in the heat therapy group was less than that of in control group at 60 and 90 min after intervention ( p < 0.05 ) . In addition there were significantly differences between the pain scores in the birth ball group after all three investigated times in comparison to control group . CONCLUSION Both heat therapy and birth ball can use as inexpensive complementary and low risk treatment for labor pain PURPOSE The aim of this study was to determine the effects of Tai Chi exercise on glucose control , neuropathy scores , balance , and quality of life in patients with type 2 diabetes and neuropathy . METHODS A pretest-posttest design with a nonequivalent control group was utilized to recruit 59 diabetic patients with neuropathy from an outpatient clinic of a university hospital . A st and ardized Tai Chi for diabetes program was provided , which comprised 1 hour of Tai Chi per session , twice a week for 12 weeks . Outcome variables were fasting blood glucose and glycosylated hemoglobin for glucose control , the Semmes-Weinstein 10-g monofilament examination scores and total symptom scores for neuropathy , single leg stance for balance , and the Korean version of the SF-36v2 for quality of life . Thirty-nine patients completed the posttest measures after the 12-week Tai Chi intervention , giving a 34 % dropout rate . RESULTS The mean age of the participants was 64 years , and they had been diagnosed with type 2 diabetes for more than 12 years . The status was significantly better for the participants in the Tai Chi group ( n=20 ) than for their control ( i.e. , nonintervention ) counterparts ( n=19 ) in terms of total symptom scores , glucose control , balance , and quality of life . CONCLUSION Tai Chi improved glucose control , balance , neuropathic symptoms , and some dimensions of quality of life in diabetic patients with neuropathy . Further studies with larger sample s and long-term follow-up are needed to confirm the effects of Tai Chi on the management of diabetic neuropathy , which may have an impact on fall prevention in this population [ Purpose ] The aim of this double-blind , r and omized and placebo-controlled study is to investigate the effects of Transcutaneous Electrical Nerve Stimulation for reducing the side effects of Chemotherapy-induced Peripheral Neuropathy in cancer patients undergoing chemotherapy with oxaloplatin or paclitaxel . [ Subjects and Methods ] Twenty-four patients were r and omly allocated into two groups : active or placebo stimulation . All patients were assessed for pain , numbness/tingiling , frequency of symptoms , and quality of life . The transcutaneous Electrical Nerve Stimulation device was applied daily with modulating frequencies ranging between 7 Hz and 65 Hz in distal limb regions during three cycles of chemotherapy ( 45 days ) . The other stimulation parameters were : pulse duration of 200 μsec , intensity at the highest tolerable level , and increases in intensity when it diminished . [ Results ] The data showed no difference between active or placebo groups in terms of pain , numbness/tingling , frequency of symptoms or impact on daily life activities . [ Conclusion ] These results suggest that Transcutaneous Electrical Nerve Stimulation applied in the frequency variation mode was not proven to be effective to improve the symptoms of Chemotherapy-induced Peripheral Neuropathy during chemotherapy cycles . There was no worsening of symptoms in subsequent cycles of the onset of symptoms of the disease OBJECTIVE —The purpose of this study was to determine the efficacy of anodyne monochromatic infrared photo energy ( MIRE ) in-home treatments over a 90-day period to improve peripheral sensation and self-reported quality of life in individuals with diabetes . RESEARCH DESIGN AND METHODS —This was a double-blind , r and omized , sham-controlled clinical trail . We r and omly assigned 69 individuals with diabetes and a vibration perception threshold ( VPT ) between 20 and 45 V to two treatment groups : active or sham treatment . Sixty patients ( 120 limbs ) completed the study . Anodyne units were used at home every day for 40 min for 90 days . We evaluated nerve conduction velocities , VPT , Semmes-Weinstein monofilaments ( SWM ) ( 4- , 10- , 26- , and 60-g monofilaments ) , the Michigan Neuropathy Screening Instrument ( MNSI ) , a 10-cm visual analog pain scale , and a neuropathy-specific quality of life instrument . We used a nested repeated- measures multiple ANOVA design . Two sites ( great toe and fifth metatarsal ) were tested on both the left and right feet of each patient , so two feet were nested within each patient and two sites were nested within each foot . To analyze the ordinal SWM scores , we used a nonparametric factorial analysis for longitudinal data . RESULTS —There were no significant differences in measures for quality of life , MNSI , VPT , SWM , or nerve conduction velocities in active or sham treatment groups ( P > 0.05 ) . CONCLUSIONS —Anodyne MIRE therapy was no more effective than sham therapy in the treatment of sensory neuropathy in individuals with diabetes BACKGROUND AND PURPOSE The effects of a home exercise program for persons with chronic peripheral neuropathies ( CPN ) have not been documented . We compared changes in impairment and health-related quality of life ( HRQL ) between exercise and control groups , investigated the relationship between HRQL and measures of impairment , and contrasted the HRQL of individuals with CPN to that previously described for the general population . SUBJECTS Twenty-eight subjects with CPN , aged 23 to 84 years ( mean = 56.2 , SD = 14.9 ) , completed the study . METHODS Impairment measures included average muscle score ( AMS ) , h and grip force , walking time , and forced vital capacity . The HRQL instrument measured the eight scales of the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the component scales . The exercise group ( n = 14 ) completed a 6-week home exercise program . The control group ( n = 14 ) did not participate in a home exercise program . RESULTS There was an increase in the AMS in the exercise group compared with the control group . No other between-group differences were found . The exercise group improved in scores on the role limitation scales of the SF-36 . The AMS and walking time were moderately correlated with the physical function scale of the SF-36 ( r = .55 and -.62 , respectively ) . The SF-36 scores of individuals with CPN were lower than scores previously described for the general population . CONCLUSION AND DISCUSSION The home exercise program appears to be an important component of the treatment of persons with CPN . Compared with the general population , patients with CPN appear to have a lower HRQL , but some areas appear to improve following a home exercise program Purpose Muscle pain is a natural consequence of intense and prolonged exercise and has been suggested to be a limiter of performance . Transcutaneous electrical nerve stimulation ( TENS ) and interferential current ( IFC ) have been shown to reduce both chronic and acute pain in a variety of conditions . This study sought to ascertain whether TENS and IFC could reduce exercise-induced pain ( EIP ) and whether this would affect exercise performance . It was hypothesised that TENS and IFC would reduce EIP and result in an improved exercise performance . Methods In two parts , 18 ( Part I ) and 22 ( Part II ) healthy male and female participants completed an isometric contraction of the dominant bicep until exhaustion ( Part I ) and a 16.1 km cycling time trial as quickly as they could ( Part II ) whilst receiving TENS , IFC , and a SHAM placebo in a repeated measures , r and omised cross-over , and placebo-controlled design . Perceived EIP was recorded in both tasks using a vali date d subjective scale . Results In Part I , TENS significantly reduced perceived EIP ( mean reduction of 12 % ) during the isometric contraction ( P = 0.006 ) and significantly improved participants ’ time to exhaustion by a mean of 38 % ( P = 0.02 ) . In Part II , TENS significantly improved ( P = 0.003 ) participants ’ time trial completion time ( ~2 % improvement ) through an increased mean power output . Conclusion These findings demonstrate that TENS can attenuate perceived EIP in a healthy population and that doing so significantly improves endurance performance in both submaximal isometric single limb exercise and whole-body dynamic exercise Chemotherapy-induced peripheral neuropathy ( CIPN ) is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered . Acupuncture may be effective for treating peripheral neuropathy . The aim of this study was to review the available literature on the use of acupuncture for CIPN . The systematic literature search was performed using MEDLINE , Google Scholar , Cochrane Data base , CINHAL , and ISI Proceedings . H and search ing was conducted , and consensus was reached on all extracted data . Only papers in the English language were included , irrespective of study design . From 3989 retrieved papers , 8 relevant papers were identified . One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats . In addition , there were 7 very heterogeneous clinical studies , 1 controlled r and omised study using auricular acupuncture , 2 r and omized controlled studies using somatic acupuncture , and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN . Conclusions . Only one controlled r and omised study demonstrated that acupuncture may be beneficial for CIPN . All the clinical studies review ed had important method ological limitations . Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN result ing from cancer treatment Purpose Chemotherapy-induced peripheral neuropathy ( CIPN ) is increasing with introduction of new and combination cancer pharmacotherapies . This study evaluated associations between clinical and self-report measurements and current perception threshold ( CPT ) , a neuroselective measure of sensory nerve function that may detect asymptomatic CIPN damage . Methods Data for this secondary analysis were from a prospect i ve , observational study using CPT to evaluate CIPN . Bivariate mixed models , accounting for the intraclass correlation between repeated patient assessment s , were used to assess the relationship between CPT at each frequency ( 5 , 250 , and 2,000 Hz ) and each subjective measure ( Neuropathic Pain Scale , FACT-GOGntx ) and objective measurement ( quantitative sensory testing , deep tendon reflexes , and grip strength ) . Results A total of 29 chemotherapy-naïve subjects with various cancer types had a mean age of 56.7 ( SD 10.4 ) ; nine subjects developed CIPN grade > 1 using NCI CTC-AE criteria . Cold detection thresholds were inversely associated with CPT 5 [ b(95 % CI ) = −2.5(−4.5 , −0.5 ) ] and CPT 2,000 [ −7.5(−11.8 , −3.3 ) ] frequencies . FACT GOG-ntx quality of life ( QoL ) scale and neurotoxicity and function subscales were inversely associated with CPT 2,000 [ −1.8 ( −3.5 , −0.05 ) , −2.2 ( −4.2 , −0.2 ) , and −5.4 ( −9.8 , −0.9 ) , respectively ] , indicating worsening QoL , impairment , and function as hypoesthesia increases . Conclusions CPT 2,000 may identify impending worsening of patient-reported outcomes such as Aims /hypothesisDiabetic distal symmetrical sensory polyneuropathy ( DSP ) affects 20–30 % of diabetic patients . Transcutaneous electrical nerve stimulation ( TENS ) and electrical spinal cord stimulation have been proposed as physical therapies . We performed a controlled , r and omised pilot trial to compare the effects of high-frequency external muscle stimulation ( HF ) with those of TENS in patients with symptomatic DSP . Methods Patients with type 2 diabetes and DSP ( n=41 ) were r and omised to receive treatment with TENS or HF using strata for non-painful ( n=20 ) and painful sensory symptoms ( n=21 ) . Both lower extremities were treated for 30 min daily for three consecutive days . The patients ’ degree of symptoms and pain were grade d daily on a scale of one to ten , before , during and 2 days after treatment termination . Responders were defined by the alleviation of one or more symptoms by at least three points . Results The two treatment groups were similar in terms of baseline characteristics , such as age , duration of diabetes , neurological symptoms scores and neurological disability scores . The responder rate was significantly higher ( p<0.05 ) in the HF group ( 80 % , 16 out of 20 ) than in the TENS group ( 33 % , seven out of 21 ) . Subgroup analysis revealed that HF was more effective than TENS in relieving the symptoms of non-painful neuropathy ( HF : 100 % , seven out of seven ; TENS : 44 % , four out of nine ; p<0.05 ) and painful neuropathy ( HF : 69 % , nine out of 13 ; TENS : 25 % , three out of 12 ; p<0.05 ) . The responders did not differ in terms of the reduction in mean symptom intensity during the trial . Conclusions /interpretationThis pilot study shows , for the first time , that HF can ameliorate the discomfort and pain associated with DSP , and suggests that HF is more effective than TENS . External muscle stimulation offers a new therapeutic option for DSP OBJECTIVE To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Thirty-one patients with symptoms and signs of peripheral neuropathy were r and omized to the electrotherapy or sham treatment ( control ) group . The electrostimulation was given by a portable unit ( H-Wave machine ) than generated a biphasic , exponentially decaying waveform ( pulse width 4 ms , 25–35 V , ≥ 2 Hz ) . Patients treated each of their lower extremities for 30 min daily for 4 weeks at home . Nine patients from the sham-treatment group participated for a second period , during which all of them received the active electrotherapy . Patient 's degree of pain and discomfort was grade d on a scale of 0 to 5 . RESULTS In the sham-treated group ( n = 13 ) , the neuropathic symptoms improved in five ( 38 % ) patients , and the pain score declined from 2.92 ± 0.13 to 2.38 ± 0.26 ( P < 0.04 ) , suggesting a procedure-related placebo effect . In the electrotherapy group ( n = 18 ) , symptomatic improvement was seen in 15 ( 83 % ) cases , 3 of which were completely asymptomatic ; the pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 ( P < 0.01 ) and the posttreatment pain scores were considerably lower ( P < 0.03 ) , indicating a substantial treatment effect over and above any placebo influence . Patients in the electrotherapy group reported greater reduction in symptoms ( 52 ± 7 % vs. 27 ± 10 % in control subjects , P < 0.05 ) on an analog scale . Moreover , the electrotherapy decreased pain scores ( from 3.0 ± 0.62 to 1.56 ± 0.32 , P < 0.02 ) in nine patients who had received sham treatment earlier . CONCLUSIONS A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy . This novel modality offers a potential non-pharmacological treatment option Background Chemotherapy-induced peripheral neuropathy ( CIPN ) is a troublesome chronic symptom that has no proven pharmacologic treatment . The purpose of this double-blind r and omized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem . Methods Patients with CIPN were r and omized to baclofen 10 mg , amitriptyline HCL 40 mg , and ketamine 20 mg in a pluronic lecithin organogel ( BAK-PLO ) versus placebo ( PLO ) to determine its effect on numbness , tingling , pain , and function . The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20 , at 4 weeks . Results Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory ( p = 0.053 ) and motor subscales ( p = 0.021 ) . The greatest improvements were related to the symptoms of tingling , cramping , and shooting/burning pain in the h and s as well as difficulty in holding a pen . There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity . Conclusion Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN . This topical gel was well tolerated , without evident systemic toxicity . Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN CONTEXT For patients with chronic disease , there is growing interest in " self-management " programs that emphasize the patients ' central role in managing their illness . A recent r and omized clinical trial demonstrated the potential of self-management to improve health status and reduce health care utilization in patients with chronic diseases . OBJECTIVE To evaluate outcomes of a chronic disease self-management program in a real-world " setting . STUDY DESIGN Before-after cohort study . PATIENTS AND SETTING Of the 613 patients from various Kaiser Permanente hospitals and clinics recruited for the study , 489 had complete baseline and follow-up data . INTERVENTION The Chronic Disease Self-Management Program is a 7-week , small-group intervention attended by people with different chronic conditions . It is taught largely by peer instructors from a highly structured manual . The program is based on self-efficacy theory and emphasizes problem solving , decision making , and confidence building . MAIN OUTCOME MEASURES Health behavior , self-efficacy ( confidence in ability to deal with health problems ) , health status , and health care utilization , assessed at baseline and at 12 months by self-administered question naires . RESULTS At 1 year , participants in the program experienced statistically significant improvements in health behaviors ( exercise , cognitive symptom management , and communication with physicians ) , self-efficacy , and health status ( fatigue , shortness of breath , pain , role function , depression , and health distress ) and had fewer visits to the emergency department ( ED ) ( 0.4 visits in the 6 months prior to baseline , compared with 0.3 in the 6 months prior to follow-up ; P = 0.05 ) . There were slightly fewer outpatient visits to physicians and fewer days in hospital , but the differences were not statistically significant . Results were of about the same magnitude as those observed in a previous r and omized , controlled trial . Program costs were estimated to be about $ 200 per participant . CONCLUSIONS We replicated the results of our previous clinical trial of a chronic disease self-management program in a " real-world " setting . One year after exposure to the program , most patients experienced statistically significant improvements in a variety of health outcomes and had fewer ED visits AIMS AND OBJECTIVES To investigate the effects of local heat therapy on chest pain in patients with acute coronary syndrome . BACKGROUND Chest pain is a very common complaint in patients with acute coronary syndrome . It is managed both pharmacologically and nonpharmacologically . Pharmacological pain management is associated with different side effects . DESIGN This was a r and omised double-blind placebo-controlled clinical trial conducted in 2013 . METHODS A convenience sample of 66 patients with acute coronary syndrome was selected from a coronary care unit of a local teaching hospital affiliated to Gonabad University of Medical Sciences , Gonabad , Iran . Patients were r and omly assigned to either the experimental or the placebo group . Patients in the experimental and the placebo groups received local heat therapy using a hot pack warmed to 50 and 37 ° C , respectively . We assessed chest pain intensity , duration and frequency as well as the need for opioid analgesic therapy both before and after the study . The study instrument consisted of a demographic question naire , the McGill Pain Question naire , and a data sheet for documenting pain frequency and duration as well as the need for analgesic therapy . FINDINGS The placebo heat therapy did not significantly decrease the intensity , the duration and the frequency of pain episodes . However , pain intensity , duration and frequency in the experimental group decreased significantly after the study . Moreover , the groups differed significantly in terms of the need for opioid analgesic therapy neither before nor after the intervention . CONCLUSION Local heat therapy is an effective intervention for preventing and relieving chest pain in patients with acute coronary syndrome . RELEVANCE TO CLINICAL PRACTICE Effective pain management using local heat therapy could help nurses play an important role in providing effective care to patients with acute coronary syndrome and in minimising adverse effects associated with pain medications UNLABELLED Although exercise can significantly reduce the prevalence and severity of diabetic complications , no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy ( DPN ) . The purpose of this pilot study was to examine feasibility and effectiveness of a supervised , moderately intense aerobic and resistance exercise program in people with DPN . We hypothesized that the exercise intervention can improve neuropathic symptoms , nerve function , and cutaneous innervation . METHODS A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program . Seventeen subjects with diagnosed DPN ( 8 males/9 females ; age 58.4±5.98 ; duration of diabetes 12.4±12.2 years ) completed the study . Outcome measures included pain measures ( visual analog scale ) , Michigan Neuropathy Screening Instrument ( MNSI ) question naire of neuropathic symptoms , nerve function measures , and intraepidermal nerve fiber ( IENF ) density and branching in distal and proximal lower extremity skin biopsies . RESULTS Significant reductions in pain ( -18.1±35.5 mm on a 100 mm scale , P=.05 ) , neuropathic symptoms ( -1.24±1.8 on MNSI , P=.01 ) , and increased intraepidermal nerve fiber branching ( + 0.11±0.15 branch nodes/fiber , P=.008 ) from a proximal skin biopsy were noted following the intervention . CONCLUSIONS This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy . These findings are particularly promising given the short duration of the intervention , but need to be vali date d by comparison with a control group in future studies IN BRIEF Painful diabetic peripheral neuropathy ( PDPN ) has a large negative impact on patients ’ physical and mental functioning , and pharmacological therapies rarely provide more than partial relief . Mindfulness-based stress reduction ( MBSR ) is a group psychosocial intervention that was developed for patients with chronic illness who were not responding to existing medical treatments . This study tested the effects of community-based MBSR courses for patients with PDPN . Among patients whose PDPN pharmacotherapy had been optimized in a chronic pain clinic , those r and omly assigned to treatment with MBSR experienced improved function , better health-related quality of life , and reduced pain intensity , pain catastrophizing , and depression compared to those receiving usual care In a double blind , r and omised study , 19 patients suffering from mild-to-moderate symptomatic diabetic neuropathy ( Total Symptom Score , NTSS 4 - 16 ) received either treatment with the new transcutaneous electrical nerve stimulation ( TENS ) device " Salutaris " ( verum group ) or a placebo treatment with an identical but electrically inactive device ( placebo group ) . Stimulation pads were placed at the anatomical localisation of the peroneal nerve and stimulation was performed using a low frequency mode . At baseline ( V1 ) , after 6 ( V2 ) , and 12 ( V3 ) wk of treatment , the patients ' symptoms were registered using the new total symptom score ( NTSS-6 ) and a visual analogue scale ( VAS ) . In addition , sensory nerve thresholds ( temperature , vibration , pain ) and microvascular function were measured at the lower limb at baseline and after 12 wk of treatment . Active TENS-treatment result ed in a significant improvement in NTSS-6 score after 6 wk ( -42 % ) and after 12 wk ( -32 % ) of treatment ( baseline : 10.0+/-3.3 , 6 wk : 5.8+/-5.0 , p<0.05 ; 12 wk : 6.8+/-3.9 , p=0.05 ; placebo group : baseline : 7.6+/-3.1 ; 6 wk : 8.1+/-5.1 , n.s . ; 12 wk : 6.5+/-6.1 , n.s . ) . Sub analysis of the different qualities of the NTSS-score revealed an improvement in numbness ( 2.2+/-1.0 to 1.6+/-1.3 ; p<0.03 ) ; lancinating pain ( 1.6+/-1.1 to 0.6+/-0.9 ; p<0.02 ) and allodynia ( 1.4+/-1.6 to 0.5+/-1.0 ; p<0.05 ) . Also , a significant improvement in the VAS rating was found after 6 wk of TENS therapy ( 19.8+/-5.0 to 14.4+/-9.6 ; p<0.05 ) , while no change was observed in the placebo arm . In conclusion , our study indicates that the new TENS device " Salutaris " is a convenient , non-pharmacological option for primary or adjuvant treatment of painful diabetic neuropathy As part of a larger r and omized controlled trial examining the efficacy of an HIV/AIDS symptom management manual ( n = 775 ) , this study examined the prevalence of peripheral neuropathy in HIV-infected individuals at 12 sites in the USA , Puerto Rico , and Africa . Neuropathy was reported by 44 % of the sample ; however , only 29.4 % reported initiating self-care behaviors to address the neuropathy symptoms . Antiretroviral therapy was found to increase the frequency of neuropathy symptoms , with an increased mean intensity of 28 % . A principal axis factor analysis with Promax rotation was used to assess the relationships in the frequency of use of the 18 self-care activities for neuropathy , revealing three distinct factors : ( i ) an interactive self-care factor ; ( ii ) a complementary medicine factor ; and ( iii ) a third factor consisting of the negative health items of smoking , alcohol , and street drugs . The study 's results suggest that peripheral neuropathy is a common symptom and the presence of neuropathy is associated with self-care behaviors to ameliorate HIV symptoms . The implication s for nursing practice include the assessment and evaluation of nursing interventions related to management strategies for neuropathy Chemotherapy-induced peripheral neuropathy ( CIPN ) occurs in approximately 68 % of patients who receive neurotoxic chemotherapy and lasts at least 6 months post-chemotherapy in approximately 30 % of individuals . CIPN is associated with decreased quality of life and functional impairments . Evidence suggests that CIPN symptoms are caused , in part , by enhanced excitability and impaired inhibition in the central nervous system . Transcutaneous electrical nerve stimulation ( TENS ) decreases pain by counteracting both of these mechanisms and is efficacious in other conditions associated with neuropathic pain . This single-arm study ( n = 29 ) assessed the feasibility of investigating TENS for CIPN after chemotherapy completion using a wireless , home-based TENS device . Eighty-one percent of eligible patients who were approached enrolled , and 85 % of participants who received the TENS device completed the primary ( 6-week ) study term . Qualitative interview data suggest that use of the device on the continuous setting that automatically alternates between 1-h stimulation and rest periods for 5 h/day would be acceptable to most participants . Significant ( i.e. , p < 0.05 ) improvements were observed with the EORTC-CIPN20 ( percent change from baseline : 13 % ) , SF-MPQ-2 ( 52 % ) , numeric rating scale of pain ( 38 % ) , tingling ( 30 % ) , numbness ( 20 % ) , and cramping ( 53 % ) , and UENS large fiber sensation subscore ( 48 % ) . Preliminary data that support the reliability and construct validity of the UENS for CIPN in cancer survivors are also provided . Together these data suggest that it is feasible to evaluate TENS for CIPN using a wireless , home-based device and that further evaluation of TENS for CIPN in a r and omized clinical trial is warranted Purpose Chemotherapy-induced peripheral neuropathy ( CIPN ) affects up to 40 % of cancer survivors and is associated with functional deficits and an increased falls incidence . There are presently no strongly recommended treatment strategies for CIPN . The aim of this study was to evaluate the impact of a multimodal exercise intervention on CIPN symptoms and related functional deficits , as well as neurophysiologic parameters . Methods All outcomes were assessed before and after an 8-week exercise intervention ( 3-weekly sessions ) and preceding 8-week control period at baseline , pre-exercise and post-exercise . Outcome measures were objective and patient-reported CIPN , st and ing and dynamic balance , mobility , quality of life , and sensory and motor nerve excitability and conduction studies . Results Twenty-nine cancer survivors ( 8 male , 21 female ; mean age 61.6 ± 11.8 years ) with CIPN symptoms affecting function completed all assessment s. Objective and patient-reported CIPN , dynamic balance , st and ing balance in eyes open conditions , mobility and quality of life were improved from pre- to post-exercise ( 4.0 < F < 10.2 ; p < .05 ) , with no changes over the control period ( p > .21 ) . No changes were observed in sensory or motor neurophysiologic parameters ( p > .23 ) . Conclusions This study provides encouraging evidence of the rehabilitative potential of multimodal exercise for persisting CIPN in a post-treatment cohort . Large r and omised controlled trials are justified to confirm observed benefits and determine the mechanisms and clinical significance |
11,280 | 32,346,636 | Conclusion The results are not strong enough to develop breast cancer risk in the setting of Asian countries . | Introduction Currently , the Breast Cancer Risk Assessment Tool ( BCRAT ) , also known as the Gail model ( GM ) has been widely recognized and adapted for to study disparity in racial and ethnic groups in America including Asian and Pacific Isl and er American females .
However , its applicability outside America remains uncertain due to diversity in epidemiology and risk factors of breast cancer in population s especially in Asian females .
We sought to evaluate the performance of the GM to predict breast cancer risk in Asian countries . | Introduction The Predicting Risk of Cancer at Screening study in Manchester , UK , is a prospect i ve study of breast cancer risk estimation . It was design ed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model ( Breast Cancer Risk Assessment Tool ) or the Tyrer-Cuzick model ( International Breast Intervention Study model ) . Methods Mammographic density was measured at entry as a percentage visual assessment , adjusted for age and body mass index . Tyrer-Cuzick and Gail 10-year risks were based on a question naire completed contemporaneously . Breast cancers were identified at the entry screen or shortly thereafter . The contribution of density to risk models was assessed using odds ratios ( ORs ) with profile likelihood confidence intervals ( CIs ) and area under the receiver operating characteristic curve ( AUC ) . The calibration of predicted ORs was estimated as a percentage [ ( observed vs expected ( O/E ) ] from logistic regression . Results The analysis included 50,628 women aged 47–73 years who were recruited between October 2009 and September 2013 . Of these , 697 had breast cancer diagnosed after enrolment . Median follow-up was 3.2 years . Breast density [ interquartile range odds ratio ( IQR-OR ) 1.48 , 95 % CI 1.34–1.63 , AUC 0.59 ] was a slightly stronger univariate risk factor than the Tyrer-Cuzick model [ IQR-OR 1.36 ( 95 % CI 1.25–1.48 ) , O/E 60 % ( 95 % CI 44–74 ) , AUC 0.57 ] or the Gail model [ IQR-OR 1.22 ( 95 % CI 1.12–1.33 ) , O/E 46 % ( 95 % CI 26–65 % ) , AUC 0.55 ] . It continued to add information after allowing for Tyrer-Cuzick [ IQR-OR 1.47 ( 95 % CI 1.33–1.62 ) , combined AUC 0.61 ] or Gail [ IQR-OR 1.45 ( 95 % CI 1.32–1.60 ) , combined AUC 0.59 ] . Conclusions Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model PURPOSE To estimate the effects of a tablet-based , breast cancer risk education intervention for use in primary care setting s ( BreastCARE ) on patients ' breast cancer knowledge , risk perception and concern . METHODS From June 2011-August 2012 , we enrolled women from two clinics , aged 40 - 74 years with no personal breast cancer history , and r and omized them to the BreastCARE intervention group or to the control group . All patients completed a baseline telephone survey and risk assessment ( via telephone for controls , via tablet computer in clinic waiting room prior to visit for intervention ) . All women were categorized as high or average risk based on the Referral Screening Tool , the Gail model or the Breast Cancer Surveillance Consortium model . Intervention patients and their physicians received an individualized risk report to discuss during the visit . All women completed a follow-up telephone survey 1 - 2 weeks after risk assessment . Post-test comparisons estimated differences at follow-up in breast cancer knowledge , risk perception and concern . RESULTS 580 intervention and 655 control women completed follow-up interviews . Mean age was 56 years ( SD = 9 ) . At follow-up , 73 % of controls and 71 % of intervention women correctly perceived their breast cancer risk and 22 % of controls and 24 % of intervention women were very concerned about breast cancer . Intervention patients had greater knowledge ( ≥75 % correct answers ) of breast cancer risk factors at follow-up ( 24 % vs. 16 % ; p = 0.002 ) . In multivariable analysis , there were no differences in correct risk perception or concern , but intervention patients had greater knowledge ( [ OR ] = 1.62 ; 95 % [ CI ] = 1.19 - 2.23 ) . CONCLUSIONS A simple , practical intervention involving physicians at the point of care can improve knowledge of breast cancer without increasing concern . TRIAL REGISTRATION Clinical Trials.gov identifier NCT01830933 Introduction Clinicians use different breast cancer risk models for patients considered at average and above-average risk , based largely on their family histories and genetic factors . We used longitudinal cohort data from women whose breast cancer risks span the full spectrum to determine the genetic and nongenetic covariates that differentiate the performance of two commonly used models that include nongenetic factors - BCRAT , also called Gail model , generally used for patients with average risk and IBIS , also called Tyrer Cuzick model , generally used for patients with above-average risk . Methods We evaluated the performance of the BCRAT and IBIS models as currently applied in clinical setting s for 10-year absolute risk of breast cancer , using prospect i ve data from 1,857 women over a mean follow-up length of 8.1 years , of whom 83 developed cancer . This cohort spans the continuum of breast cancer risk , with some subjects at lower than average population risk . Therefore , the wide variation in individual risk makes it an interesting population to examine model performance across subgroups of women . For model calibration , we divided the cohort into quartiles of model-assigned risk and compared differences between assigned and observed risks using the Hosmer-Lemeshow ( HL ) chi-squared statistic . For model discrimination , we computed the area under the receiver operator curve ( AUC ) and the case risk percentiles ( CRPs ) . Results The 10-year risks assigned by BCRAT and IBIS differed ( range of difference 0.001 to 79.5 ) . The mean BCRAT- and IBIS-assigned risks of 3.18 % and 5.49 % , respectively , were lower than the cohort 's 10-year cumulative probability of developing breast cancer ( 6.25 % ; 95 % confidence interval ( CI ) = 5.0 to 7.8 % ) . Agreement between assigned and observed risks was better for IBIS ( HL X42 = 7.2 , P value 0.13 ) than BCRAT ( HL X42 = 22.0 , P value < 0.001 ) . The IBIS model also showed better discrimination ( AUC = 69.5 % , CI = 63.8 % to 75.2 % ) than did the BCRAT model ( AUC = 63.2 % , CI = 57.6 % to 68.9 % ) . In almost all covariate-specific subgroups , BCRAT mean risks were significantly lower than the observed risks , while IBIS risks showed generally good agreement with observed risks , even in the subgroups of women considered at average risk ( for example , no family history of breast cancer , BRCA1/2 mutation negative ) . Conclusions Models developed using extended family history and genetic data , such as the IBIS model , also perform well in women considered at average risk ( for example , no family history of breast cancer , BRCA1/2 mutation negative ) . Extending such models to include additional nongenetic information may improve performance in women across the breast cancer risk continuum Patients can benefit from accessible breast cancer risk information . The Gail model is a well-known means of providing risk information to patients and for guiding clinical decisions . Risk presentation often includes 5-year and lifetime percent chances for a woman to develop breast cancer . How do women perceive their risks after Gail model risk assessment ? This exploratory study used a r and omized clinical trial design to address this question among women not previously selected for breast cancer risk . Results suggest a brief risk assessment intervention changes quantitative and comparative risk perceptions and improves accuracy . This study improves our underst and ing of risk perceptions by evaluating an intervention in a population not previously selected for high-risk status and measuring perceptions in a variety of formats Purpose The Gail model is one of the most widely used tools to assess the risk of breast cancer . However , it is known to overestimate breast cancer risk for Asian women . Here , we vali date the Gail model and the Korean model using Korean data , and subsequently up date and revali date the Korean model using recent data . Methods We vali date d the modified Gail model ( model 2 ) , Asian American Gail model , and a previous Korean model using screening patient data collected between January 1999 and July 2004 . The occurrence of breast cancer was confirmed by matching the resident registration number with data from the Korean Breast Cancer Registration Program . The expected-to-observed ( E/O ) ratio was used to vali date the reliability of the program , and receiver operating characteristics curve analysis was used to evaluate the program 's discriminatory power . There has been a rapid increase in the incidence of breast cancer in Korea , and we up date d and revali date d the Korean model using incidence and mortality rate data from recent years . Results Among 40,229 patients who were included in the validation , 161 patients were confirmed to have developed breast cancer within 5 years of screening . The E/O ratios and 95 % confidence intervals ( CI ) were 2.46 ( 2.10 - 2.87 ) for the modified Gail model and 1.29 ( 1.11 - 1.51 ) for the Asian American Gail model . The E/O ratio and 95 % CI for the Korean model was 0.50 ( 0.43 - 0.59 ) . For the up date d Korean model , the E/O ratio and 95 % CI were 0.85 ( 0.73 - 1.00 ) . In the discriminatory power , the area under curve and 95 % CI of the modified Gail model , Asian American Gail model , Korean model and up date d Korean model were 0.547 ( 0.500 - 0.594 ) , 0.543 ( 0.495 - 0.590 ) , 0.509 ( 0.463 - 0.556 ) , and 0.558 ( 0.511 - 0.605 ) , respectively . Conclusion The up date d Korean model shows a better performance than the other three models . It is hoped that this study can provide the basis for a clinical risk assessment program and a future prospect i ve study of breast cancer prevention Introduction The Gail model ( GM ) is a risk- assessment model used in individual estimation of the absolute risk of invasive breast cancer , and has been applied to both clinical counselling and breast cancer prevention studies . Although the GM has been vali date d in several Western studies , its applicability outside North America and Europe remains uncertain . The Singapore Breast Cancer Screening Project ( SBCSP ) is a nation-wide prospect i ve trial of screening mammography conducted between Oct 1994 and Feb 1997 , and is the only such trial conducted outside North America and Europe to date . With the long-term outcomes from this study , we sought to evaluate the performance of GM in prediction of individual breast cancer risk in a Asian developed country . Methods The study population consisted of 28,104 women aged 50 to 64 years who participated in the SBSCP and did not have breast cancer detected during screening . The national cancer registry was used to identify incident cases of breast cancer . To evaluate the performance of the GM , we compared the expected number of invasive breast cancer cases predicted by the model to the actual number of cases observed within 5-year and 10-year follow-up . Pearson 's Chi-square test was used to test the goodness of fit between the expected and observed cases of invasive breast cancers . Results The ratio of expected to observed number of invasive breast cancer cases within 5 years from screening was 2.51 ( 95 % confidence interval 2.14 - 2.96 ) . The GM over-estimated breast cancer risk across all age groups , with the discrepancy being highest among older women aged 60 - 64 years ( E/O = 3.53 , 95 % CI = 2.57 - 4.85 ) . The model also over-estimated risk for the upper 80 % of women with highest predicted risk . The overall E/O ratio for the 10-year predicted breast cancer risk was 1.85 ( 1.68 - 2.04 ) . Conclusions The GM over-predicts the risk of invasive breast cancer in the setting of a developed Asian country as demonstrated in a large prospect i ve trial , with the largest difference seen in older women aged between 60 and 64 years old . The reason for the discrepancy is likely to be multifactorial , including a truly lower prevalence of breast cancer , as well as lower mammographic screening prevalence locally To vali date an established breast cancer incidence model in an independent prospect i ve data set . After aligning time periods for follow-up , we restricted population s to comparable age ranges ( 47–74 years ) , and followed them for incident invasive breast cancer ( follow-up 1994–2008 , Nurses ’ Health Study [ NHS ] ; and 1995–2009 , California Teachers Study [ CTS ] ) . We identified 2026 cases during 540,617 person years of follow-up in NHS , and 1,400 cases during 288,111 person years in CTS . We fit the Rosner – Colditz log-incidence model and the Gail model using baseline data . We imputed future use of hormones based on type and prior duration of use and other covariates . We assessed performance using area under the curve ( AUC ) and calibration methods . Participants in the CTS had fewer children , were leaner , consumed more alcohol , and were more frequent users of postmenopausal hormones . Incidence rate ratios for breast cancer showed significantly higher breast cancer in the CTS ( IRR = 1.32 , 95 % CI 1.24–1.42 ) . Parameters for the log-incidence model were comparable across the two cohorts . Overall , the NHS model performed equally well when applied in the CTS . In the NHS the AUC was 0.60 ( s.e . 0.006 ) and applying the NHS betas to the CTS the performance in the independent data set ( validation ) was 0.586 ( s.e . 0.009 ) . The Gail model gave values of 0.547 ( s.e . 0.008 ) , a significant 4 % lower , p < 0.0001 . For women 47–69 the AUC values for the log-incidence model are 0.608 in NHS and 0.609 in CTS ; and for Gail are 0.569 and 0.572 . In both cohorts , performance of both models dropped off in older women 70–87 , and later in follow-up ( 6–12 years ) . Calibration showed good estimation against SEER with a non-significant 4 % underestimate of overall breast cancer incidence when applying the model in the CTS population ( p = 0.098 ) . The Rosner – Colditz model performs consistently well when applied in an independent data set . Performance is stronger predicting incidence among women 47–69 and over a 5-year time interval . AUC values exceed those for Gail by 3–5 % based on AUC when both are applied to the independent validation data set . Models may be further improved with addition of breast density or other markers of risk beyond the current model BACKGROUND Initial findings from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial ( P-1 ) demonstrated that tamoxifen reduced the risk of estrogen receptor-positive tumors and osteoporotic fractures in women at increased risk for breast cancer . Side effects of varying clinical significance were observed . The trial was unblinded because of the positive results , and follow-up continued . This report up date s our initial findings . METHODS Women ( n = 13,388 ) were r and omly assigned to receive placebo or tamoxifen for 5 years . Rates of breast cancer and other events were compared by the use of risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) . Estimates of the net benefit from 5 years of tamoxifen therapy were compared by age , race , and categories of predicted breast cancer risk . Statistical tests were two-sided . RESULTS After 7 years of follow-up , the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group ( RR = 0.57 , 95 % CI = 0.46 to 0.70 ) and the cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women in the placebo group to 10.2 per 1000 women in the tamoxifen group ( RR = 0.63 , 95 % CI = 0.45 to 0.89 ) . These reductions were similar to those seen in the initial report . Tamoxifen led to a 32 % reduction in osteoporotic fractures ( RR = 0.68 , 95 % CI = 0.51 to 0.92 ) . Relative risks of stroke , deep-vein thrombosis , and cataracts ( which increased with tamoxifen ) and of ischemic heart disease and death ( which were not changed with tamoxifen ) were also similar to those initially reported . Risks of pulmonary embolism were approximately 11 % lower than in the original report , and risks of endometrial cancer were about 29 % higher , but these differences were not statistically significant . The net benefit achieved with tamoxifen varied according to age , race , and level of breast cancer risk . CONCLUSIONS Despite the potential bias caused by the unblinding of the P-1 trial , the magnitudes of all beneficial and undesirable treatment effects of tamoxifen were similar to those initially reported , with notable reductions in breast cancer and increased risks of thromboembolic events and endometrial cancer . Readily identifiable subsets of individuals comprising 2.5 million women could derive a net benefit from the drug Reconciling scientific research results with clinical practice represents a major challenge to healthcare professionals , including orthodontists.1 - 4 Current clinical decision-making should be mainly based on clinical trials comparing two or more treatment or diagnosis methods . These trials are known as r and omized controlled trials ( RCTs ) and are considered the gold st and ard in scientific evidence . The quality of RCTs can be assessed based on criteria pre-established by CONSORT ( Consoli date d St and ards of Reporting Trials).5 CONSORT is a protocol developed by a group of research ers not only to identify problems arising from conducting RCTs , but also to report , in a full and clear manner , the results yielded by research , thereby facilitating RCTs reading and quality assessment .5,6,7 It comprises a 25-item checklist focused on scientific article writing ( available at www.consort-statement.org ) . This checklist provides us with st and ards of how the trial was design ed , analyzed and interpreted . Thus , it consists in a useful tool that allows the research er to conduct a RCT and the clinical orthodontist to critically assess the quality of evidence provided . As a result , the orthodontist is able to employ treatment or diagnosis methods in his clinical practice in a safer and more reliable manner . In addition , he will be able to assess the quality of RCTs throughout its entire structure . In order to render analysis comprehension easier , the CONSORT checklist was divided into six categories , according to the parts of an article : 1 Title and abstract : the title should be concise and the word “ r and omized ” should be used . The abstract should be structured and include : trial design , methods , main results and conclusions . 2 Introduction : it should include a brief literature review , the rationale for the trial and the objective or hypothesis , all of which reported in a clear and objective manner . 3 – Method : it should be carefully reported as follows : trial design ; eligibility criteria for participants , with explanation of rationale for such criteria ; how and where data were collected ; thorough description of intervention , which allows results to be reproduced ; description of sample size calculation ; changes during the course of trial , with clear reasons ; thorough description of methods used for allocation into the trial groups , participants and evaluators blinding ; and proper statistical analysis . 4 Results : primary intervention results should be assessed for each group ; the number of Introduction Mammography screening results in a significant number of false-positives . The use of pretest breast cancer risk factors to guide follow-up of abnormal mammograms could improve the positive predictive value of screening . We evaluated the use of the Gail model , body mass index ( BMI ) , and genetic markers to predict cancer diagnosis among women with abnormal mammograms . We also examined the extent to which pretest risk factors could reclassify women without cancer below the biopsy threshold . Methods We recruited a prospect i ve cohort of women referred for biopsy with abnormal ( BI-RADS 4 ) mammograms according to the American College of Radiology ’s Breast Imaging-Reporting and Data System ( BI-RADS ) . Breast cancer risk factors were assessed prior to biopsy . A vali date d panel of 12 single-nucleotide polymorphisms ( SNPs ) associated with breast cancer were measured . Logistic regression was used to assess the association of Gail risk factors , BMI and SNPs with cancer diagnosis ( invasive or ductal carcinoma in situ ) . Model discrimination was assessed using the area under the receiver operating characteristic curve , and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test . The distribution of predicted probabilities of a cancer diagnosis were compared for women with or without breast cancer . Results In the multivariate model , age ( odds ratio ( OR ) = 1.05 ; 95 % confidence interval ( CI ) , 1.03 to 1.08 ; P < 0.001 ) , SNP panel relative risk ( OR = 2.30 ; 95 % CI , 1.06 to 4.99 , P = 0.035 ) and BMI ( ≥30 kg/m2 versus < 25 kg/m2 ; OR = 2.20 ; 95 % CI , 1.05 to 4.58 ; P = 0.036 ) were significantly associated with breast cancer diagnosis . Older women were more likely than younger women to be diagnosed with breast cancer . The SNP panel relative risk remained strongly associated with breast cancer diagnosis after multivariable adjustment . Higher BMI was also strongly associated with increased odds of a breast cancer diagnosis . Obese women ( OR = 2.20 ; 95 % CI , 1.05 to 4.58 ; P = 0.036 ) had more than twice the odds of cancer diagnosis compared to women with a BMI < 25 kg/m2 . The SNP panel appeared to have predictive ability among both white and black women . Conclusions Breast cancer risk factors , including BMI and genetic markers , are predictive of cancer diagnosis among women with BI-RADS 4 mammograms . Using pretest risk factors to guide follow-up of abnormal mammograms could reduce the burden of false-positive mammograms Prognostic classification schemes have often been used in medical applications , but rarely subjected to a rigorous examination of their adequacy . For survival data , the statistical methodology to assess such schemes consists mainly of a range of ad hoc approaches , and there is an alarming lack of commonly accepted st and ards in this field . We review these methods and develop measures of inaccuracy which may be calculated in a validation study in order to assess the usefulness of estimated patient-specific survival probabilities associated with a prognostic classification scheme . These measures are meaningful even when the estimated probabilities are misspecified , and asymptotically they are not affected by r and om censorship . In addition , they can be used to derive R(2)-type measures of explained residual variation . A breast cancer study will serve for illustration throughout the paper The Gail model is considered the best available means for estimating risk of breast cancer development , but it has not yet been applied systematic ally and vali date d in Turkish female population . This study was design ed to evaluate the performance of the Gail model for Turkish female population . Additionally duration of breastfeeding was examined as a possible risk factor . Our analysis included 650 patients with invasive breast carcinoma ( group 1 ) and 640 women with negative results who had undergone a screening mammography on visiting a mammary care unit ( group 2 ) . Two groups were compared with regard to individual risk factors included in the Gail model and also duration of breastfeeding . The Gail model was used to predict 5-year risk for each woman . Age and first live birth ≥30 years were associated with an increased relative risk for breast cancer development . Age at menarche , previous breast biopsy , atypical hyperplasia , and number of first degree relatives with breast cancer were found to be non-significant . The Gail model showed 13.3 % sensitivity and 92 % specificity in estimating the risk of breast cancer development in Turkish women . Positive predictive value was 63 % , negative predictive value was 51.9 % , and validity index was 53.1 % . Duration of breastfeeding was significantly longer in group 1 than 2 ( median 17 vs. 13 months ) . The proportion of parous women with no breastfed was higher in group 1 than 2 . The currently used Gail model does not seem to be an appropriate breast cancer risk assessment tool for Turkish female population Breast cancer remains a global health concern with a lack of high discriminating prediction models . The k-nearest-neighbor algorithm ( kNN ) estimates individual risks using an intuitive tool . This study compares the performances of this approach with the Cox and the Gail models for the 5-year breast cancer risk prediction . The study included 64,995 women from the French E3N prospect i ve cohort . The sample was divided into a learning ( N = 51,821 ) series to learn the models using fivefold cross-validation and a validation ( N = 13,174 ) series to evaluate them . The area under the receiver operating characteristic curve ( AUC ) and the expected over observed number of cases ( E/O ) ratio were estimated . In the two series , 393 and 78 premenopausal and 537 and 98 postmenopausal breast cancers were diagnosed . The discrimination values of the best combinations of predictors obtained from cross-validation ranged from 0.59 to 0.60 . In the validation series , the AUC values in premenopausal and postmenopausal women were 0.583 [ 0.520 ; 0.646 ] and 0.621 [ 0.563 ; 0.679 ] using the kNN and 0.565 [ 0.500 ; 0.631 ] and 0.617 [ 0.561 ; 0.673 ] using the Cox model . The E/O ratios were 1.26 and 1.28 in premenopausal women and 1.44 and 1.40 in postmenopausal women . The applied Gail model provided AUC values of 0.614 [ 0.554 ; 0.675 ] and 0.549 [ 0.495 ; 0.604 ] and E/O ratios of 0.78 and 1.12 . This study shows that the prediction performances differed according to menopausal status when using parametric statistical tools . The k-nearest-neighbor approach performed well , and discrimination was improved in postmenopausal women compared with the Gail model Results from several r and omised mammography screening trials haveshown that it is possible to reduce mortalityin breast cancer by mammographic screening at leastfor women above 50 years of age . The purpose of this article is to present data on mortality in breast cancer in study and control groups of the Stockholm trial after 11years of followup , to analyse which age group benefits most from screening . In March 1981 , 40,318women in Stockholm , aged 40 through 64 years , entered a r and omized trial of breast cancer screeningby single view mammography alone , versus no interventionin a control group of 20 000 women . Two screening rounds were performed and the attendancerate was over 80 % in the two rounds . During 1986 the control group was invited onceto screening . Totally 428 and 217 cases ofbreast cancer were diagnosed in the study and control groups respectively . After a mean follow-up of11.4 years a nonsignificant mortality reduction of 26%was observed for the whole study group , witha relative risk ( RR ) of death in breastcancer of 0.74 ( CI(confidence interval)=0.5–1.1 ) . Forwomen aged 50–64 years a significant 38 % mortalityreduction was observed with a RR of 0.62(CI=0.38–1.0 ) . For women aged 40–49 yearsno effect on mortality was found , with aRR of death in breast cancer of 1.08(CI=0.54–2.17 ) . The breakpoint for benefit inthis study seemed to be at 50 yearsof age when 5-year age groups were analysed , but this tendency is uncertain because of thelow statistical power in the analysis of theyounger age groups . Long screening intervals , the useof single-view mammography , and the fact that morethan 50 % of the women in age group40–49 years were still below 50 years ofage when the study was closed , were allfacts that could have influenced the results inage group 40–49 years . Larger studies are neededto answer the question whether mammographic screening canbe successful in younger age groups STUDY OBJECTIVE --To determine whether mortality from breast cancer could be reduced by repeated mammographic screening . DESIGN --Birth year cohorts of city population separately r and omised into study and control groups . SETTING --Screening clinic outside main hospital . PATIENTS --Women aged over 45 ; 21,088 invited for screening and 21,195 in control group . INTERVENTIONS --Women in the study group were invited to attend for mammographic screening at intervals of 18 - 24 months . Five rounds of screening were completed . Breast cancer was treated according to stage at diagnosis . END POINT -- Mortality from breast cancer . MEASUREMENTS AND MAIN RESULTS --All women were followed up and classed at end point as alive without breast cancer , alive with breast cancer , dead from breast cancer , or dead from other causes . Cause of death was taken from national mortality registry and for patients with breast cancer was vali date d independently . Mean follow up was 8.8 years . Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group ; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer ( no significant difference ; relative risk 0.96 ( 95 % confidence interval 0.68 to 1.35 ) ) . In the study group 29 % more women aged less than 55 died of breast cancer ( 28 v 22 ; relative risk 1.29 ( 0.74 to 2.25 ) ) . More women in the study group died from breast cancer in the first seven years ; after that the trend reversed , especially in women aged greater than or equal to 55 at entry . Overall , women in the study group aged greater than or equal to 55 had a 20 % reduction in mortality from breast cancer ( 35 v 44 ; relative risk 0.79 ( 0.51 to 1.24 ) ) . OTHER FINDINGS --In the study group 100 ( 17 % ) cancers appeared in intervals between screenings and 107 ( 18 % ) in non-attenders ; 51 of these women died from breast cancer . Cancers classed as stages II-IV comprised 33 % ( 190/579 ) of cancers in the study group and 52 % ( 231/443 ) in the control group . CONCLUSIONS --Invitation to mammographic screening may lead to reduced mortality from breast cancer , at least in women aged 55 or over Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial . Five studies have been done in Sweden . This overview , based on 282,777 women followed for 5 - 13 years in r and omised trials in Malmö , Kopparberg , Ostergötl and , Stockholm , and Gothenburg , reveals a 24 % ( 95 % confidence interval 13 - 34 % ) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited . To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases . The mortality reduction was similar , irrespective of the end-point used for evaluation ( " breast cancer as underlying cause of death " or " breast cancer present at death " ) . There was a consistent risk reduction associated with screening in all studies , although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84 . The cumulative breast cancer mortality by time since r and omisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group . The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1 . The largest reduction of breast cancer mortality ( 29 % ) was observed among women aged 50 - 69 at r and omisation . Among women 40 - 49 there was a non-significant 13 % reduction . In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up . After 8 years there was a difference in favour of the invited women . There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group . Among women aged 70 - 74 years screening seems to have had only a marginal impact BACKGROUND The Edinburgh r and omised trial of breast-cancer screening recruited women aged 45 - 64 years from 1978 to 1981 ( cohort 1 ) , and those aged 45 - 49 years during 1982 - 85 ( cohorts 2 and 3 ) . Results based on 14 years of follow-up and 270,000 woman-years of observation are reported . METHODS Breast-cancer mortality rates in the intervention group ( 28,628 women offered screening ) were compared with those in the control group ( 26,026 ) with adjustment for socioeconomic status ( SES ) of general medical practice s. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years . Analyses were by intention to treat . FINDINGS Initial unadjusted results showed a difference of just 13 % in breast-cancer mortality rates between the intervention and control groups ( 156 deaths [ 5.18 per 10,000 ] vs 167 [ 6.04 per 10,000 ] ; rate ratio 0.87 [ 95 % CI 0.70 - 1.06 ] ) , but the results were influenced by differences in SES by trial group . After adjustment for SES , the rate ratio was 0.79 ( 95 % CI 0.60 - 1.02 ) . When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 ( 0.53 - 0.95 ) . There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit ( rate ratio 0.70 [ 0.41 - 1.20 ] ) . No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years . Other-cause mortality rates did not differ by trial group when adjusted for SES . INTERPRETATION Our findings confirm results from r and omised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality . Similar results are reported by the UK geographical comparison , UK Trial of Early Detection of Breast Cancer . The results for younger women suggest benefit from introduction of screening before 50 years of age OBJECTIVES The aims of this study were to estimate the 5-year breast cancer risk in indigent women presenting to the gynecology clinic at a public hospital and to determine whether routine use of the computerized Gail model for screening in this population identifies individuals at increased risk . METHODS A prospect i ve study was performed over 1-year period ( 7/99 - 7/00 ) of women presenting to the gynecology and gynecologic oncology clinics at a public hospital . All women ages 35 - 60 years with no personal history of breast cancer were offered testing utilizing the computerized Gail model provided by the National Cancer Institute . Age , race , age at menarche , age at first live birth , number of first-degree relatives with breast cancer , number of breast biopsies , and number of breast biopsies diagnosed as atypical hyperplasia were documented . A calculated 5-year risk > or = 1.67 % was considered high-risk . RESULTS In all , 319 women enrolled , 121 ( 38 % ) with a history of gynecologic cancer and 198 ( 62 % ) without . The mean age was 46.9 years ( range 35 - 60 ) , and 28 ( 8.8 % ) patients had at least one first-degree relative with breast cancer . Ethnicity included 206 ( 65 % ) African American , 52 ( 16 % ) Caucasian , 45 ( 14 % ) Hispanic , and 16 ( 5 % ) oriental . Eight ( 2.5 % ) women had a 5-year risk > or = 1.67 % . The mean 5-year risk for all patients was 0.68 % ( 0.55 % for African American versus 0.90 % for Caucasian/other , P < 0.001 ) . CONCLUSION Estimating 5-year breast cancer risk using the Gail model in indigent women may identify individuals at increased risk . Compared to other patients , African American women appeared to have a lower estimated 5-year risk according to the currently available model . The routine utilization of the Gail model deserves further investigation in the indigent minority population Background . Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women . Various possible reasons have been suggested for this , but none firmly is established Periodic breast cancer screening with mammography and clinical examination is being evaluated to determine its value in reducing breast cancer mortality among women . Representative sample s of women aged 40 to 64 years enrolled in the Health Insurance Plan of Greater New York are r and omly assigned to study and control groups , each of which will contain 30,000 women . Results of the study to date are consistent with the hypothesis that the screening leads to earlier detection of breast cancers than is ordinarily experienced and that mammography contributes significantly to detection . While these relationships are encouraging , they must be viewed with caution since the study is still in its early stages . Furthermore , the crucial question is whether mortality from breast cancer is lowered because of the screening , and definitive findings on this issue will require at least five years of follow-up BACKGROUND Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer . However , the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known . This study was design ed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only . Breast self-examination was taught to all participants . METHODS This trial r and omly and individually assigned 39 405 women aged 50 - 59 years , recruited from January 1980 through March 1985 , to one of the study arms . The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Data base to December 31 , 1993 , and by active follow-up of breast cancer patients to June 30 , 1996 . RESULTS R and omization achieved virtually equal distribution of demographic and breast cancer risk variables . At the first annual screen , 21 % of the cancers found by mammography alone ( in the mammography plus physical examination group ) were 20 mm or more in size compared with 46 % of those found by physical examination in the mammography plus physical examination group and 56 % in the physical examination-only group . The corresponding percentages for screens 2 - 5 were 10 % , 42 % , and 50 % , respectively . Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group . By December 31 , 1993 , 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group , and 610 and 16 were ascertained in the physical examination-only group . At 13-year follow-up , with 107 and 105 deaths from breast cancer in the respective groups , the cumulative rate ratio was 1.02 ( 95 % confidence interval = 0.78 - 1.33 ) . CONCLUSION In women aged 50 - 59 years , the addition of annual mammography screening to physical examination has no impact on breast cancer mortality Background Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening . Premenopausal concentrations of circulating anti-Müllerian hormone ( AMH ) , a biomarker of ovarian reserve , and testosterone have been positively associated with breast cancer risk in prospect i ve studies . We assessed whether adding AMH and /or testosterone to the Gail model improves its prediction performance for women aged 35–50 . Methods In a nested case-control study including ten prospect i ve cohorts ( 1762 invasive cases/1890 matched controls ) with pre-diagnostic serum/plasma sample s , we estimated relative risks ( RR ) for the biomarkers and Gail risk factors using conditional logistic regression and r and om-effects meta- analysis . Absolute risk models were developed using these RR estimates , attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium , and population -based incidence and mortality rates . The area under the receiver operating characteristic curve ( AUC ) was used to compare the discriminatory accuracy of the models with and without biomarkers . Results The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 ( 95 % CI 53.4 , 57.1 ) . The AUC increased moderately with the addition of AMH ( AUC 57.6 , 95 % CI 55.7 , 59.5 ) , testosterone ( AUC 56.2 , 95 % CI 54.4 , 58.1 ) , or both ( AUC 58.1 , 95 % CI 56.2 , 59.9 ) . The largest AUC improvement ( 4.0 ) was among women without a family history of breast cancer . Conclusions AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35–50 . We observed the largest AUC increase for women without a family history of breast cancer , the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history |
11,281 | 25,925,354 | Conclusions The majority of studies suggest that EFV quantification is significantly associated with clinical outcomes and provides incremental prognostic value over coronary artery calcium scoring .
Future research should use a binary cutoff of 125 mL for evaluation of EFV to provide consistency with other research .Key Points• Epicardial fat volume ( EFV ) has prognostic value for adverse cardiac events • Establishment of st and ardized quantitative categories for EFV is needed • Quantification of EFV could improve risk assessment with calcium | Abstract Objectives To perform a systematic review of the growing body of literature evaluating the prognostic value of epicardial fat volume ( EFV ) quantified by cross-sectional imaging . | OBJECTIVES This study sought to determine whether epicardial fat volume predicts coronary events in the general population . BACKGROUND Epicardial adipose tissue ( EAT ) is suggested to promote plaque development in the coronary artery tree . METHODS We quantified EAT volume in participants from the prospect i ve population -based Heinz Nixdorf Recall cohort study free of cardiovascular disease . Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years . Multivariable association of EAT with cardiovascular risk factors , coronary artery calcification ( CAC ) , and coronary events was assessed using regression analysis . RESULTS From the overall 4,093 participants ( age 59.4 years , 47 % male ) , 130 subjects developed a fatal or nonfatal coronary event . Incidence of coronary events increased by quartile of EAT ( 0.9 % vs. 4.7 % for 1(st ) and 4th quartile , respectively , p < 0.001 ) . Doubling of EAT was associated with a 1.5-fold risk of coronary events when adjusting for cardiovascular risk factors ( hazard ratio [ HR ] [ 95 % confidence interval ( CI ) ] : 1.54 [ 1.09 to 2.19 ] ) , which remained unaltered after further adjustment for CAC score ( HR [ 95 % CI ] : 1.50 [ 1.07 to 2.11 ] ) . For discrimination of subjects with events from those without , we observed a trend for improvement of Harrell 's C and explained variance by EAT over traditional cardiovascular risk factors , which , however , did not reach statistical significance ( 0.720 to 0.730 for risk factors alone and with EAT added , respectively , p = 0.10 , R(2 ) = 2.73 % to R(2 ) = 2.92 % , time-dependent integrated discrimination improvement = 0.196 % ) . CONCLUSIONS Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score OBJECTIVES The aim of this study was to determine whether ectopic fat depots are prospect ively associated with cardiovascular disease , cancer , and all-cause mortality . BACKGROUND The morbidity associated with excess body weight varies among individuals of similar body mass index . Ectopic fat depots may underlie this risk differential . However , prospect i ve studies of directly measured fat are limited . METHODS Participants from the Framingham Heart Study ( n = 3,086 ; 49 % women ; mean age of 50.2 years ) underwent assessment of fat depots ( visceral adipose tissue , pericardial adipose tissue , and periaortic adipose tissue ) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years . Cox proportional hazards regression models were used to examine the association of each fat depot ( per 1 SD increment ) with the risk of incident cardiovascular disease , cancer , and all-cause mortality after adjustment for st and ard risk factors , including body mass index . RESULTS Overall , there were 90 cardiovascular events , 141 cancer events , and 71 deaths . After multivariable adjustment , visceral adipose tissue was associated with cardiovascular disease ( hazard ratio : 1.44 ; 95 % confidence interval : 1.08 to 1.92 ; p = 0.01 ) and cancer ( hazard ratio : 1.43 ; 95 % confidence interval : 1.12 to 1.84 ; p = 0.005 ) . Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction ( net reclassification improvement of 16.3 % ) . None of the fat depots were associated with all-cause mortality . CONCLUSIONS Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity . These findings support the growing appreciation of a pathogenic role of ectopic fat Background —Noncontrast cardiac computed tomography allows calculation of coronary artery calcium score ( CACS ) and measurement of epicardial adipose tissue ( EATv ) and intrathoracic fat ( ITFv ) volumes . It is unclear whether fat volume information contributes to risk stratification . Methods and Results —Cardiac computed tomography was performed in 760 consecutive patients with acute chest pain admitted thorough the emergency department . None had prior coronary artery disease . CACS was calculated using the Agatston method . EATv and ITFv were semiautomatically calculated . Median patient follow-up was 3.3 years . Mean patient age was 54.4±13.7 years and Framingham risk score 8.2±8.2 . The 45 patients ( 5.9 % ) with major acute cardiac events ( MACE ) were older ( 64.8±13.9 versus 53.7±13.4 years ) , more frequently male ( 60 % versus 40 % ) , and had a higher median Framingham risk score ( 16 versus 4 ) and CACS ( 268 versus 0 ) versus those without events ( all P<0.01 ) . The MACE group had a higher median of EATv ( 154 versus 116 mL ) and ITFv ( 330 versus 223 mL ) , and a higher prevalence of EATv > 125 mL ( 67 % versus 44 % ) and ITFv > 250 mL ( 64 % versus 42 % ) ( all P<0.01 ) . CACS , EATv , and ITFv were all independently associated with MACE . CACS was associated with MACE after adjustment for fat volumes ( P<0.0001 ) , whereas EATv and ITFv improved the risk model only in patients with CACS > 400 . Conclusions —CACS and fat volumes are independently associated with MACE in acute chest pain patients and beyond that provided by clinical information alone . Although fat volumes may add prognostic value in patients with CACS > 400 , CACS is most strongly correlated with outcome BACKGROUND Epicardial adipose tissue ( EAT ) has been described in the general population as an independent risk marker for incident coronary artery disease . In hemodialysis patients , it correlates with other markers of cardiovascular disease , but it is unknown if it is associated with adverse events . METHODS post hoc analysis of the Renagel in New Dialysis ( RIND ) patients study , a r and omized trial of sevelamer versus calcium-based phosphate binders in 109 incident hemodialysis patients , followed for all-cause mortality for a median of 49.3 months . Patients underwent baseline cardiac computed tomography imaging within 120 days of dialysis initiation . RESULTS Baseline EAT measurements were available in 95 patients ; EAT was positively correlated with age , body mass index , triglycerides , C-reactive protein , coronary artery calcium and aortic calcium , and negatively correlated with systolic and diastolic blood pressure , serum high density lipoprotein ( HPL ) cholesterol and serum phosphate ( all P < 0.05 ) . During follow-up , a total of 27 ( 28.4 % ) patients expired [ mortality per 1000 patients /year : 95 % confidence interval ( 95 % CI ) = 77 ( 64 - 94 ) ] . Five-year survival rate was 44 . 6 % ( 95 % CI : 21.1 - 65.7 ) and 71.2 % ( 95 % CI : 45.95 - 86.25 ) in patients with EAT above or below the median , respectively . Each 10 cc increase in EAT volume was associated with a significant 6 % increase in the risk of death during follow-up [ hazard ratio ( HR ) : 1.060 ; 95 % CI : 1.013 - 1.109 ; P-value = 0.012 ] . CONCLUSIONS In this sub analysis of a r and omized trial , EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up . These hypothesis-generating findings will need confirmatory evidence BACKGROUND Coronary artery disease ( CAD ) diagnosis by coronary computed tomographic angiography ( CCTA ) is useful for identification of symptomatic diabetic individuals at heightened risk for death . Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring ( CACS ) remains unexplored . METHODS From a prospect i ve 12-center international registry of 27,125 individuals undergoing CCTA , we identified 400 asymptomatic diabetic individuals without known CAD . Coronary stenosis by CCTA was grade d as 0 % , 1 - 49 % , 50 - 69 % , and ≥70 % . CAD was judged on a per-patient , per-vessel and per-segment basis as maximal stenosis severity , number of vessels with ≥50 % stenosis , and coronary segments weighted for stenosis severity ( segment stenosis score ) , respectively . We assessed major adverse cardiovascular events ( MACE ) - inclusive of mortality , nonfatal myocardial infa rct ion ( MI ) , and late target vessel revascularization ≥90 days ( REV ) - and evaluated the incremental utility of CCTA for risk prediction , discrimination and reclassification . RESULTS Mean age was 60.4 ± 9.9 years ; 65.0 % were male . At a mean follow-up 2.4 ± 1.1 years , 33 MACE occurred ( 13 deaths , 8 MI , 12 REV ) [ 8.25 % ; annualized rate 3.4 % ] . By univariate analysis , per-patient maximal stenosis [ hazards ratio ( HR ) 2.24 per stenosis grade , 95 % confidence interval ( CI ) 1.61 - 3.10 , p < 0.001 ] , increasing numbers of obstructive vessels ( HR 2.30 per vessel , 95 % CI 1.75 - 3.03 , p < 0.001 ) and segment stenosis score ( HR 1.14 per segment , 95 % CI 1.09 - 1.19 , p < 0.001 ) were associated with increased MACE . After adjustment for CAD risk factors and CACS , maximal stenosis ( HR 1.80 per grade , 95 % CI 1.18 - 2.75 , p = 0.006 ) , number of obstructive vessels ( HR 1.85 per vessel , 95 % CI 1.29 - 2.65 , p < 0.001 ) and segment stenosis score ( HR 1.11 per segment , 95 % CI 1.05 - 1.18 , p < 0.001 ) were associated with increased risk of MACE . Beyond age , gender and CACS ( C-index 0.64 ) , CCTA improved discrimination by maximal stenosis , number of obstructive vessels and segment stenosis score ( C-index 0.77 , 0.77 and 0.78 , respectively ) . Similarly , CCTA findings improved risk reclassification by per-patient maximal stenosis [ integrated discrimination improvement ( IDI ) index 0.03 , p = 0.03 ] and number of obstructive vessels ( IDI index 0.06 , p = 0.002 ) , and by trend for segment stenosis score ( IDI 0.03 , p = 0.06 ) . CONCLUSION For asymptomatic diabetic individuals , CCTA measures of CAD severity confer incremental risk prediction , discrimination and reclassification on a per-patient , per-vessel and per-segment basis BACKGROUND Pericardial fat ( ie , fat around the heart ) may have a direct role in the atherosclerotic process in coronary arteries through local release of inflammation-related cytokines . Cross-sectional studies suggest that pericardial fat is positively associated with coronary artery disease independent of total body fat . OBJECTIVE We investigated whether pericardial fat predicts future coronary heart disease events . DESIGN We conducted a case-cohort study in 998 individuals , who were r and omly selected from 6814 Multi-Ethnic Study of Atherosclerosis ( MESA ) participants and 147 MESA participants ( 26 from those 998 individuals ) who developed incident coronary heart disease from 2000 to 2005 . The volume of pericardial fat was determined from cardiac computed tomography at baseline . RESULTS The age range of the subjects was 45 - 84 y ( 42 % men , 45 % white , 10 % Asian American , 22 % African American , and 23 % Hispanic ) . Pericardial fat was positively correlated with both body mass index ( correlation coefficient = 0.45 , P < 0.0001 ) and waist circumference ( correlation coefficient = 0.57 , P < 0.0001 ) . In unadjusted analyses , pericardial fat ( relative hazard per 1-SD increment : 1.33 ; 95 % CI : 1.15 , 1.54 ) , but not body mass index ( 1.00 ; 0.84 , 1.18 ) , was associated with the risk of coronary heart disease . Waist circumference ( 1.14 ; 0.97 , 1.34 ; P = 0.1 ) was marginally associated with the risk of coronary heart disease . The relation between pericardial fat and coronary heart disease remained significant after further adjustment for body mass index and other cardiovascular disease risk factors ( 1.26 ; 1.01 , 1.59 ) . The relation did not differ by sex . CONCLUSION Pericardial fat predicts incident coronary heart disease independent of conventional risk factors , including body mass index |
11,282 | 27,208,380 | Carbohydrate ( glucose and fructose ) , lipid ( phospholipids , sphingomyelins , and triglycerides ) , and amino acid ( branched-chain amino acids , aromatic amino acids , glycine , and glutamine ) metabolites were higher in individuals with type 2 diabetes compared with control subjects .
Prospect i ve studies provided evidence that blood concentrations of several metabolites , including hexoses , branched-chain amino acids , aromatic amino acids , phospholipids , and triglycerides , were associated with the incidence of prediabetes and type 2 diabetes .
In studies using high-throughput metabolomics , several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes | OBJECTIVE To conduct a systematic review of cross-sectional and prospect i ve human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes . | OBJECTIVE 1,5-Anhydroglucitol ( 1,5AG ) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose . Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies . In this first U.S. study , we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes ( 22 with type 1 diabetes , 55 with type 2 diabetes ) who presented with suboptimal glycemic control at baseline ( defined as HbA(1c ) > or=7 % ) . RESEARCH DESIGN AND METHODS Each patient received therapies consisting of combinations of diabetes education , nutritional counseling , and addition or dose adjustment of various insulins or oral antihyperglycemic medications . Therapy was targeted to reduce mean HbA(1c ) by > or=1.0 % over the monitoring period . 1,5AG , HbA(1c ) , fructosamine , and r and om glucose measurements were performed at baseline and at 2 , 4 , and 8 weeks after the initiation of therapy . RESULTS 1,5AG , fructosamine , and glucose values progressed significantly toward euglycemia by week 2 of monitoring ( Wilcoxon 's signed-rank test , P < 0.05 ) , with median changes of 93 , -7 , and -13 % for 1,5AG , fructosamine , and glucose , respectively . In contrast , HbA(1c ) values did not respond significantly to therapy until week 4 . On an individual patient basis , 89.6 % of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA(1c ) . 1,5AG was also highly correlated with HbA(1c ) and fructosamine ( Spearman rho = -0.6459 and -0.6751 , respectively ; both P < 0.0001 ) . CONCLUSIONS We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers 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 OBJECTIVE Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes ; however , the underlying mechanisms remain elusive . We tested whether amino acids predict insulin resistance index in healthy young adults . RESEARCH DESIGN AND METHODS Circulating isoleucine , leucine , valine , phenylalanine , tyrosine , and six additional amino acids were quantified in 1,680 individuals from the population -based Cardiovascular Risk in Young Finns Study ( baseline age 32 ± 5 years ; 54 % women ) . Insulin resistance was estimated by homeostasis model assessment ( HOMA ) at baseline and 6-year follow-up . Amino acid associations with HOMA of insulin resistance ( HOMA-IR ) and glucose were assessed using regression models adjusted for established risk factors . We further examined whether amino acid profiling could augment risk assessment of insulin resistance ( defined as 6-year HOMA-IR > 90th percentile ) in early adulthood . RESULTS Isoleucine , leucine , valine , phenylalanine , and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up , while for women only leucine , valine , and phenylalanine predicted 6-year HOMA-IR ( P < 0.05 ) . None of the other amino acids were prospect ively associated with HOMA-IR . The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men ( odds ratio 2.09 [ 95 % CI 1.38–3.17 ] ; P = 0.0005 ) ; however , including the amino acid score in prediction models did not improve risk discrimination . CONCLUSIONS Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young , normoglycemic adults , with most pronounced associations for men . These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance Plasma concentrations of amino acids are frequently elevated in insulin-resistant states , and a protein-enriched diet can impair glucose metabolism . This study examined effects of short-term plasma amino acid ( AA ) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle . Seven healthy men were studied for 5.5 h during euglycemic ( 5.5 mmol/l ) , hyperinsulinemic ( 430 pmol/l ) , fasting glucagon ( 65 ng/l ) , and growth hormone ( 0.4 microg/l ) somatostatin clamp tests in the presence of low ( approximately 1.6 mmol/l ) and increased ( approximately 4.6 mmol/l ) plasma AA concentrations . Glucose turnover was measured with D-[6,6-(2)H(2)]glucose . Intramuscular concentrations of glycogen and glucose-6-phosphate ( G6P ) were monitored using (13)C and (31)P nuclear magnetic resonance spectroscopy , respectively . A approximately 2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25 % ( P < 0.01 ) . Rates of muscle glycogen synthesis decreased by 64 % ( 180 - -315 min , 24 plus minus 3 ; control , 67 plus minus 10 micromol center dot l(-1 ) center dot min(-1 ) ; P < 0.01 ) , which was accompanied by a reduction in G6P starting at 130 min ( DeltaG6P(260 - -300 min ) , 18 plus minus 19 ; control , 103 plus minus 33 micromol/l ; P < 0.05 ) . In conclusion , plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation , result ing in marked reduction of glycogen synthesis Background Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression . Current diagnostic tests , such as glycemic indicators , have limitations in the early detection of insulin resistant individuals . We search ed for novel biomarkers identifying these at-risk subjects . Methods Using mass spectrometry , non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance ( based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing , respectively ) . Results R and om forest statistical analysis selected α-hydroxybutyrate ( α – HB ) as the top-ranked biochemical for separating insulin resistant ( lower third of the clamp-derived MFFM = 33 [ 12 ] µmol·min−1·kgFFM −1 , median [ interquartile range ] , n = 140 ) from insulin sensitive subjects ( MFFM = 66 [ 23 ] µmol·min−1·kgFFM −1 ) with a 76 % accuracy . By targeted isotope dilution assay , plasma α – HB concentrations were reciprocally related to MFFM ; and by partition analysis , an α – HB value of 5 µg/ml was found to best separate insulin resistant from insulin sensitive subjects . α – HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of , and in an additive fashion to , insulin resistance . These associations were also independent of sex , age and BMI . Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid , amino acid , lysophospholipid , acylcarnitine and fatty acid species . Several metabolites are intermediates related to α-HB metabolism and bio synthesis . Conclusions α – hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation . The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress Background : Insulin resistance ( IR ) can precede the dysglycemic states of prediabetes and type 2 diabetes mellitus ( T2DM ) by a number of years and is an early marker of risk for metabolic and cardiovascular disease . There is an unmet need for a simple method to measure IR that can be used for routine screening , prospect i ve study , risk assessment , and therapeutic monitoring . We have reported several metabolites whose fasting plasma levels correlated with insulin sensitivity . These metabolites were used in the development of a novel test for IR and prediabetes . Methods : Data from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study were used in an iterative process of algorithm development to define the best combination of metabolites for predicting the M value derived from the hyperinsulinemic euglycemic clamp , the gold st and ard measure of IR . Subjects were divided into a training set and a test set for algorithm development and validation . The result ing calculated M score , MQ , was utilized to predict IR and the risk of progressing from normal glucose tolerance to impaired glucose tolerance ( IGT ) over a 3 year period . Results : MQ correlated with actual M values , with an r value of 0.66 . In addition , the test detects IR and predicts 3 year IGT progression with areas under the curve of 0.79 and 0.70 , respectively , outperforming other simple measures such as fasting insulin , fasting glucose , homeostatic model assessment of IR , or body mass index . Conclusions : The result , Quantose ™ , is a simple test for IR based on a single fasting blood sample and may have value as an early indicator of risk for the development of prediabetes and T2DM |
11,283 | 27,260,682 | Conclusion The pooled analysis revealed that regardless of intensity , volume , type of exercise , and studied population , the antioxidant indicators tended to increase and pro-oxidant indicators tended to decrease after training .
Therefore , we conclude that exercise training seems to induce an antioxidant effect .
Thus , it is suggested that people practice some kind of exercise to balance the redox state , regardless of their health status , to improve health-related outcomes | Background Physical activity has been associated with reduced oxidative stress ( OS ) in observational studies and clinical trials .
Objective The purpose of this systematic review and meta- analysis of controlled trials was to determine the effect of physical exercise on OS parameters . | This study was undertaken to investigate the effects of progressive resistance-training ( PRT ) on plasma oxidative stress and antioxidant enzyme activity in erythrocytes . Twenty male volunteers were r and omly assigned to 2 groups : PRT and control . Blood sample s were collected before and after 8 wk of PRT and analyzed for enzymatic activities of superoxide dismutase ( SOD ) and glutathione peroxidase ( GPx ) in erythrocytes , plasma total antioxidant capacity ( TAC ) , and malondialdehyde concentration ( MDA , an index of lipid per oxida- tion in plasma ) . Resistance training commenced with 8 exercises on nonconsecutive days for 8 wk at 50 % of estimated 1-repetition maximum ( E1RM ) and reached 80 % E1RM by Week 8 . The results showed that PRT significantly increased erythrocyte SOD activity ( 1,323 ± 212.52 vs. 1,449.9 ± 173.8 U/g Hb , p = .014 ) . Plasma concentration of MDA also decreased ( 5.39 ± 1.7 vs. 3.67.4 ± 0.7 nmol/ml , p = .030 ) , although TAC ( 1.42 ± 0.21 vs. 1.61 ± 0.19 mmol/L , p = .1530 ) and GPx ( 39.87 ± 11.5 vs. 48.18 ± 14.48 U/g Hb , p = .883 ) activity did not undergo any considerable changes . Based on these data , the authors conclude that an 8-wk program of PRT strengthens the defensive system of erythrocytes against free-radical damage and therefore can be applied as a useful approach to alleviate oxidative stress Objective To determine the effect of Tai Chi on oxidative stress in a population of elderly Mexican subjects . Design It was carried out a quasi-experimental study with a sample of 55 healthy subjects r and omly divided into two age-matched groups : ( i ) a control group with 23 subjects and ( ii ) an experimental group with 32 subjects . The experimental group received daily training in Tai Chi for 50 min . Measurements It was measured before and after 6-month of exercise period : thiobarbituric acid reactive substances ( TBARS ) , total antioxidant status ( TAS ) , superoxide dismutase ( SOD ) , and glutathione peroxidase ( GPx ) . Results It was found that the experimental group exhibited a statistically significant decrease in glucose levels , total cholesterol , low-density lipoprotein cholesterol ( LDLC ) , and systolic blood pressure , as well as an increase in SOD and GPx activity and TAS compared with the control group ( p < 0.05 ) . Conclusions Our findings suggest that the daily practice of Tai Chi is useful for reducing OxS in healthy older adults Prehypertension is associated with reduced conduit artery endothelial function and perturbation of oxidant/antioxidant status . It is unknown whether endothelial dysfunction persists to resistance arteries and whether exercise training affects oxidant/antioxidant balance in young prehypertensives . We examined resistance artery function using venous occlusion plethysmography measurement of forearm ( FBF ) and calf blood flow ( CBF ) at rest and during reactive hyperaemia ( RH ) , as well as lipid peroxidation ( 8-iso-PGF2α ) and antioxidant capacity ( Trolox-equivalent antioxidant capacity ; TEAC ) before and after exercise intervention or time control . Forty-three unmedicated prehypertensive and 15 matched normotensive time controls met screening requirements and participated in the study ( age : 21.1±0.8 years ) . Prehypertensive subjects were r and omly assigned to resistance exercise training ( PHRT ; n=15 ) , endurance exercise training ( PHET ; n=13 ) or time-control groups ( PHTC ; n=15 ) . Treatment groups exercised 3 days per week for 8 weeks . Peak and total FBF were lower in prehypertensives than normotensives ( 12.7±1.2 ml min−1 per100 ml tissue and 89.1±7.7 ml min−1 per 100 ml tissue vs 16.3±1.0 ml min−1 per 100 ml tissue and 123.3±6.4 ml min−1 per 100 ml tissue , respectively ; P<0.05 ) . Peak and total CBF were lower in prehypertensives than normotensives ( 15.3±1.2 ml min−1 per 100 ml tissue and 74±8.3 ml min−1 per 100 ml tissue vs 20.9±1.4 ml min−1 per 100 ml tissue and 107±9.2 ml min−1 per 100 ml tissue , respectively ; P<0.05 ) . PHRT and PHET improved humoral measures of TEAC ( + 24 and + 30 % ) and 8-iso-PGF2α ( −43 and −40 % , respectively ; P⩽0.05 ) . This study provides evidence that young prehypertensives exhibit reduced resistance artery endothelial function and that short-term ( 8 weeks ) resistance or endurance training are effective in improving resistance artery endothelial function and oxidant/antioxidant balance in young prehypertensives BACKGROUND there have been few population -based , r and omized controlled trials on the effects of strength or endurance training on cardiovascular fitness in older women . OBJECTIVE to study the effects of strength or endurance training on cardiovascular fitness in women aged 76 - 78 years . DESIGN a population -based , r and omized controlled trial . SETTING exercise laboratory in a university faculty of sport and health sciences . SUBJECTS we r and omly assigned 42 medically-screened women aged 76 - 78 years , drawn from the population register to strength ( n=16 ) , endurance ( n=15 ) or control ( n=11 ) groups . METHODS subjects in the two exercise groups performed a supervised , individually tailored 18-week strength or endurance training programme . Controls continued with physical activity at their normal level . RESULTS the strength training group showed an increase in cycle ergometer peak power from 68.1 to 70.3 W ( P=0.035 compared with controls ) . Their peak power per kg body weight increased from 1.02 to 1.05 , while that of the endurance training group increased from 0.91 to 0.93 ( P=0.027 and P=0.049 respectively ) . Peak oxygen uptake increased from 18.1 to 19.7 ml x kg(-1 ) x min(-1 ) in the strength and from 17.1 to 18.2 in the endurance group ( non-significant ) . Six subjects ( 19 % ) in the exercise groups withdrew from the study because of health problems . CONCLUSIONS even with its limitations , the study suggests that the effect of 18-week strength or endurance training on cardiovascular fitness among women aged > /=75 is relatively small . Furthermore , health problems can emerge during training programmes in medically-screened elderly women The purpose of this trial was to determine whether exercise without weight loss would reduce F2-isoprostanes in previously sedentary young women . Participants ( N=319 ) were r and omized to four months of 150min/week aerobic exercise or a control group . Plasma free F2-isoprostanes were measured by gas chromatography-mass spectrometry . Other assessment s included fitness and % body fat . Intervention groups were compared with stratification by quartiles of baseline plasma F2-isoprostane . This stratified comparison was linearly adjusted for baseline plasma F2-isoprostane and we also used baseline plasma F2-isoprostane as a propensity score to balance the intervention . Training result ed in significant improvements in aerobic fitness ( 0.88 METs ) and body fat percent ( 1 % ) in exercisers compared to controls ( p<0.001 ) . The exercise group had significantly higher mean baseline plasma F2-isoprostanes ( 79.1 vs 67.9pg/mL ) than the control group in the highest quartile of baseline plasma F2-isoprostanes . Within this highest quartile , exercise led to a greater decline in plasma F2-isoprostanes ( -20.2±2.5pg/mL ) than control ( -7.4±2.5pg/mL ) ; with adjustment for baseline plasma F2-isoprostanes and in the balanced groups , this difference was reduced but remained significant . Four months of exercise training result ed in significant reductions of systemic oxidative stress only among previously sedentary young women who were in the highest quartile of plasma F2-isoprostanes at baseline ( ≥57pg/mL ) . Our findings indicate that the benefits of aerobic exercise in reducing systemic oxidative stress may be limited to those who present higher baseline levels of plasma F2-isoprostanes OBJECTIVE To assess the effect of a 12-week arm-cranking exercise program on reducing oxidative damage in untrained adults with chronic spinal cord injury ( SCI ) . DESIGN R and omized controlled trial . SETTING Community-based supervised intervention . PARTICIPANTS Male adults with complete SCI at or below the fifth thoracic level ( T5 ) ( N=17 ) volunteered for this study . Participants were r and omly allocated to the intervention ( n=9 ) or control ( n=8 ) group using a concealed method . INTERVENTION A 12-week arm-cranking exercise program , 3 sessions/wk , consisting of warming-up ( 10 - 15min ) followed by a main part in arm-crank ( 20 - 30min [ increasing 2min and 30s every 3wk ] ) at a moderate work intensity of 50 % to 65 % of the heart rate reserve ( starting at 50 % and increasing 5 % every 3 weeks ) and by a cooling-down period ( 5 - 10min ) . MAIN OUTCOME MEASURES Plasmatic levels of total antioxidant status as well as erythrocyte glutathione peroxidase activity were measured . Lipid and protein oxidation were determined as malondialdehyde and carbonyl group levels , respectively . Furthermore , physical fitness and body composition were assessed . RESULTS When compared with baseline results , maximum oxygen consumption was significantly increased ( P=.031 ) , suggesting an improvement in physical fitness in the intervention group . Regarding the antioxidant defense system , it was found that both total antioxidant status ( P=.014 ) and erythrocyte glutathione peroxidase activity ( P=.027 ) were significantly increased at the end of the training program . As a consequence , plasmatic levels of malondialdehyde ( P=.008 ) and carbonyl groups ( P=.022 ) were significantly reduced . CONCLUSION A 12-week arm-cranking exercise program improved the antioxidant defense system in adults with chronic SCI , which may finally attenuate both lipid and protein oxidation in this population Purpose Rheumatoid arthritis ( RA ) patients display high levels of oxidative stress . Transient exercise-induced increases in oxidative stress are thought to be adaptive in healthy population s. This study investigated the effect of exercise on markers of oxidative stress in RA , following acute exercise and a period of exercise training . Methods Acute exercise study : RA patients ( N = 12 , age : 56 ± 11 ) undertook a bout of exercise ( 30–40 min , 70 % VO2MAX ) , and blood sample s were taken before and after exercise to assess markers of oxidative stress . Training study : RA patients ( N = 19 , age : 56 ± 10 ) were r and omised into either a control or exercise group , who undertook 3 exercise sessions per week ( 30–40 min @70 % VO2MAX ) for 3 months . Plasma markers of oxidative stress ( protein carbonyls ( PC ) , lipid hydroperoxides ( LOOH ) , 3-nitrotyrosine ( 3-NT ) , total antioxidant capacity ( TAC ) and catalase ( CAT ) activity ) , inflammation ( interleukin-8 ( IL-8 ) and C-reactive protein ( CRP ) ) and nitric oxide metabolites ( NOx ) were assessed before and after training . Results Acute exercise study : Protein carbonyls ( PC ) ( + 18 % ) and NOx ( + 27 % ) were significantly increased following exercise . Training study : 3-nitrotyrosine ( 3-NT ) decreased ( 2.18 ± 1.78 to 1.10 ± 0.93 μM ) in the exercise group only , alongside increases in aerobic fitness ( 24.45 ± 4.98 to 27.10 ± 4.51 ml/kg/min−1 ) and reductions in disease activity score ( DAS : 3.47 ± 1.17 to 2.88 ± 0.76 ) . PC , LOOH , TAC , IL-8 , CRP and NOx concentrations , and CAT activity were unchanged in both groups . Conclusions Aerobic exercise training did not increase markers of oxidative stress in RA patients . 3-Nitrotyrosine and disease activity were decreased following exercise training Abstract Exercise can be an effective treatment for depression . Although the efficacy of exercise is well established , little is known concerning the biological changes associated with the antidepressant effects of exercise . A r and omized , controlled trial was conducted to evaluate the effects of adding exercise to the usual treatment on the thiobarbituric acid-reactive substances ( TBARS ) and brain-derived neurotrophic factor ( BDNF ) serum levels of severely depressed in patients . Twenty-six participants were r and omized to an exercise group ( n = 15 , exercise + treatment as usual ) or a control group ( n = 11 , treatment as usual ) . The participants in the exercise group completed a targeted dose of 16.5 kcal/kg/week of aerobic exercise , three times per week , throughout their hospitalizations . The control group did not exercise during their hospitalizations . The mean hospitalization length was of 21.63 ( 4.5 ) × 23.82 ( 5.7 ) days for exercise and control groups , respectively . The exercise group performed a median of nine sessions . After adjusting for previous tobacco use , a significant group × time interaction was found for TBARS serum levels ( p = 0.02 ) . A post hoc Bonferroni test revealed differences between the exercise and control groups at discharge . A significant time effect ( p < 0.001 ) but no group × time interaction was found ( p = 0.13 ) for BDNF serum levels . Adding exercise to the usual treatment of severely depressed in patients decreases the TBARS serum levels of severely depressed in patients after 3 weeks . Adding exercise had no additional effects on BDNF serum levels To determine the effects of continuous aerobic exercise training ( CON ) vs interval aerobic exercise training ( INT ) on glycemic control and endothelium-dependent vasodilatation , 43 participants with type 2 diabetes were r and omly allocated to the sedentary , CON , and INT groups . The CON and INT exercise training programs were design ed to yield the same energy expenditure/exercise session and included walking on treadmill for 30 and 40 min/day , 3 times/week for 12 weeks . Body fatness and heart rate at rest decreased and leg muscle strength increased ( all P < 0.05 ) in both the CON and INT groups . Fasting blood glucose levels decreased ( P < 0.05 ) in both exercise groups but glycosylated hemoglobin levels decreased ( P < 0.05 ) only in the INT group . Maximal aerobic capacity , flow-mediated dilation , and cutaneous reactive hyperemia increased significantly in both exercise groups ; however , the magnitude of improvements was greater in the INT group . Only the INT group experienced reductions in erythrocyte malondialdehyde and serum von Willebr and factor and increases in plasma glutathione peroxidase and nitric oxide ( all P < 0.05 ) . We concluded that both continuous and interval training were effective in improving glycemic control , aerobic fitness , and endothelium-dependent vasodilation , but the interval training program appears to confer greater improvements than the continuous training program The aim of the present study was to examine the effect of exercise training on adipokines , inflammatory markers , and oxidative stress in overweight children . Nineteen overweight children were r and omly assigned to an aerobic exercise training or sedentary control group for 8 weeks . Measurements included peak oxygen uptake ( V o(2)max ) , body weight and composition , adipokines ( C-reactive protein , interleukin 6 , tumor necrosis factor alpha , adiponectin , leptin , and resistin ) , and oxidative stress ( 8-isoprostane ) . There were no differences between groups for change in body weight or composition over the 8 weeks . Exercise training improved V o(2)max ( exercise group , 1.64 + /- 0.13 to 1.85 + /- 0.17L/min vs control group , 1.83 + /- 0.12 to 1.60 + /- 0.13 L/min , P < .05 ) but did not change any of the measured adipokines or the marker of systemic oxidative stress , 8-isoprostane . These data suggest that in the absence of weight loss , exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children This experimental study aim ed to determine the effects of the combined application of regular exercises and massage on the values of Malondialdehyde ( MDA ) , Nitric Oxide ( NOx ) , Glutathione ( GSH ) , Adenosine Deaminase ( ADA ) and Superoxide Dismutase ( SOD ) . Twenty five sedentary women ( 32 - 50 years ) who did not have the habit of getting regularly massages or exercising and participated voluntarily in the study . The subjects were r and omly separated into three groups : control group ( CG , n = 9 ) , exercise group ( EG , n = 8) , and massage and exercise group ( MEG , n = 8) . The basic result of this study was that a statistically significant decrease was observed in the post-test MDA values of both EG and MEG subjects . Moreover , when the GSH and SOD values are compared to CG , a statistically significant increase was determined in the values of both EG and MEG . As a result , the findings show that regular physical activities and massage manipulations significantly decrease MDA , increase SOD and GSH activities , and result in no change in NOx and ADA activities supports the assumption that regular physical activity has positive health effects OBJECTIVE To compare exercise-induced oxidative stress and levels of homocysteine and cholesterol in normal-weight and overweight older adults after resistance exercise ( RX ) . RESEARCH METHODS AND PROCEDURES This interventional study was conducted at a wellness center . Forty-nine older adults ( age range , 60 to 72 years ) were stratified by BMI ( < 25 kg/m(2 ) normal weight , > or = 25 kg/m(2 ) overweight/obese ) and then r and omly assigned to either a control non-exercise group or an RX group . The RX group completed a 6-month training program . Exercise-induced lipid hydroperoxides ( PEROXs ) and thiobarbituric-reactive acid substances , homocysteine , lipoprotein a , cholesterol , and high-density lipoprotein cholesterol were measured before and after the 6-month RX program . RESULTS PEROXs and thiobarbituric-reactive acid substances were lower in both the overweight/obese and normal-weight RX-trained groups compared with control groups ( p < 0.05 ) . Homocysteine levels were lower in both overweight/obese and normal-weight RX groups compared with control groups ( p < 0.05 ) . Lipoprotein a , total cholesterol , and high-density lipoprotein cholesterol were not different in normal-weight and overweight/obese groups before or after RX . The change in muscle strength was correlated with homocysteine at 6 months ( r = -0.452 , p < 0.05 ) , whereas the change in PEROXs was correlated with the change in body fat ( r = -0.329 ) . DISCUSSION To our knowledge , these data are the first to show that RX reduces exercise-induced oxidative stress and homocysteine regardless of adiposity , indicating that this protection can be afforded in an older , overweight/obese population as effectively as in healthy older adults . These data suggest that RX may afford some protection against emerging cardiovascular risk factors using a mode of exercise that supports body weight BACKGROUND Heart transplantation normalizes central hemodynamics , but endothelial dysfunction persists after transplantation . METHODS To investigate the effects of aerobic exercise on arterial function , oxidative stress , lipid profile , and sympathetic nervous system activity , 20 heart transplant recipients ( age , 54.3 + /- 9.1 years ; 17 men , 3 women ) were r and omly assigned to 12 weeks of supervised treadmill exercise ( Trained ; n = 10 ) or st and ard medical care ( Control ; n = 10 ) . Supervised exercise was initiated at 8 weeks after transplant . Brachial artery reactivity was assessed using flow-mediated dilation . RESULTS The VO2 peak increased 26 % in the Trained patients ( 15.4 + /- 4.3 vs 19.4 + /- 5.5 ml/kg/min ; p < or = 0.05 ) but did not change in the Controls ( 16.2 + /- 5.2 vs 16.8 + /- 2.8 ml/kg/min ; p > or = 0.05 ) . Brachial artery flow-mediated dilation ( 10.1 % + /- 6.1 % vs 9.6 % + /- 6.2 % ) and absolute brachial diameter ( 0.48 + /- 0.22 vs 0.42 + /- 0.24 mm ) did not change in Trained patients , but brachial flow-mediated dilation ( 10.5 % + /- 2.8 % vs 7.9 % + /- 5.1 % ) and the absolute change in brachial diameter ( 0.48 + /- 0.16 vs 0.36 + /- 0.24 mm ) decreased significantly ( p < or = 0.05 ) in the Control patients . Resting norepinephrine decreased significantly ( p < or = 0.05 ) after training ( 0.32 + /- 0.19 vs 0.22 + /- 0.22 ng/ml ) , but there was a nonsignificant trend toward increased norepinephrine in the Controls ( 0.26 + /- 0.17 vs 0.53 + /- 0.41 ng/ml ; p = 0.07 ) . The lipid profile and marker of oxidative stress did not differ between the groups before or after the intervention . CONCLUSIONS To our knowledge , this is the first prospect i ve , r and omized study to investigate the effects of heart transplantation and aerobic exercise on peripheral artery function in the same cohort of heart transplant recipients . Brachial artery flow-mediated dilation increased early in the post-operative period . Aerobic exercise preserved but did not improve brachial artery flow-mediated dilation . Heart transplant recipients who did not participate in supervised exercise showed a progressive decline in brachial artery flow-mediated dilation Background Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus . This study investigated the impact of Hatha yoga and conventional physical training ( PT ) exercise regimens on biochemical , oxidative stress indicators and oxidant status in patients with type 2 diabetes . Methods This prospect i ve r and omized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups . Biochemical parameters such as fasting blood glucose ( FBG ) , serum total cholesterol ( TC ) , triglycerides , low-density lipoprotein ( LDL ) , very low-density lipoproteins ( VLDL ) and high-density lipoprotein ( HDL ) were determined at baseline and at two consecutive three monthly intervals . The oxidative stress indicators ( malondialdehyde – MDA , protein oxidation – POX , phospholipase A2 – PLA2 activity ) and oxidative status [ superoxide dismutase ( SOD ) and catalase activities ] were measured . Results The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48 % and 27.43 % respectively ( P < 0.0001 ) and there was a significant reduction in serum TC in both groups ( P < 0.0001 ) . The concentrations of VLDL in the managed groups after six months differed significantly from baseline values ( P = 0.036 ) . Lipid peroxidation as indicated by MDA significantly decreased by 19.9 % and 18.1 % in the Hatha yoga and conventional PT exercise groups respectively ( P < 0.0001 ) ; whilst the activity of SOD significantly increased by 24.08 % and 20.18 % respectively ( P = 0.031 ) . There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68 % and 13.19 % in the Hatha yoga and conventional PT exercise groups respectively ( P = 0.144 ) . Conclusion The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose , lipid profile , oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status . Trial Registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) : OBJECTIVE To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength , bone mineral density ( BMD ) , structural joint damage , and on disease activity in patients with early rheumatoid arthritis ( RA ) . METHODS Seventy patients were r and omised either to perform home based strength training with loads of 50 - 70 % of repetition maximum ( EG ) or range of motion exercises ( CG ) . Both groups were encouraged to take part in aerobic activities 2 - 3 times a week . Maximal muscle strength of different muscle groups was measured by dynamometers , and BMD at the femoral neck and lumbar spine by dual x ray densitometry . Disease activity was assessed by the 28 joint disease activity score , and joint damage by x ray findings . RESULTS 62 patients completed 2 years ' training and 59 patients attended check up at 5 years . Mean ( SD ) maximum muscle strength indices increased from baseline to 2 years-in EG from 212 ( 78 ) kg by a mean ( 95 % CI ) of 68 ( 55 to 80 ) and in CG from 195 ( 72 ) kg by 35 ( 13 to 60 ) kg- and remained at that level for the next 3 years . Development of BMD in EG tended to be more favourable than that in CG . Muscle strength training was not detrimental to joint structures or disease activity . CONCLUSION The patients ' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years . Despite substantial training effects in muscle strength , BMD values remained relatively constant . Radiographic damage remained low even at 5 years PURPOSE Aging is associated with increased oxidative stress , whereas systematic exercise training has been shown to improve quality of life and functional performance of the aged . This study aim ed to evaluate responses of selected markers of oxidative stress and antioxidant status in inactive older men during endurance training and detraining . METHODS Nineteen older men ( 65 - 78 yr ) were r and omly assigned into either a control ( C , N = 8) or an endurance-training ( ET , N = 11 , three training sessions per week , 16 wk , walking/jogging at 50 - 80 % of HR(max ) ) group . Before , immediately posttraining , and after 4 months of detraining , subjects performed a progressive diagnostic treadmill test to exhaustion ( GXT ) . Plasma sample s , collected before and immediately post-GXT , were analyzed for malondialdehyde ( MDA ) and 3-nitrotyrosine ( 3-NT ) levels , total antioxidant capacity ( TAC ) , and glutathione peroxidase activity ( GPX ) . RESULTS ET caused a 40 % increase in running time and a 20 % increase in maximal oxygen consumption ( VO(2max ) ) ( P < 0.05 ) . ET lowered MDA ( 9 % at rest , P < 0.01 ; and 16 % postexercise , P < 0.05 ) and 3-NT levels ( 20 % postexercise , P < 0.05 ) , whereas it increased TAC ( 6 % at rest , P < 0.01 ; and 14 % postexercise , P < 0.05 ) and GPX ( 12 % postexercise , P < 0.05 ) . However , detraining abolished these adaptations . CONCLUSIONS ET may attenuate basal and exercise-induced lipid peroxidation and increase protection against oxidative stress by increasing TAC and GPX activity . However , training cessation may reverse these training-induced adaptations Background —In chronic heart failure ( CHF ) , cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle ( SM ) . The role of the radical scavenger enzymes superoxide dismutase ( SOD ) , catalase ( Cat ) , and glutathione peroxidase ( GPX ) , which remove oxygen radicals , has never been assessed in the SM in this context . Moreover , it remains unknown whether exercise training augments the activity of these enzymes in CHF . Methods and Results —Twenty-three patients with CHF were r and omized to either 6 months of exercise training ( T ) or a sedentary lifestyle ( C ) ; 12 age-matched healthy subjects ( HS ) were studied in parallel . Activity of Cat , SOD , and GPX was assessed in SM biopsies before and after 6 months ( 6 months ) . Oxidative stress was determined by measuring nitrotyrosine formation . SOD , Cat , and GPX activity was reduced by 31 % , 57 % , and 51 % , respectively , whereas nitrotyrosine formation was increased by 107 % in SM in CHF ( P<0.05 versus HS ) . In CHF , exercise training augmented GPX and Cat activity in SM by 41 % ( P<0.05 versus before and group C ) and 42 % ( P<0.05 versus before and group C ) , respectively , and decreased nitrotyrosine production by 35 % ( from 3.8±0.4 % tissue area before to 2.5±0.3 % after 6 months ; P<0.05 versus before ) . Conclusions —The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress . Exercise training exerts antioxidative effects in the SM in CHF , in particular , due to an augmentation in activity of radical scavenger enzymes This study was aim ed at investigating the effects of a 21-week period of progressive strength or endurance training on peripheral blood mononuclear cells ( P BMC ) antioxidant enzyme gene expression and activity in healthy middle-aged untrained men . Strength ( n=11 ) and endurance ( n=12 ) training were performed twice a week , including resistance exercises to activate all the main muscle groups or cycle-ergometer pedaling , respectively . mRNA levels of catalase , glutathione peroxidase ( GPx ) , mitochondrial superoxide dismutase ( MnSOD ) and cytosolic superoxide dismutase ( CuZnSOD ) were increased after 21 weeks of strength training , while endurance training induced significant changes only in MnSOD and GPx mRNA levels . CuZnSOD protein content was significantly increased only in strength-trained subjects . The program of strength or endurance exercise training had no significant effects on the activity of any of the antioxidant enzymes . In conclusion , in a middle-aged population , 21 weeks of strength or endurance training was a sufficient stimulus to up-regulate mRNA levels of P BMC antioxidant enzymes , the strength training being a more optimal stimulus . However , the discrepancies between enzyme protein and mRNA levels suggest that the present systematic strength or endurance training period had no beneficial effects on enzymatic antioxidant defense mechanisms in previously untrained middle-aged men 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 Scientific evidence from different sources suggests a positive association between sedentary behaviors and the incidence of hypertension . However , no previous prospect i ve study corroborated this potential relationship in an adult population . Our objective was to assess prospect ively the association of different sedentary behaviors ( interactive and noninteractive sedentary activity , television viewing , and sleeping ) with the incidence of hypertension . METHODS In this prospect i ve , dynamic cohort study ( the SUN Study ) , 11,837 Spanish university graduates , with a mean age of 36 years , were followed for an average of 40 months , from 1999 to 2006 . Sedentary behavior was assessed with a question naire at baseline , and the incidence of hypertension was assessed with vali date d , biennial question naires . RESULTS We identified 291 new cases of hypertension among 6742 participants who remained after excluding those with self-reported hypertension , cardiovascular disease , diabetes , and cancer at baseline . Self-reported total sedentary behavior was directly associated with a higher risk of hypertension ( hazard ratio , 1.48 ; 95 % confidence interval , 1.01 to 2.18 , comparing those in the upper and lower quartiles ; P for trend = .03 ) . In subtype analyses , interactive sedentary behavior ( driving and computer use ) , but not noninteractive sedentary behavior ( television viewing and sleeping ) , was associated with a higher risk of hypertension . CONCLUSIONS Interactive sedentary behaviors appear to be an independent risk factor for incident hypertension . Noninteractive sedentary behaviors ( television viewing and sleeping ) did not show a significant association with incident hypertension UNLABELLED Oxidative stress seems to be involved in the pathogenesis of Parkinson disease ( PD ) . Exercise training can increase endogenous antioxidant protection and decrease the production of reactive oxygen and nitrogen species . PURPOSE To investigate the effect of exercise training on oxidative status in persons with PD . METHODS Sixteen subjects with PD were match-r and omly assigned to resistance exercise ( n = 8) or a no-exercise control group ( n = 8) on the basis of disease stage ( Hoehn and Yahr stages I and II ) and sex . Supervised exercise was performed twice weekly for 8 wk , consisting of three sets each of the leg press , leg curl , and calf press . Resting blood sample s were taken from subjects before and after the intervention and assayed for markers of oxidative stress [ malondialdehyde ( MDA ) and hydrogen peroxide ( H2O2 ) ] and antioxidant capacity ( superoxide dismutase , catalase , glutathione peroxidase , and trolox-equivalent antioxidant capacity ) . RESULTS The exercise program was well-tolerated and associated with modest trends toward decreased oxidative stress and increased antioxidant capacity . The two biomarkers of oxidative stress were decreased after exercise training [ MDA ( 15 % ) and H2O2 ( 16 % ) ] . With these changes , a postintervention difference was apparent between the resistance exercise training and control groups for H2O2 ( P = 0.007 ) , with a trend for difference noted for MDA ( P = 0.06 ) . The mean increases in superoxide dismutase ( 9 % ) and glutathione peroxidase ( 15 % ) noted in the exercise training group were not statistically significant ( P > 0.05 ) . CONCLUSIONS Short-term resistance training may be associated with reduced oxidative stress in subjects with PD . Future studies with larger sample s , inclusive of a higher volume of resistance exercise , are needed to extend these findings Objectives . Our aim was to determine the effect of chronic regular exercise on ischemia-modified albumin ( IMA ) levels and oxidative stress in type 2 diabetes mellitus ( DM ) . Design and methods . Sixty patients with type 2 DM were r and omly divided into two groups as exercise ( 17 M , 13 F ) and non-exercise ( 12 M , 18 F ) groups , each consisting of 30 patients . The exercise group underwent a 3-month aerobic regular exercise consisting of moderate-intensity power walking . The non-exercise subjects remained sedentary throughout the study period . Serum total antioxidant status ( TAS ) , total oxidant status ( TOS ) , and IMA levels of the groups were determined at baseline and 3 months later . Results . There was no significant change in TOS and IMA levels of exercise group but TAS levels were significantly increased ( p < 0.05 ) . Also , postexercise systolic ( p < 0.001 ) and diastolic ( p < 0.05 ) blood pressures of the exercise group were significantly lower than the baseline values . In addition , there was no significant change in TAS and TOS levels of the non-exercise group ; however , IMA levels were significantly increased ( p < 0.01 ) . Conclusion . We have shown , for the first time , that exercise prevents increase in IMA levels in type 2 DM which might have result ed from increased levels of TAS and reduces the risk of ischemia in these patients . These findings show that chronic exercise is beneficial in the prevention of oxidative stress in patients with type 2 DM as documented by decreased IMA levels The objective of this study was to investigate the effects of 12 weeks of st and ard cardiac rehabilitation on endothelial function , oxidative stress , and antioxidant defenses in patients with coronary artery disease . Twelve weeks of endurance exercise training led to an improvement in endothelial function as measured by brachial artery flow-mediated dilation ( 7.9 % at baseline vs 11.1 % at 12 weeks ) . Exercise training result ed in increased plasma nitrite and nitrate levels , increased plasma superoxide dismutase activity , and decreased oxidative stress BACKGROUND This study aim ed to determine whether oxidative stress was related to cardiovascular risk indices in children , and whether an exercise intervention would reduce oxidative stress . METHODS A r and omized trial of two different doses of exercise and a no-exercise control group included 112 overweight and obese children , 7 - 11 years old . Plasma isoprostane levels were obtained at baseline and after the intervention . Cross-sectional analysis of oxidative stress and metabolic markers at baseline was performed . The effect of the exercise training on oxidative stress was tested . RESULTS Lower isoprostane levels were observed in blacks . At baseline , isoprostane was positively related to measures of fatness ( BMI , waist circumference , percent body fat ) , insulin resistance and β-cell function ( fasting insulin , insulin area under the curve , Matsuda index , disposition index , oral disposition index ) , and several lipid markers ( low-density lipoprotein , triglycerides , total cholesterol ) , and inversely with fitness [ peak oxygen consumption ( VO(2 ) ) ] , independent of race , sex , and cohort . No relation was found with visceral fat , blood pressure , or glycemia . Independent of percent body fat , isoprostane predicted triglycerides , β=0.23 , total cholesterol-to-high-density lipoprotein ( TC/HDL ) ratio , β=0.23 , and insulin resistance ( insulin area under the curve , β=0.24 , Matsuda index , β=-0.21 , oral disposition index , β=0.33 ) . Exercise did not reduce oxidative stress levels , despite reduced fatness and improved fitness in these children . CONCLUSIONS Isoprostane levels were related to several markers of cardiovascular risk at baseline ; however , despite reduced fatness and improved fitness , no effect of exercise was observed on isoprostane levels . To our knowledge , this is the first report in children to demonstrate a correlation of oxidative stress with disposition index , fitness , and TC/HDL ratio , the first to test the effect on oxidative stress of an exercise intervention that reduced body fat , and the first such exercise intervention study to include a substantial proportion of black children Background : We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease . Methods and results : A r and omized , controlled trial was conducted to determine the effects of an 8-week exercise training programme ( n = 32 ) vs. controls ( n = 32 ) on brachial flow-mediated dilation ( FMD ) in patients with stable CAD . After 8 weeks , patients received exercise training had significant improvements in FMD ( 1.84 % , p = 0.002 ) and exercise capacity ( 2.04 metabolic equivalents , p < 0.001 ) compared with controls . The change in FMD correlated inversely with baseline FMD ( r = −0.41 , p = 0.001 ) and positively with the increase in exercise capacity ( r = 0.35 , p = 0.005 ) . After adjusting for confounders , every 1 metabolic equivalent increase in exercise capacity was associated with 0.55 % increase in FMD . Furthermore , patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls . However , exercise training did not alter high-sensitivity C-reactive protein , oxidative stress measured as superoxide dismutase and 8-isoprostane , and CD34/KDR + endothelial progenitor cell count . Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity ( < median value of 7.65 metabolic equivalents , p = 0.004 ) but not in those with normal exercise capacity . Conclusion : Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation , oxidative stress , or endothelial progenitor cells . The beneficial effects of exercise training on FMD and exercise capacity are inter-related , and more pronounced in those with baseline impaired exercise capacity |
11,284 | 29,763,500 | Regardless of the material used for regeneration , different degrees of graft resorption should be expected .
Given the sample of investigations analyzed in this review , block grafts seemed to maintain the volume of the initial augmentation site more than GBR techniques .
During the initial stages of healing , the GBR technique experienced more changes compared with block grafts .
The resorption of the xenograft group was inferior compared with the combination of xenograft and autologous bone groups . | PURPOSE Owing to volumetric changes after tooth extraction , lateral ridge augmentation has become a common procedure prior or simultaneous to implant placement .
Nonetheless , little is known with regard to the dimensional remodeling after healing of these lateral ridge augmentation procedures .
Hence , the purpose of this systematic review was to assess the stability of bone grafting material between augmentation procedures and final healing , in terms of resorption rate . | OBJECTIVES The aim of this r and omized , controlled clinical trial was to compare the potential of a synthetic bone substitute or a bovine-derived xenograft combined with a collagen membrane to preserve the alveolar ridge dimensions following tooth extraction . METHODS Twenty-seven patients were r and omized into two treatment groups following single tooth extraction in the incisor , canine and premolar area . In the test group , the alveolar socket was grafted with Straumann Bone Ceramic ( SBC ) , while in the control group , Bio-Oss deproteinized bovine bone mineral ( DBBM ) was applied . In both groups , a collagen barrier was used to cover the grafting material . Complete soft tissue coverage of the barriers was not achieved . After 8 months , during re-entry procedures and before implant placement , the horizontal and vertical dimensions of the residual ridge were re-evaluated and trephine biopsies were performed for histological analysis in all patients . RESULTS Twenty-six patients completed the study . The bucco-lingual dimension of the alveolar ridge decreased by 1.1+/-1 mm in the SBC group and by 2.1+/-1 in the DBBM group ( P<0.05 ) . Both material s preserved the mesio-distal bone height of the ridge . No differences in the width of buccal and palatal bone plate were observed between the two groups . The histological analysis showed new bone formation in the apical part of the biopsies , which , in some instances , was in direct contact with both SBC and DBBM particles . The coronal part of the biopsies was occupied by a dense fibrous connective tissue surrounding the SBC and DBBM particles . CONCLUSION Both bio material s partially preserved the width and the interproximal bone height of the alveolar ridge PURPOSE This prospect i ve case series evaluated the use of a new titanium-reinforced nonresorbable membrane ( high-density polytetrafluoroethylene ) , in combination with a mixture of anorganic bovine bone-derived mineral ( ABBM ) and autogenous particulated bone , for vertical augmentation of deficient alveolar ridges . MATERIAL S AND METHODS A mixture of ABBM and autogenous particulated bone was used for vertical ridge augmentation and covered with a new titanium-reinforced nonresorbable membrane . Ridge measurements were obtained before and after the procedure , complications were recorded , and biopsy specimens were taken for histologic examination . RESULTS Twenty vertical ridge augmentation procedures were carried out in 19 patients . All treated defect sites exhibited excellent bone formation , with an average bone gain of 5.45 mm ( st and ard deviation 1.93 mm ) . The healing period was uneventful , and no complications were observed . Eight specimens were examined histologically ; on average , autogenous or regenerated bone represented 36.6 % of the specimens , ABBM 16.6 % , and marrow space 46.8 % . No inflammatory responses or foreign-body reactions were noted in the specimens . CONCLUSION The treatment of vertically deficient alveolar ridges with guided bone regeneration using a mixture of autogenous bone and ABBM and a new titanium-reinforced nonresorbable membrane can be considered successful OBJECTIVES S and wich bone augmentation ( SBA ) has been proposed to augment the width of edentulous ridges for implant placement . This study aim ed to investigate the effect of a membrane on SBA for the regeneration of buccal implant dehiscence defects . MATERIAL AND METHODS Twenty-six healthy patients , each with a single defect , were r and omly assigned into two groups . Both groups received an inner and outer layer of mineralized human cancellous and cortical particulate allograft . In the test group , a bovine pericardium membrane covered the bone grafts , while no membrane was placed in the control group . Cone beam computed tomography ( CBCT ) scans were taken before and immediately after implant placement and at 6 months post-surgery . RESULTS All implants placed were successfully osseointegrated at 6 months . Clinical re-entry measurements showed significant buccal bone gain in the test group compared with the control group ( P < 0.05 ) . The test group had 1.12 , 2.21 and 2.44 mm more buccal bone thickness at 2 , 4 and 6 mm below the bone crest . There were no significant differences in the mid-buccal vertical bone height , defect height and width reductions and bone fill between the two groups ( P > 0.05 ) . Cone beam computed tomography analysis demonstrated significant buccal bone gain of 1.22 mm in the test group . Radiographic vertical bone loss at 1-year post-surgery showed no significant differences between the groups . CONCLUSION S and wich bone augmentation is a predictable technique for regenerating buccal bone on implant dehiscence defects . Addition of a barrier membrane prevented significant horizontal buccal bone resorption as space was maintained more effectively when compared with sites treated without a membrane Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Background and Purpose : The resorption of alveolar bone following tooth extraction results in a narrowing and shortening of the residual ridge , which leads to esthetic and restorative problems , and reduces the bone volume available for implant therapy . The aim of this study was to evaluate the prevention of alveolar collapse after tooth extraction , using titanium membrane ( Frios Boneshield ; DENTSPLY Friadent , Mannheim , Germany ) , associated ( or not ) with autologous bone graft . Material s and Methods : A total of 10 nonsmoking healthy subjects , ranging from 35 to 60 years old , were selected for this study . Each patient had a minimum of 2 uni-radicular periodontally hopeless teeth , which were scheduled for extraction . After the procedure , 2 titanium pins were fixed on the vestibular bone surfaces that were used as references for the initial measures ( depth , width , and height ) of the socket . Of the sockets,1 was r and omly chosen to be filled with autologous bone graft ( test ) removed from superior maxillary tuber , and the other one did not receive the graft ( control ) . A titanium membrane was adapted and fixed , covering the sockets , which remained for at least 10 weeks . After a 6-month healing , the final measures were performed . Results : There was exposure of the membrane in 5 of the 10 treated subjects . Average bone filling ( ±st and ard deviation ) among the 10 subjects was 8.80 ± 2.93 mm ( range 4 - 13 ) in the control group and 8.40 ± 3.35 mm ( range 4 - 13 ) in the test group . Average bone loss in width in both group was 1.40 ± 1.97 mm ( range −4 - 1 ) in the control group and 1.40 ± 0.98 mm ( range −4 - 0 ) in the test group . There was no significant statistical difference between groups considering the evaluated st and ards . Conclusion : The use of titanium membrane , alone or in association with autogenous bone , favored the prevention of alveolar ridge after tooth extraction . This membrane seems to be a possible and safe alternative to other nonresorbable membranes when the prevention of alveolar ridge resorption is the objective OBJECTIVES This study was conducted to evaluate the effect of barrier membranes on s and wich bone augmentation ( SBA ) for the treatment of implant dehiscence defects . MATERIAL AND METHODS Twenty-six implant-associated buccal dehiscence defects in 22 patients were treated according to the SBA concept - mineralized human cancellous allograft ( inner layer ) , mineralized human cortical allograft ( outer layer ) and coverage with barrier membrane . The defects were r and omly assigned to the bovine collagen membrane ( BME ) group ; acellular dermal matrix ( ADM ) group ; and no membrane group . Measurements at baseline and 6 months re-entry included defect height ( DH : from smooth-rough junction to the most apical part of the defect ) , defect width ( DW : at the widest part of the defect ) , and horizontal defect depth ( HDD : at three locations - smooth-rough junction , middle , and most apical portion of the defect ) . All measurements were taken from a reference stent . Statistical analyses were performed for comparison of intra- and inter-group comparisons . RESULTS All implants placed were successfully osseointegrated . DH at baseline for three groups were not significantly different ( P=0.858 ) . Mean % DH reductions for ADM , BME , and control groups at 6 months were 73.9+/-17.6 % , 68.1+/-30.1 % , and 63.6+/-23.9 % , respectively , with no significant difference among the groups ( P=0.686 ) . Mean horizontal bone gain , however , was significantly greater for membrane groups ( 1.7 mm for ADM , 1.6 mm for BME ) compared with control group ( 1 mm ) ( P=0.044 ) . Implant exposure result ed in significant reduction in total height gain ( 79.1+/-14.3 % vs. 57+/-23.5 % , P=0.021 ) . CONCLUSIONS Within the limit of this study , it is concluded that SBA technique achieved predictable clinical outcomes . The addition of absorbable membranes enhanced bone gain in thickness compared with membrane-treated sites BACKGROUND Platelet-rich plasma ( PRP ) contains a number of biologically active growth factors , and previous studies have reported conflicting ridge augmentation results . The primary aim of this r and omized , controlled , masked , clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP . METHODS Thirty-two patients with an edentulous ridge defect were sequentially entered into the study ; four were excluded from data analysis . Fourteen patients received a cancellous allograft ( CAN group ) and the other 14 received a cancellous allograft mixed with PRP ( PRP group ) . All 28 grafted sites were covered with a resorbable polylactide membrane . After elevation of a full-thickness flap , horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest . Vertical ridge dimensions were measured from a tooth-supported stent . All sites were reentered at 4 months , and a trephine core was obtained for histologic analysis before implant placement . RESULTS The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm , whereas the PRP group gained 2.9 ± 1.0 , and the difference was statistically significant between groups ( P < 0.05 ) . The percent vital bone was 36 % ± 14 % for the CAN group compared with 51 % ± 15 % for the PRP group and was statistically significant between groups ( P < 0.05 ) . Loss of augmented ridge width was 34 % ± 17 % for the CAN group and 28 % ± 17 % for the PRP group ( P > 0.05 ) . CONCLUSION These clinical and histologic findings suggest that PRP enhanced bone regeneration and result ed in increased horizontal bone gain and percentage vital bone One of the key factors for attaining osseointegration is the presence of an adequate osseous volume . In patients with inadequate osseous width or height , a bone augmentation using the guided bone regeneration ( GBR ) concept may be applied either with a simultaneous or a staged approach . The aim of this multicenter prospect i ve case series study was to evaluate the efficacy and predictability of the GBR technique ( simultaneous approach ) in patients with peri-implant osseous defects , both dehiscences and fenestrations . Results 5 years post-treatment ( survival rates and marginal bone level ) were assessed . A total of 19 consecutive patients with 26 peri-implant osseous defects ( 20 dehiscences and six fenestrations ) were treated during the period from September 1992 to June 1993 with a simultaneous GBR approach using non-resorbable membranes combined with autogenous bone grafts or decalcified freeze-dried bone allograft . The mean osseous augmentation was 94.8 % . Marginal bone levels at re-entry and 5 years after surgery were calculated from st and ardized periapical radiographs . One implant was lost 3 months after loading . Thus , the cumulative survival rate was 96.1 % after 5 years . The mean marginal bone level after 5 years was 2.03 mm ( SD=+/-0.5 ) , without a difference between mesial and distal sites . This study demonstrates that implants with peri-implant defects that are treated with GBR had similar survival rates and crestal bone levels compared with implants in native bone PURPOSE In the present prospect i ve study , bone augmentation by guided bone regeneration ( GBR ) in combination with bovine hydroxyapatite ( BHA ) as filling material was evaluated with regard to soft and hard tissue stability over time . MATERIAL S AND METHODS Implant survival , radiologic bone level ( marginal bone level [ MBL ] ) , and clinical soft tissue parameters ( marginal soft tissue level [ MSTL ] ) were observed . Twenty patients received a total of 41 implants ( Brånemark System , Nobel Biocare , Göteborg , Sweden ) in conjunction with GBR treatment . The end point of the study was after 5 years following implant placement . RESULTS The cumulative implant survival rate was 97.5 % corresponding to one implant failure . The radiologic evaluation of the MBL demonstrated a crestal bone height above the level of the fixture head . The bone height decreased from -3.51 to -2.38 mm ( p < .001 ) . The MSTL was -1.52 mm at baseline and -1.15 mm at the 5-year follow-up ( p < .04 ) demonstrating a stable submucosal crown margin throughout the study period . CONCLUSION GBR treatment in combination with a xenogeneic filling material ( BHA ) is a viable treatment option in order to maintain stable hard and soft tissue levels in conjunction with augmentative procedure related to oral implant treatment AIM To compare the effect of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) in an absorbable collagen sponge carrier ( ACS ) with autogenous bone graft for augmentation of the edentulous atrophic anterior maxilla . METHODS Twenty-four subjects were enrolled in a r and omized , controlled , parallel-group , open-label clinical trial . Subjects either received rhBMP-2/ACS ( 1.5 mg/ml ) or particulated autogenous bone harvested from the m and ibular retromolar region . A titanium-mesh was used to provide space and wound stability . A guide was used to st and ardize clinical recordings using an analogue caliper . Alveolar ridge width was also assessed using cone-beam computed tomography . RESULTS rhBMP-2/ACS yielded significantly greater radiographic horizontal bone gain compared with autogenous bone graft at immediate subcrestal levels ( 1.5 ± 0.7 versus 0.5 ± 0.9 mm ; p = 0.01 ) ; non-significant differences were observed at mid- ( 2.9 ± 0.8 versus 2.9 ± 0.9 mm ; p = 0.98 ) and apical ( 1.7 ± 0.9 versus 1.8 ± 1.1 mm ; p = 0.85 ) crestal levels . No significant differences in clinical horizontal bone gain were observed at 6 months between rhBMP-2/ACS and autogenous bone graft ( 3.2 ± 0.9 mm versus 3.7 ± 1.4 mm ; p = 0.31 ) . Sixty-two implants were placed after 6 month of healing with no significant differences between groups for number of implants , implant size , primary stability and survival . CONCLUSIONS rhBMP-2/ACS appears a realistic alternative for augmentation of the edentulous atrophic anterior maxilla PURPOSE The aim of this r and omized clinical trial was to compare the potential of deproteinized bovine bone added to autologous bone or corticocancellous allograft block with or without the addition of recombinant human platelet-derived growth factor-BB ( rhPDGF-BB ) to regenerate m and ibular atrophic ridges . MATERIAL S AND METHODS TRIAL DESIGN parallel , allocation ratio of 1:1 using a split-mouth model . Eligibility criteria for patients : adult patients ; bilateral atrophic edentulous areas in the posterior area of the m and ible ; a preoperatory cone beam computed tomography scan ; and absence of systemic diseases affecting the bone metabolism . Bone graft intervention for control group consisted of bone chips collected with a scraper mixed with deproteinized bovine bone covered with a resorbable membrane . Bone graft intervention for test group consisted of a corticocancellous allograft block , shaped before surgery , and protected with a collagen membrane . In addition , both groups received rhPDGF-BB or a saline solution as control . As primary outcome quantity , bone variation after a 1-year healing period was considered . A p-value of.05 was considered statistically significant . RESULTS Sixteen patients were enrolled in this trial . A total of 50 implants and 32 bone grafts were placed . All patients concluded the study ( no dropouts ) . Change at 1 year in bone volume was not significantly different between the two groups ( p-value = .25 ) . Effect of treatment in terms of change in bone volume at 1 year was not significant ( p-value = .89 ) when saline solution was used while was at limit of significance when rhPDGF-BB was used ( p-value = .052 ) . After 1 year , all the implants were successfully integrated . CONCLUSIONS The block allograft and the st and ard regenerative procedure showed similar results in terms of regenerated bone volume after 1 year of functional loading . The rhPDGF-BB positively influenced soft-tissue healing PURPOSE The aim of this r and omised controlled double-blinded clinical trial was to determine the efficacy of a new cross-linked membrane ( VN ) in guided bone regeneration ( GBR ) around exposed dental implants compared to a native collagen membrane ( BG ) . MATERIAL AND METHODS A total of 16 patients in need of implant treatment at two different sites with osseous defects were planned for this split-mouth study . After inserting the dental implants , peri-implant defects were treated according to the GBR technique using a VN membrane with prolonged resorption time in the r and omised test site and a BG membrane in the control site . After a healing time of 6 months , mucoperiosteal flaps were elevated for the evaluation of the primary ( vertical bone fill [ ΔDL ] and quality of newly formed tissue [ QT ] ) and secondary outcome variables ( infrabony defect height [ DH ] , defect width [ DW ] , defect depth [ DD ] and augmentation depth [ AD ] ) and the sampling of biopsies apical to the implant shoulder . RESULTS A total of 16 patients fulfilled the initial non-surgical inclusion and exclusion criteria . However , the study was discontinued early after 9 surgically treated patients because unacceptable safety issues arose and severe infection related to the VN membranes . The VN membrane revealed statistically significantly more soft tissue dehiscence than the BG membrane ( 56 % and 11 % , respectively , P = 0.0455 ) . In 3 of these 9 patients the VN membrane had to be removed due to infection early after the first follow-up visit . For the statistical analyses these sites were design ated as the value of the baseline . The mean ΔDL values were 1.8 ± 1.6 mm at the VN site and 4.7 ± 3.3 mm at the BG site . The ΔDD values were 0.6 ± 1.0 mm and 1.1 ± 1.2 mm , respectively , and reached statistical significance ( P = 0.0208 , CI 95 % = -2.9 [ -5.2;-0.6 ] ) . The corresponding linear defect fill ( DF ) values were 44 % and 78 % , respectively . The clinical assessment of QT showed comparable median values at sites treated with VN ( 3 , interquartile range : 0 ; 3.5 ) and BG ( 3 , interquartile range : 3 ; 4 ) without statistical significance . The histomorphometric analysis showed an average area density of 24.4 % ( SD 10.3 , range 8 - 35 % ) newly formed bone at the test sites and of 35.0 % ( SD 20.6 , range 8 - 60 % ) at the control sites . The histological data showed only some trends and did not reach statistical significance . CONCLUSION In the present study , the VN membranes with prolonged resorption time demonstrated significantly more adverse events and insufficient bone regeneration compared to the native BG membranes and no advantages in favour of the VN membranes were detectable PURPOSE To evaluate the outcome of intraoral soft tissue expansion by measuring the profile change using objective 3D metering equipment and to evaluate localized bone grafting after soft tissue expansion with regard to gain of bone and complications . MATERIAL S AND METHODS Using a prospect i ve study design , we asked patients with an osseous and soft tissue defect on the buccal aspect of the alveolar process to participate in this study . In 10 patients ( experimental group ) a self-inflatable soft tissue exp and er was placed under the periosteum . After 2 weeks , the exp and er was removed and a particulated onlay bone graft was placed in the exp and ed area , protected by a titanium mesh covered with a collagen membrane . Ten patients ( reference group ) were treated with a m and ibular ramus bone block graft . The soft tissue profile was registered before each surgical procedure . The vertical and lateral dimensions of the bone grafts were noted at the grafting procedure and at the implant installation . P < .05 was considered significant . RESULTS The mean soft tissue profile change was 2.9 ± 1.1 mm after soft tissue expansion and 2.3 ± 2.1 mm at implant placement in the experimental group compared with 1.5 ± 1.4 mm at implant placement in the reference group ( P = .065 ) . Two patients had minor perforations of the soft tissue exp and er . In the experimental group , the mean lateral bone augmentation after soft tissue expansion was 4.5 ± 1.3 mm , and after healing , it decreased to 3.9 ± 1.4 mm ( P = .063 ) . The mean vertical augmentation was 4.1 ± 1.7 mm and had decreased at implant placement to 3.0 ± 1.4 mm ( P = .041 ) . In the reference group , the mean lateral augmentation was 3.8 ± 0.8 mm , and after healing , it reduced to 2.7 ± 0.8 mm ( P = .024 ) . The mean vertical augmentation was 2.9 ± 0.9 mm , and after healing of the bone graft at implant placement , it was reduced to 1.6 ± 0.8 mm ( P = .01 ) . When smokers were excluded , there was significantly less resorption of the bone grafts in both lateral ( P = .049 ) and vertical ( P = .012 ) dimensions in the experimental group compared with the reference group . CONCLUSION Hydrogel expansion of the periosteum is an applicable method to achieve a surplus of soft tissue to cover bone grafts . More refinements to the technique may be required to minimize complications , especially in smoking patients PURPOSE This r and omized controlled trial compared fresh-frozen versus autologous bone blocks for maxillary horizontal ridge augmentation in patients with Cawood and Howell class IV atrophies . MATERIAL S AND METHODS Twenty-four patients were allocated to the autologous and fresh-frozen groups in a 1:1 ratio . Patients underwent computed tomography scans 1 week and 6 months after surgery for graft volume and density analysis . Doxycycline was administered at day 120 and day 150 to label new bone formation . Biopsy for histologic and histomorphometric analyses was performed at reentry for implant insertion , 6 months after grafting . RESULTS Fresh-frozen grafts had lower density than autologous bone . Autologous and fresh-frozen grafts lost , respectively , 25 % and 52 % of their initial volume ( p = .0041 ) . Histology revealed the presence of newly formed bone within both graft types , but clear signs of inflammation were present in fresh-frozen blocks . CONCLUSIONS According to these 6-month results , autologous bone blocks are preferable to fresh-frozen bone grafts BACKGROUND The aim of this study was to assess the influence of ridge morphology on the amount of horizontal bone augmentation achieved with the s and wich bone augmentation ( SBA ) technique in the reconstruction of buccal dehiscence defects on dental implants . METHODS Cone beam computed tomography ( CBCT ) was used to assess bone width changes in 26 patients who participated in a r and omized controlled trial conducted in 2008 to 2011 . The amount of horizontal bone gain was evaluated at four different levels ( 3 , 6 , 9 , and 12 mm apical to the alveolar crest ) and three different time points ( T1 : baseline , T2 : at time of graft placement , and T3 : 6 months later ) . Different morphological characteristics of the alveolar ridge were also evaluated to determine their influence on horizontal bone augmentation . A total of 78 CBCT scans were assessed . RESULTS Comparison of the changes in ridge morphology at all measurement locations showed an overall ridge width gain of 2.30 ± 2.20 mm after 6 months . The use of membranes and the angulation of the concavity played a role in influencing the outcomes of the SBA technique . Critical crest angulation ( CA ) is 150 ° for bone gain at 9 mm apical to the crest . When CA is smaller than 150 ° , the horizontal bone gain was 4.3 ± 2.2 mm ; if CA is greater than 150 ° , the gain was significantly lower at 1.3 ± 1.7 mm ( p = .001 ) . CONCLUSIONS SBA is a reliable and predictable technique to gain horizontal ridge width with simultaneous implant placement . Crest ridge angulation can be used as a tool to predict bone gain at 9 mm apical to the bone crest BACKGROUND There is limited evidence on the crestal bone level changes around implants placed in bone augmented by guided bone regeneration ( GBR ) during submerged healing . The purpose of this study was to prospect ively compare radiographic crestal bone changes around implants placed in augmented bone with changes around implants placed in pristine bone . MATERIAL S AND METHODS Patients receiving dental implants in the augmented or pristine m and ibular posterior edentulous ridge were included in the study . The digital st and ardized radiographs from the implant placement procedure were compared to the radiographs from the second-stage procedure to evaluate the peri-implant marginal bone level changes . The soft tissue thickness ( ST ) , width of keratinized mucosa ( wKM ) , and early cover screw exposure ( eIE ) were measured at the time of the second-stage procedure . RESULTS A total of 29 implants in 26 patients , 11 in augmented bone ( test group ) and 18 in pristine bone ( control group ) , were analyzed . The mean peri-implant bone loss ( ΔBL ) was 0.74 ± 0.74 mm ( mean ± SD ) in the test group and 0.25 ± 0.55 mm ( mean ± SD ) in the control group . The differences between the test and control groups in the mesial , distal , and mean peri-implant crestal bone level changes were statistically significant ( P = 0.009 , P = 0.004 , and P = 0.001 , respectively ) . The confounding factors ( ST , wKM , and eIE ) were adjusted . CONCLUSIONS More peri-implant crestal bone loss during the submerged healing period was observed in augmented bone than in pristine bone . Augmented bone may not exhibit the same characteristics as pristine bone during the implant submerged healing period OBJECTIVES The aim of the present r and omized-controlled double-blinded clinical multicenter study was to assess the use of either a new cross-linked ( VN ) or a native collagen membrane ( BG ) for the treatment of dehiscence-type defects at titanium implants . MATERIAL AND METHODS A total of n=54 patients were recruited in four German university clinics . According to a parallel-groups design , dehiscence-type defects at titanium implants were filled with a natural bone mineral and r and omly assigned to either VN or BG . Submerged sites were allowed to heal for 4 months . Primary ( e.g. , changes in defect length - DeltaDL , quality of newly formed tissue [ 0 - 4 ] - TQ ) and secondary parameters ( e.g. , membrane exposure , tissue conditions at dehisced sites ) were consecutively recorded . RESULTS Four patients were excluded due to an early wound infection ( VN:3 ; BG:1 ) , and one patient was lost during follow-up ( VN ) . The mean DeltaDL was 3.0 + /- 2.5 mm in the VN , and 1.94 + /- 2.13 mm in the BG group . The assessment of TQ revealed comparable mean values in both groups ( VN : 3.05 + /- 1.66 , BG : 3.46 + /- 1.48 ) . A significant correlation between membrane exposure and inflammation of the adjacent soft tissue was observed in the VN group . In both groups , the mean DL and TQ values were not significantly different at either non-exposed or exposed implant sites . CONCLUSION The results of the present study have indicated that VN supported bone regeneration on a level non-inferior to BG . However , in case of a premature membrane exposure , cross-linking might impair soft-tissue healing or may even cause wound infections The aim of this histologic , double-blind , parallel , r and omized controlled trial was to compare anorganic bone mineral-collagen membranes ( BB ) and betatricalcium phosphate-pericardium collagen membranes ( CJ ) in a one-stage procedure for horizontal bone augmentation . A biopsy was performed in the regenerated area at abutment connection 6 months after surgery . Five patients were assigned and treated with the BB combination and five patients were treated with the CJ combination . At abutment connection , 6 months after grafting , no significant differences were evident in the histomorphometric comparisons , even if the percentage of residual graft , using the marrow spaces and soft tissue as a reference , tended to be greater in the CJ group ( P = .0759 ) AIM This in vivo split-mouth r and omized controlled trial compared a synthetic bone substitute with a bovine bone mineral to cover bone dehiscences after implant insertion . MATERIAL S AND METHODS Fourteen patients received four to six implants to support an overdenture . Two comparable dehiscences within the same patient were first covered with a layer of autogenous bone , followed by a layer of either Bio-Oss ® ( group 1 ; Geistlich Pharma AG , Wolhusen , Switzerl and ) or Straumann BoneCeramic ® ( group 2 ; Institut Straumann AG , Basel , Switzerl and ) and sealed by a resorbable membrane . The change in vertical dimension of the defect was measured at implant placement and at abutment connection ( 6.5 months ) . Clinical and radiological parameters were evaluated up to 1 year of loading . RESULTS The vertical size of the defect at surgery was 6.4 ± 1.6 mm for group 1 and 6.4 ± 2.2 mm for group 2 sites , measured from the implant shoulder . After 6.5 months , the depth of the defect was reduced to 1.5 ± 1.2 mm and 1.9 ± 1.2 mm for group 1 and group 2 sites , respectively ( p > 0.05 ) . No implants failed during follow-up . Mean marginal bone loss over the SLActive surface was 0.94 mm ( group 1 ) , 0.81 mm ( group 2 ) , and 0.93 mm ( group 3 , no dehiscence ) after 1 year of loading . CONCLUSION Both bone substitutes behaved equally effectively The aim of this study was to longitudinally follow up osseointegrated titanium implants in partially dentate patients by clinical , radiographic and microbiological parameters in order to evaluate possible changes in the peri-implant health over time . Fifteen individuals treated with titanium implants , ad modum Brånemark , and followed for ten years were included in the study . Before implant placement ten years previously , the individuals had been treated for advanced periodontal disease and thereafter been included in a maintenance care program . The survival rate of the implants after ten years was 94.7 % . The bone loss was 1.7 mm when using the abutment-fixture junction as a reference point . Of the individuals , 50 % were positive for plaque at the implants . Bleeding on sulcus probing was present at 61 % of the implant surfaces . Ten years previously , the individuals had been carriers of putative periodontal pathogens , such as Porphyromonas gingivalis , Prevotella intermedia , Actinobacillus actinomycetemcomitans , Capnocytophaga spp . and Campylobacter rectus , and were also carriers of these species at the current examination . The results of the present study suggest that the presence of these putative periodontal pathogens at implants may not be associated with an impaired implant treatment . These species are most likely part of the normal resident microbiota of most individuals and may therefore be found at r and om at both stable and progressing peri-implant sites BACKGROUND Guided bone regeneration ( GBR ) is a viable treatment for osseous defects surrounding dental implants . Controversy exists regarding the choice of barrier membrane used and the method of membrane fixation to achieve GBR . METHODS This study compared the efficacy of a porcine-derived bioabsorbable collagen membrane and an exp and ed polytetrafluoroethylene ( ePTFE ) membrane ( non-resorbable ) for GBR using a bovine bone xenograft/autograft bone composite in defects surrounding dental implants . The study also examined the effect of primary barrier fixation on GBR . Defect size was recorded at Stage 1 and 2 surgeries ( performed 6 months apart ) . Forty-eight subjects ( 41 % males , 59 % females ) requiring GBR were treated with either collagen ( 23 ) or ePTFE ( 25 ) barriers , respectively . Implants were titanium self-tapping screw-type . In 34 GBR sites , barrier fixation was achieved with polylactic acid resorbable pins . The remaining barriers were secured with the implant cover screw and /or embedded beneath the flaps . RESULTS At 6 months , a decrease in defect width ( collagen barrier 1.95 + /- 0.60 mm , ePTFE barrier 2.65 + /- 0.56 mm ) , length ( collagen barrier 2.65 + /- 0.61 mm , ePTFE barrier 2.26 + /- 0.66 mm ) , and circumference ( degrees ) ( collagen barrier 57.7 + /- 18.7 , ePTFE barrier 80.2 + /- 19.9 ) was observed for both membranes . A significant number ( chi2 , P = 0.041 ) of postoperative complications occurred when barrier fixation was lacking at initial surgery . Furthermore , a significant difference ( P < 0.05 ) in the success of GBR with respect to defect size was observed when barrier fixation was taken into account . CONCLUSIONS In conclusion , both collagen and ePTFE barriers proved suitable for achieving GBR of osseous defects surrounding dental implants . The results of this study stress the importance of barrier fixation at the time of initial surgery OBJECTIVE The aim of the study was to radiologically and histologically evaluate the graft healing and volumetric changes after lateral augmentation with two different compositions of deproteinized bovine bone ( DPBB ) and autogenous bone ( AB ) . MATERIAL AND METHODS Thirteen patients with a mean age of 59.6 ± 12.1 years ( six men and seven women ) were included in this r and omized and controlled trial , design ed as a split-mouth study . Ten edentulous and four partially edentulous jaws with an alveolar ridge width of ≤4 mm were laterally augmented with a graft composition of 60 : 40 ( DPBB/AB ) on one side and 90 : 10 ( DPBB/AB ) on the contralateral side . Cone beam computed tomography ( CB/CT ) was obtained immediately postoperatively and after a healing period of 7.5 months . Width changes were measured on CB/CT scans . After a mean healing period of 8.1 months ( range , 7.9 - 8.3 ) , biopsies were retrieved perpendicular to the crest from each graft by means of a trephine bur . Histomorphometry was performed , and the following variables were recorded : Ingrowth of new bone ( percentage of total graft width ) , percentage of DPBB , bone and soft tissue , and percentage of DPBB particles in contact with bone . RESULTS The mean gained width of the alveolar crest after 7.5 months was significantly more for the 60 : 40 mixture compared with the 90 : 10 mixture , 3.5 ( ±1.3 ) mm and 2.9 ( ±1.3 ) mm , respectively . There was a significant difference in graft width reduction between 60 : 40 and 90 : 10 after 7.5 months , 37 (±19.9)% and 46.9 (±23.5)% , respectively . New bone ingrowth had occurred in 82.1 (±23.3)% and 82.3 (±26.6)% of the graft , respectively . There were no statistical differences between fractions of different tissues between the 90 : 10 and 60 : 40 compositions . However , there were significantly more soft tissue and less new bone formation closer to the periosteum compared with the graft portion closer to the residual bone in both 60 : 40 and 90 : 10 compositions . CONCLUSIONS There was significantly less graft width reduction with a mixture of 60 : 40 ( DPBB/AB ) compared with a mixture of 90 : 10 composition , but the results from the histomorphometry showed no statistical differences comparing the groups AIM The aim of the present study was to evaluate if the use of deprotenized bovine bone mineral ( DBBM ) and collagen barrier membranes ( CM ) in combination with m and ibular bone block grafts could reduce bone block graft resorption during healing . METHODS A prospect i ve r and omized controlled study has been design ed . Twenty-two ridges presenting horizontal alveolar deficiency ( crest width < 4 mm ) and at least two adjacent missing teeth were included in the study . In the control group , one or multiple m and ibular blocks were used to gain horizontal augmentation of the ridge . In the test group , DBBM granules were added at the periphery and over the graft . The reconstructions were covered by two layers of CM . Implants were placed 4 months after grafting . Direct measurements of crest width were performed before and immediately after bone augmentation , and immediately before implant placement . RESULTS Statistical analysis showed no significant differences in crest width between test and control groups at baseline and immediately after grafting . Mean augmentation at first surgery in the test group was 4.18 vs. 4.57 mm in the control group . Final gain obtained at the time of implant placement was 3.93 mm in the test and 3.67 mm in the control groups . The difference in mean graft resorption between test and control sites was statistically significant ( 0.25 mm in the test group vs. 0.89 mm in the control group , P=0.03 ) . Complications seem to occur more often in the test group ( complications recorded in three cases in the test group vs. one complication recorded in the control group ) . In all cases , implants could be placed in the planned sites and a total of 55 implants were placed ( 28 in the test group and 27 in the control group ) . All implants could be considered successfully integrated at the 24-month follow-up visit . CONCLUSION The results from this study showed that the addition of bovine bone mineral and a CM around and over a m and ibular bone block graft could minimize graft resorption during healing . On the other h and , the use of bone substitutes and barrier membranes in combination with block grafts increased the frequency of complications and the difficulty of their management |
11,285 | 10,796,365 | REVIEW ER 'S CONCLUSIONS ESD services provided for a selected group of stroke patients can reduce the length of hospital stay . | BACKGROUND Stroke patients conventionally receive a substantial part of their rehabilitation in hospital .
Services have now been developed which offer patients in hospital an early discharge with community-based rehabilitation ( early supported discharge , ESD ) .
OBJECTIVES The objective of this review is to establish the costs and effects of ESD services compared with conventional services . | BACKGROUND AND PURPOSE The goal of the present study was to examine the re source and economic implication s of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke . METHODS A cost minimization analysis in conjunction with a r and omized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide , South Australia , between 1997 and 1998 . Eighty-six hospitalized patients with acute stroke who required rehabilitation were r and omized to receive both early hospital discharge and home-based rehabilitation , or conventional in-hospital rehabilitation and community care . Direct and indirect costs related to stroke rehabilitation were calculated , including hospital bed days , home-based intervention program , community services , and personal expenses during the 6 months after r and omization . RESULTS The mean cost per patient was lower for patients r and omized to the early hospital discharge and home-based rehabilitation ( $ 8040 ) compared with those who received conventional care ( $ 10 054 ) . This cost saving was not statistically significant ( P=0.14 ) . However , sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50 % less than those used in the main analysis . Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient 's level of disability after adjustment for age , comorbidity , and the presence or absence of a caregiver . CONCLUSIONS The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke . Limitation of the provision of such services to patients with mild disability is likely to be most cost effective Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways Purpose : To evaluate the feasibility and effectiveness of early supported discharge ( ESD ) following acute stroke . Method : An ESD scheme was compared to conventional rehabilitation in a r and omized controlled trial . All patients admitted with acute stroke were considered for inclusion . Eighty-eight ( 20.2 % ) were found to be eligible and 82 were r and omized either to early supported discharge ( n=42 ) or conventional rehabilitation ( n=40 ) . The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale . The General Health Question naire , the Montgomery Aasberg Depression Rating Scale , mortality , placement and patient and carer satisfaction served as secondary outcome measures . Results : Median length of stay was reduced from 31 days in the conventional hospital rehabilitation group to 22 days in the early supported discharge group ( p=0.09 ) . No differences were found regarding primary outcome . The General Health Question naire score showed a significant difference in favour of the early supported discharge group at three months ( 19.5/24 , p = 0.02 ) , but not at six . At six months , the proportion of patients being dead or in institution showed a trend of being higher in the conventional rehabilitation group ( OR 3.8 , 95 % CI 0.8 - 23 ) . Conclusions : Early supported discharge after stroke is feasible and it is possible that it has benefits compared with conventional rehabilitation BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference in re source use during such a 3-month period was seen . A 52 % reduction in hospitalization was observed : from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group . Patient satisfaction was in favor of the latter group . CONCLUSIONS Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity BACKGROUND AND PURPOSE Organized acute stroke treatment reduces mortality , functional deficits , and the need of institutionalization after stroke . It is largely unknown whether the effects of treatment are due to early or subacute efforts . The aim of this r and omized , controlled study was to test the hypothesis that rehabilitation of stroke patients in the subacute phase in a hospital rehabilitation unit is beneficial in reducing death and dependency and increasing health-related quality of life . METHODS 251 patients initially treated in the hospital were r and omized to subacute rehabilitation in a hospital rehabilitation unit ( n = 127 ) or to the health services in the municipality ( n = 124 ) and were followed up for 7 months . RESULTS The combined outcome of patients being dead or dependent ( Barthel Index score of < 75 ) was 23 % in the hospital group and 38 % in the municipality group ( P=.01 ) . Seven-month survival rates were 90.6 % and 83.9 % ( P=.11 ) , respectively . Dependency in activities of daily living was 12.6 % in the hospital group and 25.0 % in the municipality group ( P=.07 ) . Patients with a BI score of < 50 before rehabilitation had significantly better outcome in the hospital rehabilitation unit , with fewer patients becoming dependent ( P=.005 ) and patients having higher Sc and inavian Stroke Scale ( P=.026 ) and BI scores ( P=.005 ) . No significant differences in health-related quality of life were found . Many patients treated in the municipalities ( 30 % ) did not receive any organized rehabilitation in this study . CONCLUSIONS Subacute rehabilitation of stroke patients in a hospital-based rehabilitation unit improves outcome . Patients with moderate or severe stroke appear to benefit most We previously conducted a r and omized controlled trial in which early supported discharge from the Department of Neurology at Huddinge Hospital in southwest Stockholm with continuity of rehabilitation at home ( n = 41 ) was compared to routine rehabilitation services ( n = 40 ) for moderately disabled selected stroke patients . No statistical significant differences were found in patient outcome at 3 or 6 months , but a moderately positive effect in the home rehabilitation group was suggested . In the present study we evaluated re source utilization of health and social care , impact on family caregivers during 6 months after acute stroke and patient satisfaction . A 50 % reduction in total hospitalization ( initial and recurrent ) was observed , from 30 days in the routine rehabilitation group to 15 days in the home rehabilitation group ( p < 0.001 ) . After discharge , the mean number of home visits in the home rehabilitation group was 12 . In total , the routine rehabilitation group had a higher frequency of therapy contacts and daycare in outpatient care . Seventy-eight percent received help from a family caregiver in activities of daily living , yet only 15 % had formal home help service . No major differences were found in use of home help service or impact on family caregivers in the form of time devoted to helping the patient or subjective well-being of spouses as per Sickness Impact Profile . Patient satisfaction was in favour of the home rehabilitation group , but a significant difference was only found in active participation in rehabilitation programme planning . In conclusion , early supported discharge with continuity of rehabilitation at home , using goal -directed functional activities based on the patient 's personal interests , should be the rehabilitation service of choice for moderately disabled stroke patients fulfilling certain criteria , provided that further evaluation during the first year after stroke reveals no great changes in outcome or re source use . More research into the effectiveness and cost implication s of early supported discharge with continuity of rehabilitation at home is needed in other parts of Sweden and in other countries before it can be asserted that the conclusions drawn from this study are applicable elsewhere Hospital-at-Home schemes have been cl aim ed to hasten the discharge of elderly orthopaedic patients , and are becoming increasingly popular with health service managers . In an attempt to measure the benefits of such a scheme when applied to elderly medical patients , we prospect ively r and omized 60 consecutive referrals of patients approaching discharge either to the Hospital-at-Home ( HAH ) rehabilitation team , or to conventional discharge ( CD ) preparation and domiciliary support . Patients allocated to HAH were discharged on average 5 days earlier than CD , while 64 % of each group remained at home during 6 months follow-up . Improvements in independence were modest , and similar in the two groups , though a trend favoured HAH Background and Purpose Several trials have shown that stroke unit care improves outcome for stroke patients . The aim of the present trial was to evaluate the effects of an extended stroke unit service ( ESUS ) , with early supported discharge , cooperation with the primary healthcare system , and more emphasis on rehabilitation at home as essential elements . Methods In a r and omized , controlled trial , 160 patients with acute stroke were allocated to the ESUS and 160 to the ordinary stroke unit service ( OSUS ) . The primary outcome was the proportion of patients who were independent as assessed by the modified Rankin Scale ( RS ) ( RS ≤2=global independence ) and independent in activities of daily living ( ADL ) as assessed by Barthel Index ( BI ) ( BI ≥95=independent in ADL ) after 26 weeks . Secondary outcomes were RS and BI scores after 6 weeks ; the proportion of patients at home , in institutions , and deceased after 6 and 26 weeks ; and the length of stay in institutions . Results After 26 weeks , 65.0 % in the ESUS versus 51.9 % in the OSUS group showed global independence ( RS ≤2 ) ( P= 0.017 ) , while 60.0 % in the ESUS versus 49.4 % in the OSUS group were independent in ADL ( BI ≥95 ) ( P = 0.056 ) . The odds ratios for independence ( ESUS versus OSUS ) were as follows : RS , 1.72 ( 95 % CI , 1.10 to 2.70 ) ; BI , 1.54 ( 95 % CI , 0.99 to 2.39 ) . At 6 weeks , 54.4 % of the ESUS group and 45.6 % of the OSUS group were independent according to RS ( P = 0.118 ) , and 56.3 % versus 48.8 % were independent according to BI ( P = 0.179 ) . The proportion of patients at home after 6 weeks was 74.4 % for ESUS and 55.6 % for OSUS ( P = 0.0004 ) , and the proportion in institutions was 23.1 % versus 40.0 % , respectively ( P = 0.001 ) . After 26 weeks , 78.8 % in the ESUS group versus 73.1 % in the OSUS were at home ( P = 0.239 ) , while 13.1 % versus 17.5 % were in institutions ( P = 0.277 ) . The mortality in the 2 groups did not differ . Average lengths of stay in an institution were 18.6 days in the ESUS and 31.1 days in the OSUS group ( P = 0.0324 ) . Conclusions An ESUS with early supported discharge seems to improve functional outcome and to reduce the length of stay in institutions compared with traditional stroke unit care Background and Purpose : This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke , at a minimum of 6 months after the intervention , in terms of patient outcome , re source use and health care cost . Methods : Eighty-three patients , moderately impaired 5–7 days after acute stroke , were included in a r and omized controlled trial , 42 being allocated to the intervention and 41 to routine rehabilitation . One-year follow-up of patient outcome included mortality , motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , and self-reported falls . Re source use over 12 months included inpatient hospital care , outpatient health care , use of health-related services , informal care , and cost of health care . Results : On univariate analysis there was no difference in patient outcome . Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living . A significant difference in inpatient hospital care , initial and recurrent , was observed , with a mean of 18 ( intervention ) versus 33 days ( control ) ( p = 0.002 ) . Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists ( p = 0.02 ) , private physical therapists ( p = 0.03 ) and day-hospital attendance ( p = < 0.001 ) , while the intervention group registered more visits to nurses in primary care ( p = 0.03 ) and home rehabilitation ( p = < 0.001 ) . Other differences in outcomes or re source utilization were nonsignificant . Conclusion : In Sweden , early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service , and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation Objective : To establish the feasibility and method of evaluation of an early supported hospital discharge policy for patients with acute stroke . Design : A r and omized controlled trial comparing an early supported discharge service to conventional care . Setting : Three acute hospitals in Newcastle upon Tyne . Subjects : Ninety-two eligible patients with acute stroke admitted between 1 February 1995 and 31 January 1996 . Main outcome measures : Placement , length of stay , readmission rates , mortality , functional ability ( Nottingham Extended Activities of Daily Living ( ADL ) Scale ) , h and icap ( Oxford H and icap Scale ) , global health status ( Dartmouth Coop Function Charts ) and carer stress ( General Health Question naire 30 item ) . Results : The median length of stay for patients r and omized to early supported discharge was 13 days compared to 22 days in the conventional care group ( p = 0.02 ) . The median Barthel ADL Index at seven days post stroke of patients r and omized to early supported discharge was 15 , and 13 for those r and omized to conventional care ( NS ) . At three months post stroke the median Nottingham EADL score of patients r and omized to early supported discharge was 10 compared to 7 for those who received conventional care ( NS ) . There were no statistically significant differences in the global health status of patients or carer stress . Conclusion : An early supported discharge service following acute stroke with individualized rehabilitation in the community is feasible and can be evaluated by a r and omized controlled trial but a larger multicentre trial is needed before such a service is widely adopted BACKGROUND The effects of residence in an acute geriatrics-based ward ( AGW ) with emphasis on early rehabilitation and discharge planning for older patients with acute medical illnesses were assessed . Outcome and use of re sources were compared with those of patients treated in general medical wards ( MWs ) . A per- protocol rather than intention-to-treat analysis was performed . METHODS A r and omized trial with 3-months follow-up . A total of 190 patients aged 70 years and older were r and omized to an acute geriatrics-based ward , and 223 patients were r and omized to general medical wards . RESULTS The two groups were comparable at inclusion . However , after care in the AGW , 71 % of patients could be discharged directly home compared with 64 % of those treated in MWs ( relative risk 1.17 ; 95 % CI , 0.93 - 1.49 ) . The length of stay was shorter in the AGW ( mean 5.9 vs 7.3 days ; P = .002 ) . The proportion of patients in geriatric or other hospital wards or in nursing homes did not differ , but the proportion of AGW patients in sheltered living tended to be lower ( P = .085 ) . At the follow-up , case fatality , ADL function , psychological well-being , need for daily personal assistance , drug consumption , need for readmission to hospital , and total health care costs after discharge did not differ between the two groups . Poor global outcome was observed in 37 % of AGW and 34 % of MW patients . CONCLUSIONS A geriatric approach with greater emphasis on early rehabilitation and discharge planning in the AGW shortened the length of hospital stay and may have reduced the need for long-term institutional living . This occurred despite patients in an acute geriatric ward not having better medical or functional outcome than older acute patients treated in general medical wards BACKGROUND AND PURPOSE Because stroke management is aim ed at facilitating community reintegration , it would be logical that the sooner the patient can be discharged home , the sooner reintegration can commence . The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function , community reintegration , and health-related quality of life during the first 3 months after stroke . METHODS A r and omized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home . When medically ready for discharge , persons with stroke were r and omized to either the home intervention group ( n=58 ) or the usual care group ( n=56 ) . The home group received a 4-week , tailor-made home program of rehabilitation and nursing services ; persons r and omized to the usual care group received services provided through a variety of mechanisms , depending on institutional , care provider , and personal preference . The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 ( SF-36 ) . Associated outcomes measures included the Timed Up & Go ( TUG ) , Barthel Index ( BI ) , the Older Americans Re source Scale for instrumental activities of daily living ( OARS-IADL ) , Reintegration to Normal Living ( RNL ) , and the SF-36 Mental Health component . RESULTS The total length of stay for the home group was , on average , 10 days , 6 days shorter than that for the usual care group . There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke ; however , there was a significantly beneficial impact of the home intervention on IADL and reintegration ( RNL ) . By 3 months after stroke , the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group . The total number of services received by the home group was actually lower than that received by the usual care group . CONCLUSIONS Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration , and these in turn were translated into a better physical health Abstract Objective : To assess the clinical effectiveness of an early discharge policy for patients with stroke by using a community based rehabilitation team . Design : R and omised controlled trial to compare conventional care with an early discharge policy . Setting : Two teaching hospitals in inner London . Subjects : 331 medically stable patients with stroke ( mean age 71 ) who lived alone and were able to transfer independently or who lived with a resident carer and were able to transfer with help . Interventions : 167 patients received specialist community rehabilitation for up to 3 months after r and omisation . 164 patients continued with conventional hospital and community care . Main outcome measures : Barthel score at 12 months . Secondary outcomes measured impairment with motoricity index , minimental state examination , and Frenchay aphasia screening test ; disability with the Rivermead activity of daily living scales , hospital anxiety and depression scale , and 5 m walk ; h and icap with the Nottingham health profile ; carer stress with caregiver strain index and patient and carer satisfaction . The main process measure was length of stay after r and omisation . Results : One year after r and omisation no significant differences in clinical outcomes were found apart from increased satisfaction with hospital care in the community therapy group . Length of stay after r and omisation in the community therapy group was significantly reduced ( 12 v 18 days ; P<0.0001 ) . Patients with impairments were more likely to receive treatment in the community therapy group . Conclusions : Early discharge with specialist community rehabilitation after stroke is feasible , as clinical ly effective as conventional care , and acceptable to patients . Considerable reductions in use of hospital beds are achievable . Key messages Early discharge from hospital after stroke with specialist rehabilitation at home is feasible without an increase in readmission rates or stress to carers This r and omised controlled trial shows this method to be as effective as conventional care when assessed with a range of measures of impairment , disability , h and icap , carer stress , and patient and carer satisfaction at 1 year Significant reductions in bed usage can be achieved by the provision of a community rehabilitation team with no significant increase in rehabilitation A r and omised controlled trial was conducted to assess whether a single intervention by a health visitor reduced the unplanned re-admission of elderly people discharged from geriatric wards . Two hundred and four consecutive discharges from geriatric wards were r and omly allocated to receive either a single visit from the health visitor at 72 h in addition to normal follow-up services or to a control group receiving the normal follow-up services . The primary outcome measure was the unplanned re-admissions over the following 6 months . There were 40 cases and 43 control patients with unplanned re-admissions in the first 6 months . The total lengths of the unplanned re-admissions were 1237 days for cases and 1427 for controls , an average of 12.1 days for cases and 14.0 for controls ( 95 % confidence interval -4.9 to 8.7 days , not significant ) . A visit by a health visitor to elderly patients after discharge from geriatric wards is unlikely to be of sufficient benefit to the patients for the service to be funded from a saving in unplanned re-admissions In a controlled trial of a home-care service available for the first 6 months after acute stroke , 440 patients received the new service and 417 patients were in the control group . The trial group used more hospital bed days , had a slightly higher admission rate , and did not show better emotional adjustment to stroke than the control group . There was no difference between the 2 groups in stress on relatives . Functional recovery was equal in the 2 groups . A quarter of patients managed at home in each group were severely disabled . Providing a new service does not necessarily alter clinical decisions in the short term , and care should be taken before exp and ing domiciliary services to reduce hospital use This prospect i ve r and omized controlled study was design ed to compare the treatment efficacy , safety and quality of life of ischemic stroke patients treated with conventional ( 10-day ) hospitalization or short ( 3-day ) hospitalization followed by home care treatment . One hundred and two patients with acute ischemic stroke who arrived within 48 h after symptom onset and met the inclusion criteria were studied . Patients were r and omly assigned to either of two groups of treatment . Patients in the ‘ hospitalization ’ group were hospitalized for 10 days , whereas those in the ‘ home care ’ group were admitted only for the first 3 days and were followed at home under the home care program . The baseline characteristics were similar in the two groups . There was no difference in the number of deaths or dependency defined by the Modified Rankin scale more than or equal to 3 between the two groups at 6 months . The relative risk was 0.85 with a 95 % confidence interval between 0.35 and 2.04 . There was also no difference in the number of patients who had good outcome ( NIHSS between 0 and 2 and Barthel index between 75 and 100 ) at 6 months . One patient in the home care group died due to massive intracerebral hemorrhage . Seventy-nine percent of patients in the home care group were satisfied with the home treatment program The Home Treatment Team ( HTT ) , a hospital discharge team for elderly patients , was created to provide practical help and promote independence of patients at home for up to 6 weeks after hospital discharge . Patients were those judged to be at particular risk of failing to resettle , and thus being readmitted to hospital or admitted to a residential or nursing home . An open r and omized controlled trial compared patients receiving the HTT ( n = 29 ) with controls ( n = 25 ) receiving appropriate conventional community services . Fewer HTT patients were readmitted ( four by 6 weeks and nine by 12 weeks ) than controls ( nine by 6 weeks and 14 by 12 weeks , p < 0.05 ) and more were at home at 6 weeks ( 24 , 83 % and 10 , 40 % , p < 0.05 ) , 12 weeks ( 21 , 72 % and 11 , 44 % , p < 0.05 ) and 12 months ( 17 , 58 % and 10 , 40 % , p < 0.05 ) . The HTT group spent fewer days in hospital than controls during 12 weeks ( median difference 34 days , 95 % confidence interval 0 - 75 , p < 0.05 ) and more days at home during 12 months ( 90 ; 247 - 0 , p = 0.02 ) . Neither group showed any significant change in mental state or functional abilities over 12 weeks . Potentially confounding factors were considered insufficient explanation for the difference in outcome between the groups . It is concluded that the HTT was of benefit but the mechanism of its effect was not identified BACKGROUND Organised specialist care for stroke improves outcome , but the merits of different methods of organisation are in doubt . This study compares the efficacy of stroke unit with stroke team or domiciliary care . METHODS A single-blind , r and omised , controlled trial was undertaken in 457 acute-stroke patients ( average age 76 years , 48 % women ) r and omly assigned to stroke unit , general wards with stroke team support , or domiciliary stroke care , within 72 h of stroke onset . Outcome was assessed at 3 , 6 , and 12 months . The primary outcome measure was death or institutionalisation at 12 months . Analyses were by intention to treat . FINDINGS 152 patients were allocated to the stroke unit , 152 to stroke team , and 153 to domiciliary stroke care . 51 ( 34 % ) patients in the domiciliary group were admitted to hospital after r and omisation . Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team ( 21/152 [ 14 % ] vs 45/149 [ 30 % ] ; p<0.001 ) or domiciliary care ( 21/152 [ 14 % ] vs 34/144 [ 24 % ] ; p=0.03 ) , mainly as a result of reduction in mortality . The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team ( 129/152 [ 85 % ] vs 99/149 [ 66 % ] ; p<0.001 ) or domiciliary care ( 129/152 [ 85 % ] vs 102/144 [ 71 % ] ; p=0.002 ) . These differences were present at 3 and 6 months after stroke . INTERPRETATION Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality , institutionalisation , and dependence after stroke |
11,286 | 20,055,730 | No pre-treatment patient variables were found to predict drop-out .
Consistently across studies , higher levels of pre-treatment symptomatic severity predicted higher levels of end-state symptomatic severity , but not degree of improvement .
There was some evidence that comorbid depression and avoidant personality disorder before treatment negatively influenced post-treatment end-state functioning , but not consistently improvement .
Generally , the results are in line with the conclusion that more disturbed patients with SP both begin and end treatment at a higher symptomatic level but with a similar degree of improvement . | BACKGROUND Although cognitive behavioural therapy ( CBT ) has been shown to be an efficacious treatment for social phobia ( SP ) , many patients drop out or achieve little or no benefit from treatment .
This fact is generally considered an argument for the importance of studies of predictor variables .
AIMS This paper systematic ally review s pre-treatment patient variables as predictors of drop-out from and outcome of CBT for SP . | In the present study , the role of individual response patterns in the treatment of social phobic patients was investigated . Seventy-four patients were diagnosed as social phobics . On the basis of extreme scores on a behavioral test ( the Simulated Social Interaction Test ) and on a cognitive measure ( the Rational Behavior Inventory ) , the response patterns of 39 patients were analyzed , and the patients themselves were classified as either ' behavioral reactors ' or ' cognitive reactors ' . Half of the patients with each response pattern received a behavioral focused treatment , i.e. social skills training ( SST ) , while the other half received a cognitive oriented treatment , i.e. rational emotive therapy ( RET ) . Patients received group therapy in eight weekly sessions . Within-group differences showed a considerable improvement in all treatment groups . Between-group differences failed to lend support to the hypothesis that treatment that fits a response pattern ( i.e. SST for behavioral reactors and RET for cognitive reactors ) will result in a greater improvement than one that does not Psychological group treatments , such as behavioral or cognitive-behavioral therapy , are generally effective interventions for social phobia . However , a substantial number of individuals discontinue these treatments prematurely . Participant attrition can threaten the validity of treatment outcome studies if attrition during therapy does not occur r and omly . In order to examine this issue , we studied 133 individuals with a principal diagnosis of social phobia who initiated a 12-week behavioral or cognitive-behavioral group treatment for social phobia . Thirty-four participants discontinued therapy prematurely . These dropouts were compared to treatment completers in demographic characteristics , Axis I and II psychopathology , and their attitude toward treatment . The results only showed a small difference between treatment completers and dropouts in their attitude toward treatment : dropouts rated the treatment rationale as less logical than completers at the beginning of treatment . No other differences between dropouts and completers were observed . Therefore , dropouts are unlikely to present a serious threat to the external validity of treatment outcome studies for social phobia Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Patients with depression are often excluded from studies on the treatment of social anxiety disorder ( SAD ) , leaving gaps in our knowledge about the impact of depressive affect on treatment for SAD . Patients participated in a r and omized , placebo‐controlled study of treatment for SAD . As in previous studies , patients were excluded from the study if they met criteria for major depressive disorder in the past 6 months . This exclusion notwithst and ing , patients who enrolled in the study exhibited a range of depressive symptoms , permitting an examination of the impact of depressive symptoms on treatment outcome for SAD . Assessment measures included the Clinical Global Impression Scale , Hamilton Rating Scale for Depression , Brief Social Phobia Scale , and Beck Depression Inventory . Higher levels of depressive symptoms were related to more severe social anxiety overall , and to less change in social anxiety symptoms over the course of the study . Patients who were deemed nonresponders to treatment had higher levels of depressive symptoms at pretreatment than those who responded . In addition , patients who dropped out of the study had higher levels of depressive symptoms at pretreatment than those who completed the study . These results suggest that modifications should be made to existing treatments to improve outcomes and decrease attrition in the substantial proportion of patients with SAD who also evidence depressive symptoms . Such modifications are likely to be more important when treating patients with SAD and comorbid major depressive disorder . Depression and Anxiety 22:161–167 , 2005 . © 2005 Wiley‐Liss , This study was a replication of a study on the prediction of treatment outcome in social phobic patients [ Chambless , D. L. , Tran , G. Q. Glass , C.R. ( 1997 ) . Predictors of response to cognitive-behavioral group therapy for social phobia . Journal of Anxiety Disorders , 11 221 - 240 ] . Results at the posttest and the 18-months follow-up were analyzed for DSM-III-R social phobic patients , with either a generalized social phobia ( n = 50 ) or a nongeneralized fear , i.e. fear of blushing , trembling or sweating in social situations ( n = 26 ) . Predictors were pretreatment depression , personality disorder traits , clinician rated severity of impairment and frequency of negative self-statements during social interactions . The criterium variable was ( the residual gain score of ) self-reported avoidance of social situations . In line with Chambless et al. , pretreatment depression showed some predictive value , but smaller and only at the posttest . Change in the frequency of negative self-statements paralleled , but did not predict , change in social phobia symptoms . In contrast with Chambless et al. , clinician rated severity was ( slightly ) predictive for treatment outcome , whereas avoidant personality traits had reverse correlations with outcome in both subgroups . The results are discussed and directions for further research are given Social phobia patients with fear of blushing , trembling , sweating and /or freezing as main complaint ( N = 65 ) were r and omly assigned to either task concentration training ( TCT ) or applied relaxation ( AR ) both followed by cognitive therapy ( CT ) . Measurements took place before and after wait-list , after TCT or AR ( within-test ) , after CT ( post-test ) , at 3-months and at 1-year follow-up . Effects were assessed on fear of showing bodily symptoms ( the central outcome variable ) , social phobia , other psychopathology , social skills , self-consciousness , self-focused attention , and dysfunctional beliefs . No changes occurred during wait-list . Both treatments were highly effective . TCT was superior to AR in reducing fear of bodily symptoms and dysfunctional beliefs at within-test . This difference disappeared after CT , at post-test and at 3-months follow-up . However , at 1-year follow-up the combination TCT-CT was superior to AR-CT in reducing fear of bodily symptoms , and effect sizes for TCT-CT reached 3 . Furthermore , at all assessment moments TCT or the combination TCT-CT was superior to AR-CT in reducing self-consciousness and self-focused attention . The superior long-term effect of TCT on fear of showing bodily symptoms is explained by lasting changes in attentional focus Ninety individuals with social phobia ( social anxiety disorder ) participated in a r and omized controlled trial and completed cognitive-behavioral group therapy , exposure group therapy without explicit cognitive interventions , or a wait-list control condition . Both treatments were superior to the wait-list group in reducing social anxiety but did not differ from one another at posttest . Changes in estimated social cost mediated treatment changes in both treatment conditions from pre- to posttest . However , only participants who received cognitive-behavioral therapy showed continued improvement from posttest to 6-month follow-up , which was associated with a reduction of estimated social cost from pretest to posttest . These results suggest that cognitive intervention leads to better maintenance of treatment gains , which is mediated through changes in estimated social cost |
11,287 | 23,127,305 | We found that active mobilization may improve muscle strength , functional independence , and the ability to wean from ventilation and may decrease the length of stay in the intensive care unit ( ICU ) and hospital .
Active mobilization appears to have a positive effect on physical function and hospital outcomes in mechanical ventilation patients . | OBJECTIVE To investigate the effectiveness and safety of active mobilization on improving physical function and hospital outcomes in patients undergoing mechanical ventilation for more than 24 hours . | The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease ( COPD ) is of growing interest , but often requires biopsies , usually with the Bergström technique . The current study was design ed to test the validity of a minimally invasive technique : the microbiopsy . In 17 patients with COPD and four normal subjects , two specimens of the vastus lateralis were taken percutaneously under local anaesthesia , one with a 16-gauge needle ( microbiopsy ) and the other with the Bergström needle . The enzymatic activity of citrate synthase ( CS ) and phosphofructokinase ( PFK ) , and the myosin heavy chain ( MyoHC ) composition were measured for both techniques . The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy . The microbiopsy sample weight reached 55±17 mg . The two techniques showed excellent agreement for CS activity and MyoHC composition . The PFK activity did not differ statistically between the techniques , but the agreement was moderate . The agreement between both biopsy techniques was stable over time . The median ( range ) fibre number within the microbiopsy specimens was 144 ( 38–286 ) . In conclusion , the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects , compared with the Bergström technique The aim of this study was to investigate the effects of mobilisation on respiratory and haemodynamic variables in the intubated , ventilated abdominal surgical patient . Mobilisation was defined as the progression of activity from supine , to sitting over the edge of the bed , st and ing , walking on the spot for one minute , sitting out of bed initially , and sitting out of bed for 20 minutes . Seventeen patients with age ( mean + /- SD ) 71.4 + /- 7.1 years satisfied inclusion criteria . Respiratory and haemodynamic parameters were measured in each of the above positions and compared with supine . In the 15 subjects who completed the protocol , st and ing result ed in significant increases in minute ventilation ( VE ) from 15.1 + /- 3.1 l/min in supine to 21.3 + /- 3.6 l/min in st and ing ( p < 0.001 ) . The increase in VE in st and ing was achieved by significant increases in tidal volume ( VT ) from 712.7 + /- 172.8 ml to 883.4 + /- 196.3 ml ( p = 0.008 ) and in respiratory rate ( fR ) from 21.4 + /- 5.0 breaths/min to 24.9 + /- 4.5 breaths/min ( p = 0.03 ) . No further increases were observed in these parameters beyond st and ing when activity was progressed to walking on the spot for one minute . When supine values were compared with walking on the spot for one minute , inspiratory flow rates ( VT/TI ) increased significantly from 683 + /- 131.8 ml/sec to 985.1 + /- 162.3 ml/sec ( p = 0.001 ) with significant increases in rib cage displacement ( p = 0.001 ) and no significant increase in abdominal displacement ( p = 0.23 ) . Arterial blood gases displayed no improvements following mobilisation . Changes in VT , fR , and VE were largely due to positional changes when moving from supine to st and ing Objective : To determine whether early activity is feasible and safe in respiratory failure patients . Design : Prospect i ve cohort study . Setting : From June 1 , 2003 , through December 31 , 2003 , we assessed safety and feasibility of early activity in all consecutive respiratory failure patients who required mechanical ventilation for > 4 days admitted to our respiratory intensive care unit ( RICU ) . A majority of patients were treated in another intensive care unit ( ICU ) before RICU admission . We excluded patients who required mechanical ventilation for ≤4 days . Patients : Eight‐bed RICU at LDS Hospital . Interventions : We assessed patients for early activity as part of routine respiratory ICU care . We prospect ively recorded activity events and adverse events . We defined three activity events as sit on bed , sit in chair , and ambulate . We defined six activity‐related adverse events as fall to knees , tube removal , systolic blood pressure > 200 mm Hg , systolic blood pressure < 90 mm Hg , oxygen desaturation < 80 % , and extubation . Measurements and Main Results : During the study period , we conducted a total of 1,449 activity events in 103 patients . The activity events included 233 ( 16 % ) sit on bed , 454 ( 31 % ) sit in chair , and 762 ( 53 % ) ambulate . In patients with an endotracheal tube in place , there were a total of 593 activity events , of which 249 ( 42 % ) were ambulation . There were < 1 % activity‐related adverse events , including fall to the knees without injury , feeding tube removal , systolic blood pressure > 200 mm Hg , systolic blood pressure < 90 mm Hg , and desaturation < 80 % . No patient was extubated during activity . Conclusions : We conclude that early activity is feasible and safe in respiratory failure patients . A majority of survivors ( 69 % ) were able to ambulate > 100 feet at RICU discharge . Early activity is a c and i date therapy to prevent or treat the neuromuscular complications of critical illness Objectives : To investigate whether a daily exercise session , using a bedside cycle ergometer , is a safe and effective intervention in preventing or attenuating the decrease in functional exercise capacity , functional status , and quadriceps force that is associated with prolonged intensive care unit stay . A prolonged stay in the intensive care unit is associated with muscle dysfunction , which may contribute to an impaired functional status up to 1 yr after hospital discharge . No evidence is available concerning the effectiveness of an early exercise training intervention to prevent these detrimental complications . Design : R and omized controlled trial . Setting : Medical and surgical intensive care unit at University Hospital Gasthuisberg . Patients : Ninety critically ill patients were included as soon as their cardiorespiratory condition allowed bedside cycling exercise ( starting from day 5 ) , given they still had an expected prolonged intensive care unit stay of at least 7 more days . Interventions : Both groups received respiratory physiotherapy and a daily st and ardized passive or active motion session of upper and lower limbs . In addition , the treatment group performed a passive or active exercise training session for 20 mins/day , using a bedside ergometer . Measurements and Main Results : All outcome data are reflective for survivors . Quadriceps force and functional status were assessed at intensive care unit discharge and hospital discharge . Six-minute walking distance was measured at hospital discharge . No adverse events were identified during and immediately after the exercise training . At intensive care unit discharge , quadriceps force and functional status were not different between groups . At hospital discharge , 6-min walking distance , isometric quadriceps force , and the subjective feeling of functional well-being ( as measured with “ Physical Functioning ” item of the Short Form 36 Health Survey question naire ) were significantly higher in the treatment group ( p < .05 ) . Conclusions : Early exercise training in critically ill intensive care unit survivors enhanced recovery of functional exercise capacity , self-perceived functional status , and muscle force at hospital discharge STUDY OBJECTIVES To evaluate the effects of early exercise training in patients recovering from acute respiratory failure needing mechanical ventilation ( MV ) . DESIGN Prospect i ve , r and omized , and controlled study . SETTING Three respiratory intermediate ICUs ( RIICUs ) . PATIENTS Of 228 patients admitted to an RIICU , 66 patients weaned from MV from > 48 to < 96 h were considered eligible and enrolled in the study . INTERVENTION Sixty-six patients were r and omized to either supported arm exercise training plus general physiotherapy ( gPT ) [ group 1 , 32 patients ] or to gPT alone ( group 2 , 34 patients ) . MEASUREMENTS AND RESULTS Twenty-five patients in each group completed the protocol . Group 1 showed a greater improvement in exercise capacity , as assessed by an arm incremental test ( IT ) [ p = 0.003 ] and an endurance test ( ET ) [ p = 0.021 ] , compared to group 2 . Posttraining maximal inspiratory pressure ( MIP ) significantly improved in both groups ( p < 0.001 and p = 0.003 in groups 1 and 2 respectively ; not significant ) . IT isoworkload dyspnea improved significantly in both groups ( p = 0.005 and p = 0.009 in groups 1 and 2 , respectively ; not significant between groups ) , whereas IT isoworkload peripheral muscle fatigue ( p < 0.001 ) , ET isotime dyspnea ( p < 0.01 ) , and ET isotime muscular fatigue ( p < 0.005 ) improved significantly in group 1 but not in group 2 . IT improvers ( chi2 = 0.004 ) and ET improvers ( chi2 = 0.047 ) were more frequently observed in group 1 than in group 2 . Baseline MIP could discriminate for IT ( p = 0.013 ; odds ratio [ OR ] , 1.116 ) and ET improvers ( p = 0.022 ; OR , 1.067 ) . CONCLUSION Early upper-limb exercise training is feasible in RIICU patients recently weaned from MV and can enhance the effects of gPT . Baseline inspiratory muscle function is related to exercise capacity improvement BACKGROUND : Chair-sitting may allow for more readily activated scalene , sternocleidomastoid , and parasternal intercostal muscles , and may raise and enlarge the upper thoracic cage , thereby allowing the thoracic cage to be more easily compressed . OBJECTIVE : To evaluate the effect of chair-sitting during exercise training on respiratory muscle function in mechanically ventilated patients . METHODS : We r and omized 16 patients to a control group and 18 patients to a chair-sitting group . The patients in the chair-sitting group were transferred by 2 intensive care unit nurses from bed to armchair and rested for at least 30 min , based on the individual patient 's tolerance . We measured heart rate , blood pressure , SpO2 , and respiratory rate . In the treatment group , before transferring the patient from bed to armchair , and 30 min after the completion of chair-sitting we measured respiratory muscle function variables , including the ratio of respiratory rate ( f ) to tidal volume ( VT ) , SpO2 , maximum inspiratory pressure ( PImax ) and maximum expiratory pressure ( PEmax ) . In the control patients we took those same measurements while the patient was in semirecumbent position , before and after treatments , for at least 6 days or until the patient was discharged from the intensive care unit or died . RESULTS : The 2 groups did not significantly differ in age , sex , or clinical outcomes . Respiratory rate , VT , f/VT , SpO2 , PImax , and PEmax were not significantly better in the chair-sitting group . The study period significantly improved respiratory rate , VT , PImax , and PEmax ( all P < .001 ) , but not f/VT . CONCLUSIONS : Six days of chair-sitting exercise training did not significantly improve respiratory muscle function in mechanically ventilated patients OBJECTIVE Patients in intensive care exhibit a high degree of loss of muscle mass . Appropriate instruments are needed to document muscle wasting in these patients . The aim of this pilot study was to describe muscle wasting in patients in the intensive care unit . DESIGN Two-fold study setting : prospect i ve longitudinal and cross-sectional single-blind . PATIENTS A total of 118 patients in the intensive care unit ( length of stay 1 - 98 days ; male : female ratio 88:30 ; age 55 + /- 17 years ) were included in a two-fold study setting . METHODS Muscle layer thickness of the M. quadriceps femoris was documented using ultrasound measurement at well-defined points . Seventeen pilot- patients were measured twice ; at baseline and after 28 days . In another group of 101 patients , muscle layer thickness was determined once after a r and om length of stay . The results of both groups were compared and correlated . RESULTS In both groups , M. quadriceps femoris thickness showed a significant negative correlation with length of stay in the intensive care unit ( p < 0.01 ) . Furthermore , muscle wasting in intensive care patients could be described using a logarithmic function . CONCLUSION Loss of muscle mass shows a negative correlation with length of stay , and seems to be higher during the first 2 - 3 weeks of immobilization/intensive care unit stay . Ultrasound is a valid and practical measurement tool for documenting muscle mass ( e.g. muscle layer thickness ) as part of the daily routine at an intensive care unit BACKGROUND : The functional status and outcomes in patients with prolonged mechanical ventilation ( PMV ) are often limited by poor endurance and pulmonary mechanics , which result from the primary diseases or prolonged time bedridden . We evaluate the impact of exercise training on pulmonary mechanics , physical functional status , and hospitalization outcomes in PMV patients . METHODS : Twenty-seven subjects with PMV in our respiratory care center ( RCC ) were divided r and omly into an exercise training group ( n = 12 ) and a control group ( n = 15 ) . The exercise program comprised 10 sessions of exercise training . The measurement of pulmonary mechanics and physical functional status ( Functional Independence Measurement and Barthel index ) were performed pre- study and post- study . The hospitalization outcomes included : days of mechanical ventilation , hospitalization days , and weaning and mortality rates during RCC stay . RESULTS : The training group had significant improvement in tidal volume ( 143.6 mL vs 192.5 mL , P = .02 ) and rapid shallow breathing index after training ( 162.2 vs 110.6 , P = .009 ) . No significant change was found in the control group except respiratory rate . Both groups had significant improvement in functional status during the study . However , the training group had greater changes in FIM score than the control group ( 44.6 vs 34.2 , P = .024 ) . The training group also had shorter RCC stay and higher weaning and survival rates than the control group , although no statistical difference was found . CONCLUSIONS : Subjects with PMV in our RCC demonstrated significant improvement in pulmonary mechanics and functional status after exercise training . The application of exercise training may be helpful for PMV patients to improve hospitalization outcomes Background and Purpose . Patients requiring prolonged mechanical ventilation ( PMV ) are frequently deconditioned because of respiratory failure precipitated by the underlying disease , the adverse effects of medications , and a period of prolonged immobilization . The effects of 6 weeks of physical training on the strength of respiratory and limb muscles , on ventilator-free time , and on functional status in patients requiring PMV were examined . Subjects . Thirty-nine patients with PMV were initially enrolled in the study and were assigned to either a treatment group ( n=20 ) or a control group ( n=19 ) . Three subjects in the treatment group and 4 subjects in the control group died during the 6-week intervention period and thus their data were excluded from the final analysis . Methods . Subjects in the treatment group received physical training 5 days a week for 6 weeks . Strength of respiratory and limb muscles , ventilator-free time , and functional status , which was measured by the Barthel Index of Activities of Daily Living ( BI ) and Functional Independence Measure ( FIM ) , were examined at baseline and at the third and sixth weeks of the study period . Results . Respiratory and limb muscle strength improved significantly at the third and sixth weeks in the treatment group compared with baseline measurements . Total BI and FIM scores increased significantly in the treatment group and remained unchanged in the control group . Effect sizes of the BI and FIM scores were 2.02 and 1.93 , respectively , at the sixth week . Discussion and Conclusion . The results show that a 6-week physical training program may improve limb muscle strength and ventilator-free time and thus improve functional outcomes in patients requiring PMV OBJECTIVE To examine differences in perceived quality of life ( QOL ) at 1 year postinjury between people with tetraplegia who required mechanical ventilation assistance at discharge from rehabilitation and those who did not . DESIGN Prospect i ve cross-sectional examination of people with spinal cord injury ( SCI ) drawn from the SCI Model Systems National Data base . SETTING Community . PARTICIPANTS People with tetraplegia ( N=1635 ) who sustained traumatic SCI between January 1 , 1994 , and September 30 , 2008 , who completed a 1-year follow-up interview , including 79 people who required at least some use of a ventilator at discharge from rehabilitation . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Satisfaction With Life Scale ( SWLS ) ; Craig H and icap Assessment and Reporting Technique (CHART)-Short Form Physical Independence , Mobility , Social Integration , and Occupation subscales ; Patient Health Question naire-9 ( PHQ-9 ) , Medical Outcomes Study 36-Item Short-Form Health Survey self-perceived health status . RESULTS Significant differences were found between the ventilator-user ( VU ) group and non-ventilator-user ( NVU ) group for cause of trauma , proportion with complete injury , neurologic impairment level , and number of rehospitalizations . The NVU group had significantly higher SWLS and CHART Social Integration scores than the VU group after controlling for selected covariates . The NVU group also had more positive perceived health status compared with a year previously and a lower incidence of depression assessed by using the PHQ-9 than the VU group . There were no significant differences between groups for perceived current health status . CONCLUSIONS People in this study who did not require mechanical ventilation at discharge from rehabilitation post-SCI reported generally better health and improved QOL compared with those who required ventilator assistance at 1 year postinjury . Nonetheless , the literature suggests that perceptions of QOL improve as people live in the community for longer periods Objective : Immobilization and subsequent weakness are consequences of critical illness . Despite the theoretical advantages of physical therapy to address this problem , it has not been shown that physical therapy initiated in the intensive care unit offers benefit . Design and Setting : Prospect i ve cohort study in a university medical intensive care unit that assessed whether a mobility protocol increased the proportion of intensive care unit patients receiving physical therapy vs. usual care . Patients : Medical intensive care unit patients with acute respiratory failure requiring mechanical ventilation on admission : Protocol , n = 165 ; Usual Care , n = 165 . Interventions : An intensive care unit Mobility Team ( critical care nurse , nursing assistant , physical therapist ) initiated the protocol within 48 hrs of mechanical ventilation . Measurements and Main Results : The primary outcome was the proportion of patients receiving physical therapy in patients surviving to hospital discharge . Baseline characteristics were similar between groups . Outcome data are reflective of survivors . More Protocol patients received at least one physical therapy session than did Usual Care ( 80 % vs. 47 % , p ≤ .001 ) . Protocol patients were out of bed earlier ( 5 vs. 11 days , p ≤ .001 ) , had therapy initiated more frequently in the intensive care unit ( 91 % vs. 13 % , p ≤ .001 ) , and had similar low complication rates compared with Usual Care . For Protocol patients , intensive care unit length of stay was 5.5 vs. 6.9 days for Usual Care ( p = .025 ) ; hospital length of stay for Protocol patients was 11.2 vs. 14.5 days for Usual Care ( p = .006 ) ( intensive care unit/hospital length of stay adjusted for body mass index , Acute Physiology and Chronic Health Evaluation II , vasopressor ) . There were no untoward events during an intensive care unit Mobility session and no cost difference ( survivors + nonsurvivors ) between the two arms , including Mobility Team costs . Conclusions : A Mobility Team using a mobility protocol initiated earlier physical therapy that was feasible , safe , did not increase costs , and was associated with decreased intensive care unit and hospital length of stay in survivors who received physical therapy during intensive care unit treatment compared with patients who received usual care OBJECTIVES To ( 1 ) reduce deep sedation and delirium to permit mobilization , ( 2 ) increase the frequency of rehabilitation consultations and treatments to improve patients ' functional mobility , and ( 3 ) evaluate effects on length of stay . DESIGN Seven-month prospect i ve before/after quality improvement project . SETTING Sixteen-bed medical intensive care unit ( MICU ) in academic hospital . PARTICIPANTS 57 patients mechanically ventilated 4 days or longer . INTERVENTION A multidisciplinary team focused on reducing heavy sedation and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines . MAIN OUTCOME MEASURES Sedation and delirium status , rehabilitation treatments , functional mobility . RESULTS Compared with before the quality improvement project , benzodiazepine use decreased markedly ( proportion of MICU days that patients received benzodiazepines [ 50 % vs 25 % , P=.002 ] ) , with lower median daily sedative doses ( 47 vs 15 mg midazolam equivalents [ P=.09 ] and 71 vs 24 mg morphine equivalents [ P=.01 ] ) . Patients had improved sedation and delirium status ( MICU days alert [ 30 % vs 67 % , P<.001 ] and not delirious [ 21 % vs 53 % , P=.003 ] ) . There were a greater median number of rehabilitation treatments per patient ( 1 vs 7 , P<.001 ) with a higher level of functional mobility ( treatments involving sitting or greater mobility , 56 % vs 78 % , P=.03 ) . Hospital administrative data demonstrated that across all MICU patients , there was a decrease in intensive care unit and hospital length of stay by 2.1 ( 95 % confidence interval : 0.4 - 3.8 ) and 3.1 ( 0.3 - 5.9 ) days , respectively , and a 20 % increase in MICU admissions compared with the same period in the prior year . CONCLUSIONS Using a quality improvement process , intensive care unit delirium , physical rehabilitation , and functional mobility were markedly improved and associated with decreased length of stay OBJECTIVE Pulmonary rehabilitation has been shown to be of benefit to clinical ly stable patients with chronic obstructive pulmonary disease ( COPD ) . This study examined the effect of pulmonary rehabilitation on some physiologic variables in COPD patients recovering from an episode of acute respiratory failure . DESIGN A prospect i ve , r and omized study . SETTING A respiratory intensive care unit ( RICU ) . PATIENTS Eighty COPD patients recovering from an episode of acute respiratory failure were r and omized in a 3:1 fashion to receive stepwise pulmonary rehabilitation ( group A , n=60 patients ) or st and ard medical therapy ( group B , n=20 patients ) . MAIN OUTCOME MEASURES Improvements in exercise tolerance , sense of breathlessness , respiratory muscle function , and pulmonary function test values were measured , respectively , by exercise capacity ( 6-minute walking distance [ 6MWD ] ) , dyspnea score ( Visual Analog Scale [ VAS ] ) , maximal inspiratory pressure ( MIP ) , forced expiratory volume in 1 second ( FEV1 ) , and forced vital capacity ( FVC ) . INTERVENTIONS Group A received pulmonary rehabilitation that consisted of passive mobilization ( step I ) , early deambulation ( step II ) , respiratory and lower skeletal muscle training ( step III ) , and if the patients were able , complete lower extremity training on a treadmill ( step IV ) . Group B received st and ard medical therapy plus a basic deambulation program . RESULTS Sixty-one of 80 patients were mechanically ventilated at admission to the unit and most of them were bedridden . Twelve of the 60 group A patients and 4 of the 20 group B patients died during their RICU stay , and 9 patients required invasive mechanical ventilation at home after their discharge . The total length of RICU stay was 38+/-14 days for patients in group A versus 33.2+/-11 days for those in group B. Most patients from both groups regained the ability to walk , either unaided or aided . At discharge , 6 MWD results were significantly improved ( p < .001 ) in Group A only . MIP improved in Group A only ( p < .05 ) , while VAS scores improved in both groups , but the improvement was more marked in group A ( p < .001 ) than in group B ( p < .05 ) . CONCLUSIONS COPD patients who were admitted to a RICU in critical condition after an episode of acute respiratory failure and who , in most cases , required mechanical ventilation benefited from comprehensive early pulmonary rehabilitation , compared with patients who received st and ard medical therapy and progressive ambulation Objective Examine postdischarge mortality , quality of life , and charges for care for short-term ( > 24 and ≤96 hrs of ventilation ) and long-term ( > 96 hrs ) ventilator patients . Design Prospect i ve longitudinal descriptive study . Setting Posthospital discharge follow-up in homes , nursing homes , and rehabilitation centers . Patients Intensive care unit patients who required > 24 hrs of continuous in-hospital mechanical ventilation were enrolled from February 1997 through March 1999 . Patients living to hospital discharge were followed for 1 yr postdischarge . Interventions None . Measurements and Results A total of 538 patients were studied . In-hospital mortality was 47.4 % , with a 1-yr mortality rate of 64.7 % ; survival analysis showed that the different survival risks for short-term and long-term ventilator patients over time were not statistically significant . Long-term patients were more likely to be discharged to a nursing home ( 45.2 % ) . Short-term ventilator patients had better overall quality of life at all points postdischarge . Charges to produce a long-term survivor were significantly higher than for short-term patients ; on average $ 86,360 more charges were required to produce a long-term ventilator patient survivor for 1 yr postdischarge . Conclusions There were no significant demographic or clinical differences between short-term and long-term ventilator patients . Our results suggest that the likelihood of need for continued care in an extended-care facility for months and the risk of death during the first year postdischarge are sufficiently common features of this population and need to be included in discussion s of treatment options with patients and their families The aim of this study was to assess the effect of physiotherapy on ventilator dependency and lengths of intensive care unit ( ICU ) stay . Patients were divided into two groups . The control group , which received st and ard nursing care , was a retrospective chart review . The data of control patients who were not receiving physiotherapy were obtained from the hospital records . The intervention group was prospect ively taken into the chest physiotherapy program . This study was planned on mechanically ventilated patients who were admitted to a six-bed multidisciplinary internal medicine intensive care unit of the university hospital . A total of 510 patients who were hospitalised in the ICU were included in the study . Demographics , diagnostic profiles , co-existing chronic diseases , respiratory parameters on admission , patient 's overall severity by Acute Physiology and Chronic Health Evaluation II score , patient outcome , duration of stay in ICU , duration of ventilator support , and complications were assessed . The extubation time and length of ICU stay were compared between the two groups . Control patients had a longer period of ventilator dependency than the intervention patients and this difference was statistically significant ( P<0.05 ) . It was noted that the result ing length of stay in the ICU was significantly lower in the intervention group than in the control group ( P<0.05 ) . Although the patients had similar diagnoses and physical features , the length of stay in the ICU was significantly lower in the intervention group . The results show that physiotherapy has a great impact on ventilatory dependency and length of stay in the ICU BACKGROUND / PURPOSE Early physical training is necessary for severely deconditioned patients undergoing prolonged mechanical ventilation ( PMV ) , because survivors often experience prolonged recovery . Long-term outcomes after physical training have not been measured ; therefore , we investigated outcome during a 1-year period after physical training for the PMV patients . METHODS We conducted a prospect i ve r and omized control trial in a respiratory care center . Thirty-four patients were r and omly assigned to the rehabilitation group ( n = 18 ) and the control group ( n = 16 ) . The rehabilitation group participated in supervised physical therapy training for 6 weeks , and continued in an unsupervised maintenance program for 6 more weeks . The functional independence measurement ( FIM ) was used to assess functional status . Survival status during the year after enrollment , the number of survivors discharged , and the number free from ventilator support were collected . These outcome parameters were assessed at entry , immediately after the 6 weeks physical therapy training period , after 6 weeks unsupervised maintenance exercise program , and 6 months and 12 months after study entry . RESULTS The scores of total FIM , motor domain , cognitive domain , and some sub-items , except for the walking/wheelchair sub-item , increased significantly in the rehabilitation group at 6 months postenrollment , but remained unchanged for the control group . The eating , comprehension , expression , and social interaction subscales reached the 7-point complete independence level at 6 months in the rehabilitation group , but not in the control group . The 1-year survival rate for the rehabilitation group was 70 % , which was significantly higher than that for the control group ( 25 % ) , although the proportion of patients discharged and who were ventilator-free in the rehabilitation and control groups did not differ significantly . CONCLUSION Six weeks physical therapy training plus 6 weeks unsupervised maintenance exercise enhanced functional levels and increased survival for the PMV patients compared with those with no such intervention . Early physical therapy interventions are needed for the PMV patients in respiratory care centers BACKGROUND : Rehabilitation is a non-pharmacologic therapy that can restore health and reverse the patient 's disability , but the efficacy of rehabilitation in critically ill patients is not well documented . METHODS : In a prospect i ve cohort study , we assessed whether the degree of change in functional status after comprehensive rehabilitation influenced clinical outcomes in 77 tracheotomized patients ( mean ± SD age 75 ± 7 y ) admitted for difficult weaning to our regional weaning center . The care plan , including peripheral muscle training , was delivered daily . We recorded admission demographic , anthropometric , and functional characteristics . We measured the change in basic activities of daily living score ( ΔBADL ) , survival , and weaning success rate as clinical outcomes . We performed the Pearson correlation analysis and linear regression , with ΔBADL as the dependent variable , to test the predictive power of the baseline measurements . RESULTS : Sixty-seven patients ( 87 % ) survived , and 55 of them ( 74 % ) succeeded in weaning during their stay in the weaning center . The mean ± SD ΔBADL improvement was 2.5 ± 2.0 points ( median 2 points ) . Baseline performance of the latissimus dorsi predicted ΔBADL ( β = 0.388 , 95 % CI 0.111–1,664 , P = .03 ) . The probability of remaining ventilator-free ( P = .043 ) and survival ( P = .001 ) differed across the 4 ΔBADL categories ( 0 = no change , 1–2 = least improvement , and > 2 = improvement above median change ) . CONCLUSIONS : Mortality rate and weaning success differ according to ΔBADL following active rehabilitation/training in tracheotomized , ventilated , difficult-to-wean patients . The performance of the latissimus dorsi was the only significant predictor of change QUESTIONS Does a 12-week , predominantly home-based program of progressive resistance exercises reduce impairments , activity limitations , and participation restrictions in people with chronic obstructive pulmonary disease ? Are any gains maintained 12 weeks after the cessation of the program ? DESIGN R and omised controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 54 people with moderately severe chronic obstructive pulmonary disease not undergoing pulmonary rehabilitation . INTERVENTION The experimental group performed six progressive resistance exercises three times per week ( once a week hospital-based , twice a week home-based ) for 12 weeks . Exercise intensity was three sets of 8 to 12 repetition maximum progressed against elasticised b and s of increasing resistance . The control group received no intervention . OUTCOME MEASURES Primary outcomes were strength ( knee extensor , hip abductor , shoulder horizontal flexor , shoulder flexor ) measured using h and -held dynamometry , and walking capacity measured by the 6-minute Walk Test performed before and after intervention and again at 12 weeks after the cessation of intervention . RESULTS The experimental group increased their knee extensor strength by 4.9 kg ( 95 % CI 1.1 to 8.7 ) more than the control group by Week 12 . However , this gain was not maintained at Week 24 . No difference between the groups was found for any of the other primary outcomes . CONCLUSIONS A predominantly home-based progressive resistance exercise program led to modest improvements in knee extensor strength in people with chronic obstructive pulmonary disease . However , 44 % of the experimental group were unable to complete the exercise program , highlighting the need to underst and factors influencing adherence to exercise in this population CONTEXT Although electrophysiologic and histologic neuromuscular abnormalities are common in intensive care unit ( ICU ) patients , the clinical incidence of ICU-acquired neuromuscular disorders in patients recovering from severe illness remains unknown . OBJECTIVES To assess the clinical incidence , risk factors , and outcomes of ICU-acquired paresis ( ICUAP ) during recovery from critical illness in the ICU and to determine the electrophysiologic and histologic patterns in patients with ICUAP . DESIGN Prospect i ve cohort study conducted from March 1999 to June 2000 . SETTING Three medical and 2 surgical ICUs in 4 hospitals in France . PARTICIPANTS All consecutive ICU patients without preexisting neuromuscular disease who underwent mechanical ventilation for 7 or more days were screened daily for awakening . The first day a patient was considered awake was day 1 . Patients with severe muscle weakness on day 7 were considered to have ICUAP . MAIN OUTCOME MEASURES Incidence and duration of ICUAP , risk factors for ICUAP , and comparative duration of mechanical ventilation between ICUAP and control patients . RESULTS Among the 95 patients who achieved satisfactory awakening , the incidence of ICUAP was 25.3 % ( 95 % confidence interval [ CI ] , 16.9%-35.2 % ) . All ICUAP patients had a sensorimotor axonopathy , and all patients who underwent a muscle biopsy had specific muscle involvement not related to nerve involvement . The median duration of ICUAP after day 1 was 21 days . Mean ( SD ) duration of mechanical ventilation after day 1 was significantly longer in patients with ICUAP compared with those without ( 18.2 [ 36.3 ] vs 7.6 [ 19.2 ] days ; P = .03 ) . Independent predictors of ICUAP were female sex ( odds ratio [ OR ] , 4.66 ; 95 % CI , 1.19 - 18.30 ) , the number of days with dysfunction of 2 or more organs ( OR , 1.28 ; 95 % CI , 1.11 - 1.49 ) , duration of mechanical ventilation ( OR , 1.10 ; 95 % CI , 1.00 - 1.22 ) , and administration of corticosteroids ( OR , 14.90 ; 95 % CI , 3.20 - 69.80 ) before day 1 . CONCLUSIONS Identified using simple bedside clinical criteria , ICUAP was frequent during recovery from critical illness and was associated with a prolonged duration of mechanical ventilation . Our findings suggest an important role of corticosteroids in the development of ICUAP PURPOSE The aim of this study was to describe the frequency , physiologic effects , safety , and patient outcomes associated with traditional rehabilitation therapy in patients who require mechanical ventilation . MATERIAL S AND METHODS Prospect i ve observational report of consecutive patients ventilated 4 or more days and eligible for rehabilitation in a single medical intensive care unit ( ICU ) during a 13-week period was conducted . RESULTS Of the 32 patients who met the inclusion criteria , only 21 ( 66 % ) received physician orders for evaluation by rehabilitation services ( physical and /or occupational therapy ) . Fifty rehabilitation treatments were provided to 19 patients on a median of 12 % of medical ICU days per patient , with deep sedation and unavailability of rehabilitation staff representing major barriers to treatment . Physiologic changes during rehabilitation therapy were minimal . Joint contractures were frequent in the lower extremities and did not improve during hospitalization . In 53 % and 79 % of initial ICU assessment s , muscle weakness was present in upper and lower extremities , respectively , with a decreased prevalence of 19 % and 43 % at hospital discharge , respectively . New impairments in physical function were common at hospital discharge . CONCLUSIONS This pilot project illustrated important barriers to providing rehabilitation to mechanically ventilated patients in an ICU and impairments in strength , range of motion , and functional outcomes at hospital discharge Purpose . To evaluate the functional status of patients within the first week of discharge from an intensive care unit ( ICU ) , and to identify predictors and explanatory factors of functional status . Methods . A prospect i ve , observational , cohort study was conducted with consecutive ICU patients who had stayed in a mixed , closed-format , university-level ICU for longer than 48 h. Results . Between 3 and 7 days of discharge from the ICU , functional status ( as primary outcome ) , walking ability , muscle strength , and sensory and cognitive functioning were assessed in 69 survivors . The overall functional status was poor ( median Barthel Index 6 ) . In their ability to perform basic activities of daily living , 67 % percent were severely dependent , 15 % were moderately dependent , and 9 % were slightly dependent on other people . Independent walking was impossible for 73 % of participants , grip strength was reduced for 50 % , and 30 % had cognitive impairments . Duration of ventilation was associated with functional status after ICU discharge . Reduced grip strength and walking ability were identified as explanatory factors for poorer functional status shortly after discharge from the ICU . Conclusion . In the first week after discharge from the ICU , the majority of the patients had substantial functional disabilities in activities of daily living . These disabilities were more severe in patients who experienced ventilation for a longer period of time . There is a need for prospect i ve studies focusing on functional recovery to support informed decision-making concerning the care of critically ill patients after ICU discharge RATIONALE ICU-acquired paresis ( ICUAP ) is common in survivors of critical illness . There is significant associated morbidity , including prolonged time on the ventilator and longer hospital stay . However , it is unclear whether ICUAP is independently associated with mortality , as sicker patients are more prone and existing studies have not adjusted for this . OBJECTIVES To test the hypothesis that ICUAP is independently associated with increased mortality . Secondarily , to determine if h and grip dynamometry is a concise measure of global strength and is independently associated with mortality . METHODS A prospect i ve multicenter cohort study was conducted in intensive care units ( ICU ) of five academic medical centers . Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength . MEASUREMENTS AND MAIN RESULTS We measured global strength and h and grip dynamometry . The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days , ICU readmission , and recurrent respiratory failure . Subjects with ICUAP ( average MRC score of < 4 ) had longer hospital stays and required mechanical ventilation longer . H and grip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP . After adjustment for severity of illness , ICUAP was independently associated with hospital mortality ( odds ratio [ OR ] , 7.8 ; 95 % confidence interval [ CI ] , 2.4 - 25.3 ; P = 0.001 ) . Separately , h and grip strength was independently associated with hospital mortality ( OR , 4.5 ; 95 % CI , 1.5 - 13.6 ; P = 0.007 ) . CONCLUSIONS ICUAP is independently associated with increased hospital mortality . H and grip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP . Clinical trial registered with www . clinical trials.gov ( NCT00106665 ) |
11,288 | 28,535,331 | Although our review suggests that interventions aim ed at facilitating , supporting , and sustaining self-managment in people with COPD and delivered via smart technology significantly improved HRQoL and levels of activity up to six months compared with interventions given through face-to-face/digital and /or written support , no firm conclusions can be drawn .
This improvement may not be sustained over a long duration .
The only included study that measured outcomes up to 12 months highlighted the need to ensure sustained engagement with the technology over time .
Limited evidence suggests that using computer and mobile technology for self-management for people with COPD is not harmful and may be more beneficial for some people than for others , for example , those with an interest in using technology may derive greater benefit .
The evidence , provided by three studies at high risk of bias , is of poor quality and is insufficient for advising healthcare professionals , service providers , and members of the public with COPD about the health benefits of using smart technology as an effective means of supporting , encouraging , and sustaining self-management . | BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is characterised by airflow obstruction due to an abnormal inflammatory response of the lungs to noxious particles or gases , for example , cigarette smoke .
The pattern of care for people with moderate to very severe COPD often involves regular lengthy hospital admissions , which result in high healthcare costs and an undesirable effect on quality of life .
Research over the past decade has focused on innovative methods for developing enabling and assistive technologies that facilitate patient self-management .
OBJECTIVES To evaluate the effectiveness of interventions delivered by computer and by mobile technology versus face-to-face or hard copy/digital documentary-delivered interventions , or both , in facilitating , supporting , and sustaining self-management among people with COPD . | In international and national guidelines patient education is recommended as an integral part of an effective management for both , asthma and COPD , respectively . The evaluation of numerous structured education programs for adult asthmatics revealed an increase of quality of life of the educated patients , reduced morbidity with less asthmatic attacks , a decrease of emergency visits , sick leave days and hospitalizations due to asthma . On the basis of cost/benefit analysis cost effectiveness could be demonstrated for education programs for asthmatics . On the basis of education programs in COPD including self-management , in a r and omized controlled study an improvement of the patient 's ability to react to exacerbations could be shown , thus reducing the morbidity by the disease . Further controlled studies of the effects of patient education on morbidity , mortality and cost effectiveness are necessary to establish the role of structured education programs in the treatment of COPD with sufficient validity Introduction COPD is a leading cause of morbidity and mortality . Self-management interventions are considered important in order to limit the progression of the disease . Computer-tailored interventions could be an effective tool to facilitate self-management . Methods This r and omized controlled trial tested the effectiveness of a web-based , computer-tailored COPD self-management intervention on physical activity and smoking behavior . Participants were recruited from an online panel and through primary care practice s. Those at risk for or diagnosed with COPD , between 40 and 70 years of age , proficient in Dutch , with access to the Internet , and with basic computer skills ( n=1,325 ) , were r and omly assigned to either the intervention group ( n=662 ) or control group ( n=663 ) . The intervention group received the web-based self-management application , while the control group received no intervention . Participants were not blinded to group assignment . After 6 months , the effect of the intervention was assessed for the primary outcomes , smoking cessation and physical activity , by self-reported 7-day point prevalence abstinence and the International Physical Activity Question naire – Short Form . Results Of the 1,325 participants , 1,071 ( 80.8 % ) completed the 6-month follow-up question naire . No significant treatment effect was found on either outcome . The application however , was used by only 36 % of the participants in the experimental group . Conclusion A possible explanation for the nonsignificant effect on the primary outcomes , smoking cessation and physical activity , could be the low exposure to the application as engagement with the program has been shown to be crucial for the effectiveness of computer-tailored interventions . ( Netherl and s Trial Registry number : NTR3421 . Background Low levels of physical activity are common in patients with chronic obstructive pulmonary disease ( COPD ) , and a sedentary lifestyle is associated with poor outcomes including increased mortality , frequent hospitalizations , and poor health-related quality of life . Internet-mediated physical activity interventions may increase physical activity and improve health outcomes in persons with COPD . Methods / Design This manuscript describes the design and rationale of a r and omized controlled trial that tests the effectiveness of Taking Healthy Steps , an Internet-mediated walking program for Veterans with COPD . Taking Healthy Steps includes an uploading pedometer , a website , and an online community . Eligible and consented patients wear a pedometer to obtain one week of baseline data and then are r and omized on a 2:1 ratio to Taking Healthy Steps or to a wait list control . The intervention arm receives iterative step-count feedback ; individualized step-count goals , motivational and informational messages , and access to an online community . Wait list controls are notified that they are enrolled , but that their intervention will start in one year ; however , they keep the pedometer and have access to a static webpage . Discussion Participants include 239 Veterans ( mean age 66.7 years , 93.7 % male ) with 155 r and omized to Taking Healthy Steps and 84 to the wait list control arm ; rural-living ( 45.2 % ) ; ever-smokers ( 93.3 % ) ; and current smokers ( 25.1 % ) . Baseline mean St. George ’s Respiratory Question naire Total Score was 46.0 ; 30.5 % reported severe dyspnea ; and the average number of comorbid conditions was 4.9 . Mean baseline daily step counts was 3497 ( + /- 2220).Veterans with COPD can be recruited to participate in an online walking program . We successfully recruited a cohort of older Veterans with a significant level of disability including Veterans who live in rural areas using a remote national recruitment strategy .Trial registration Clinical Trials.gov Computer-tailored printed education can be a promising way of promoting physical activity . The present study tested whether computer-tailored feedback on physical activity is effective and whether there are differences between respondents with low and high motivation to change . Respondents ( n = 487 ) were r and omly assigned to a tailored intervention group or a no information control group . Physical activity and determinants were measured at baseline and after 3 months . At post-test , the motivated respondents in the control group were more likely not to meet the recommendation for physical activity than to meet it , and motivated respondents in the experimental group were more likely to engage in transport-related activities and showed more improvement over time for the total activity score than respondents in the control group ( beta = 0.24 , P = 0.02 ) . Both groups improved their behaviour over time . No group differences in physical activity were found for the unmotivated respondents . The results showed that the effects of the tailored feedback were restricted to respondents who had a positive motivation to change at baseline . Possible explanations could be that unmotivated respondents were unwilling to read and process the information because they felt ' no need to change ' . Alternatively , one tailored feedback letter may not have been sufficient for this unmotivated group Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) Background Distributing a multiple computer-tailored smoking cessation intervention through the Internet has several advantages for both provider and receiver . Most important , a large audience of smokers can be reached while a highly individualized and personal form of feedback can be maintained . However , such a smoking cessation program has yet to be developed and implemented in the Netherl and s. Objective To investigate the effects of a Web-based multiple computer-tailored smoking cessation program on smoking cessation outcomes in a sample of Dutch adult smokers . Methods Smokers were recruited from December 2009 to June 2010 by advertising our study in the mass media and on the Internet . Those interested and motivated to quit smoking within 6 months ( N = 1123 ) were r and omly assigned to either the experimental ( n = 552 ) or control group ( n = 571 ) . Respondents in the experimental group received the fully automated Web-based smoking cessation program , while respondents in the control group received no intervention . After 6 weeks and after 6 months , we assessed the effect of the intervention on self-reported 24-hour point prevalence abstinence , 7-day point prevalence abstinence , and prolonged abstinence using logistic regression analyses . Results Of the 1123 respondents , 449 ( 40.0 % ) completed the 6-week follow-up question naire and 291 ( 25.9 % ) completed the 6-month follow-up question naire . We used a negative scenario to replace missing values . That is , we considered respondents lost to follow-up to still be smoking . The computer-tailored program appeared to have significantly increased 24-hour point prevalence abstinence ( odds ratio [ OR ] 1.85 , 95 % confidence interval [ CI ] 1.30–2.65 ) , 7-day point prevalence abstinence ( OR 2.17 , 95 % CI 1.44–3.27 ) , and prolonged abstinence ( OR 1.99 , 95 % CI 1.28–3.09 ) rates reported after 6 weeks . After 6 months , however , no intervention effects could be identified . Results from complete-case analyses were similar . Conclusions The results presented suggest that the Web-based computer-tailored smoking cessation program had a significant effect on abstinence reported after a 6-week period . At the 6-month follow-up , however , no intervention effects could be identified . This might be explained by the replacement of missing values on the primary outcome measures due to attrition using a negative scenario . While results were similar when using a less conservative scenario ( ie , complete-case analyses ) , the results should still be interpreted with caution . Further research should aim at identifying strategies that will prevent high attrition in the first place and , subsequently , to identify the best strategies for dealing with missing data when studies have high attrition rates . Trial Registration Dutch Trial Register NTR1351 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1351 ( Archived by WebCite at http://www.webcitation.org/67egSTWrz The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease ( COPD ) telehealth program applied in both primary and secondary care . The program consisted of four modules : 1 ) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior , 2 ) web-based exercise program for home exercising , 3 ) self-management of COPD exacerbations via a triage diary on the web portal , including self-treatment of exacerbations , and 4 ) teleconsultation . Twenty-nine COPD patients were r and omly assigned to either the intervention group ( telehealth program for 9 months ) or the control group ( usual care ) . Page hits on the web portal showed the use of the program , and the Client Satisfaction Question naire showed satisfaction with received care . The telehealth program with decision support showed good satisfaction ( mean 26.4 , maximum score 32 ) . The program was accessed on 86 % of the treatment days , especially the diary . Patient adherence with the exercise scheme was low ( 21 % ) . Health care providers seem to play an important role in patients ’ adherence to telehealth in usual care . Future research should focus on full-scale implementation in daily care and investigating technological advances , like gaming , to increase adherence Inhaled medication is important in the treatment of chronic obstructive pulmonary disease ( COPD ) . In this paper a comparison of the long-term efficacy of three instruction-models is presented . A total of 152 COPD - patients were r and omized into one of four groups : Personal- , video- , group-instruction and a control group . Inhalation technique was assessed by means of checklists , on which essential inhalation manoeuvres were identified . Up to 9 months later , 148 patients returned for follow-up assessment . Prior to instruction 61 % of patients in the control group had a perfect score on essential actions , compared to 62 , 65 and 53 % for those receiving group- , personal- and video-instruction respectively . At follow-up these percentages were 49 , 97 , 75 and 76 % . For group-(35 % ) and video-instruction ( 24 % ) the increase from baseline was significant . Examining the different inhalers under investigation , it is striking , that only 24 % of all patients with a Metered Dose Inhaler ( MDI ) performed all essential checklist items correctly , versus 96 % for those using a Diskhaler . The fact that for the MDI this percentage improved to 90 % post-instruction , shows that time spent on instruction , is time well spent . We conclude that group instruction seems superior to personal counselling , and equally effective or even better than video instruction . Personal instruction should not be dismissed and a combination with video instruction might prove to be effective as well Background Regular physical activity ( PA ) is recommended for persons with chronic obstructive pulmonary disease ( COPD ) . Interventions that promote PA and sustain long-term adherence to PA are needed . Objective We examined the effects of an Internet-mediated , pedometer-based walking intervention , called Taking Healthy Steps , at 12 months . Methods Veterans with COPD ( N=239 ) were r and omized in a 2:1 ratio to the intervention or wait-list control . During the first 4 months , participants in the intervention group were instructed to wear the pedometer every day , upload daily step counts at least once a week , and were provided access to a website with four key components : individualized goal setting , iterative feedback , educational and motivational content , and an online community forum . The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content . Participants r and omized to the wait-list control group were instructed to wear the pedometer , but they did not receive step-count goals or instructions to increase PA . The primary outcome was health-related quality of life ( HRQL ) assessed by the St George ’s Respiratory Question naire Total Score ( SGRQ-TS ) ; the secondary outcome was daily step count . Linear mixed-effect models assessed the effect of intervention over time . One participant was excluded from the analysis because he was an outlier . Within the intervention group , we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data , number of log-ins to the website each month , use of the online community forum , and responses to a structured survey . Results Participants were 93.7 % male ( 223/238 ) with a mean age of 67 ( SD 9 ) years . At 12 months , there were no significant between-group differences in SGRQ-TS or daily step count . Between-group difference in daily step count was maximal and statistically significant at month 4 ( P<.001 ) , but approached zero in months 8 - 12 . Within the intervention group , mean 76.7 % ( SD 29.5 ) of 366 days had valid step-count data , which decreased over the months of study ( P<.001 ) . Mean number of log-ins to the website each month also significantly decreased over the months of study ( P<.001 ) . The online community forum was used at least once during the study by 83.8 % ( 129/154 ) of participants . Responses to questions assessing participants ’ goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months . Conclusions An Internet-mediated , pedometer-based PA intervention , although efficacious at 4 months , does not maintain improvements in HRQL and daily step counts at 12 months . Waning pedometer adherence and website engagement by the intervention group were observed . Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA . Clinical Trial Clinical trials.gov NCT01102777 ; https:// clinical trials.gov/ct2/show/NCT01102777 ( Archived by WebCite at http://www.webcitation.org/6iyNP9KUC Background Chronic Obstructive Pulmonary Disease ( COPD ) is a major cause of morbidity and mortality . Effective self-management support interventions are needed to improve the health and functional status of people with COPD or at risk for COPD . Computer-tailored technology could be an effective way to provide this support . Methods / Design This paper presents the protocol of a r and omised controlled trial testing the effectiveness of a web-based , computer-tailored self-management intervention to change health behaviours of people with or at risk for COPD . An intervention group will be compared to a usual care control group , in which the intervention group will receive a web-based , computer-tailored self-management intervention . Participants will be recruited from an online panel and through general practice s. Outcomes will be measured at baseline and at 6 months . The primary outcomes will be smoking behaviour , measuring the 7-day point prevalence abstinence and physical activity , measured in minutes . Secondary outcomes will include dyspnoea score , quality of life , stages of change , intention to change behaviour and alternative smoking behaviour measures , including current smoking behaviour , 24-hour point prevalence abstinence , prolonged abstinence , continued abstinence and number of quit attempts . Discussion To the best of our knowledge , this will be the first r and omised controlled trial to test the effectiveness of a web-based , computer-tailored self-management intervention for people with or at risk for COPD . The results will be important to explore the possible benefits of computer-tailored interventions for the self-management of people with or at risk for COPD and potentially other chronic health conditions . Dutch trial Background Breathing programs have been reported to have positive effects in alleviating symptoms and optimizing pulmonary function in patients with chronic obstructive pulmonary disease ( COPD ) . However , patients with stable disease may drop out of such programs if they are not modified to the individual ’s exercise tolerance level , or if they are not easy to perform in the home . Little is known about the effectiveness of web-based home breathing programs for dyspnea . The purpose of this study was to evaluate the effectiveness of an online breathing program which included an animated diagram and video-guided instruction on pulmonary function , exercise capacity , and health-related quality of life in patients with COPD . Methods Sixty patients with stable COPD were r and omized 1:1 to an experimental group ( n = 30 ) or a control group ( n = 30 ) . Subjects in the experimental group trained for four months using an online program which included an animated diagram and video-guided instruction while the control group received conventional patient education on discharge from hospital . Forced expiratory volume , forced expiratory volume in one second (FEV1)/forced vital capacity ( % ) , peak expiratory volume , six-minute walking distance test , and responses to the St George ’s Respiratory Question naire were assessed before and after the intervention . Results Patients in the two groups were well matched for demographic and clinical characteristics at baseline . All outcome measures showed significant improvement in the experimental group but not in the control group . Conclusion The online training program result ed in improved pulmonary function , exercise capacity , and health status . Therefore , it is strongly recommended that patients with stable COPD be trained with such programs Background People with chronic obstructive pulmonary disease ( COPD ) continue to experience dyspnea with activities of daily living ( ADL ) despite optimal medical management . Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs . Objective The purpose of this r and omized study was to test the efficacy of two 6-month dyspnea self-management programs , Internet-based ( eDSMP ) and face-to-face ( fDSMP ) , on dyspnea with ADL in people living with COPD . Methods We r and omly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP ( n = 26 ) or fDSMP ( n = 24 ) group . The content of the two programs was similar , focusing on education , skills training , and ongoing support for dyspnea self-management , including independent exercise . The only difference was the mode ( Internet/personal digital assistant [ PDA ] or face-to-face ) in which the education sessions , reinforcement contacts , and peer interactions took place . Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months . The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Question naire . Secondary outcomes of exercise behavior , exercise performance , COPD exacerbations , and mediators , such as self-efficacy and social support , were also measured . A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit . Results The study was stopped early due to multiple technical challenges with the eDSMP , but follow-up was completed on all enrolled participants . Data were available for 39 participants who completed the study ( female : 44 % ; age : 69.5 ± 8.5 years ; percent predicted forced expiratory volume in 1 s : 49.6 ± 17.0 % ) . The fDSMP and eDSMP showed similar clinical ly meaningful changes in dyspnea with ADL from baseline to 3 months ( fDSMP : + 3.3 points ; eDSMP : + 3.5 points ) and sustained these improvements at 6 months ( fDSMP : + 4.0 points ; eDSMP : + 2.5 points ; time effects P < .001 ; group by time P = .51 ) . Self-reported endurance exercise time ( P = .001 ) , physical functioning ( P = .04 ) , and self-efficacy for managing dyspnea ( P = .02 ) also showed positive improvements over time in both groups with no significant differences with respect to program modality . Participants who completed the study reported favorable satisfaction with the programs . Conclusions Although there were numerous technical challenges with the eDSMP , both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term . Our findings will need to be confirmed in a larger r and omized trial with more mature Web and personal digital assistant tools , use of a control group , and longer follow-up . Trial registration clinical trials.gov NCT00102401 , Introduction The potential for telehealth-based interventions to provide remote support , education and improve self-management for long-term conditions is increasingly recognised . This trial aims to determine whether an intervention delivered through an easy-to-use tablet computer can improve the quality of life of patients with chronic obstructive pulmonary disease ( COPD ) by providing personalised self-management information and education . Methods and analysis The EDGE ( sElf management anD support proGrammE ) for COPD is a multicentre , r and omised controlled trial design ed to assess the efficacy of an Internet-linked tablet computer-based intervention ( the EDGE platform ) in improving quality of life in patients with moderate to very severe COPD compared with usual care . Eligible patients are r and omly allocated to receive the tablet computer-based intervention or usual care in a 2:1 ratio using a web-based r and omisation system . Participants are recruited from respiratory outpatient clinics and pulmonary rehabilitation courses as well as from those recently discharged from hospital with a COPD -related admission and from primary care clinics . Participants allocated to the tablet computer-based intervention complete a daily symptom diary and record clinical symptoms using a Bluetooth-linked pulse oximeter . Participants allocated to receive usual care are provided with all the information given to those allocated to the intervention but without the use of the tablet computer or the facility to monitor their symptoms or physiological variables . The primary outcome of quality of life is measured using the St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) baseline , 6 and 12 months . Secondary outcome measures are recorded at these intervals in addition to 3 months . Ethics and dissemination The Research Ethics Committee for Berkshire — South Central has provided ethical approval for the conduct of the study in the recruiting regions . The results of the study will be disseminated through peer review publications and conference presentations . Trial registration Current controlled trials IS RCT N40367841 BACKGROUND Low levels of physical activity ( PA ) are associated with poor outcomes in people with COPD . Interventions to increase PA could improve outcomes . METHODS We tested the efficacy of a novel Internet-mediated , pedometer-based exercise intervention . Veterans with COPD ( N = 239 ) were r and omized in a 2:1 ratio to the ( 1 ) intervention group ( Omron HJ-720 ITC pedometer and Internet-mediated program ) or ( 2 ) wait-list control group ( pedometer ) . The primary outcome was health-related quality of life ( HRQL ) , assessed by the St. George 's Respiratory Question naire ( SGRQ ) , at 4 months . We examined the SGRQ total score ( SGRQ-TS ) and three domain scores : Symptoms , Activities , and Impact . The secondary outcome was daily step counts . Linear regression models assessed the effect of intervention on outcomes . RESULTS Participants had a mean age of 67 ± 9 years , and 94 % were men . There was no significant between-group difference in mean 4-month SGRQ-TS ( 2.3 units , P = .14 ) . Nevertheless , a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS , the minimum clinical ly important difference ( 53 % vs 39 % , respectively , P = .05 ) . For domain scores , the intervention group had a lower ( reflecting better HRQL ) mean than the control group by 4.6 units for Symptoms ( P = .046 ) and by 3.3 units for Impact ( P = .049 ) . There was no significant difference in Activities score between the two groups . Compared with the control subjects , intervention participants walked 779 more steps per day at 4 months ( P = .005 ) . CONCLUSIONS An Internet-mediated , pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01102777 ; URL : www . clinical trials.gov Patients hospitalised for exacerbations contribute significantly to the total chronic obstructive pulmonary disease ( COPD ) -related healthcare costs . This study aim ed to determine the re source use and costs of exacerbations by exacerbation-severity and to identify risk factors for hospitalisation . Exacerbations and the details of all associated healthcare utilisation were recorded as part of a prospect i ve cost-effectiveness analysis linked to two r and omised controlled trials comparing tiotropium with ipratropium in 519 patients with stable COPD at study entry in the Netherl and s and Belgium . Exacerbation-severity was rated by the physician . A Cox proportional hazards analysis was performed to identify independent risk factors of hospitalisation . Covariates that entered this analysis were smoking status , pack-years , body mass index , number of concomitant diseases , number of concomitant medications , use of inhaled steroids , physician visits prior to trial , FEV1 % predicted , quality of life , baseline dyspnea index ( BDI ) and treatment arm . The mean number of exacerbations per patient was 0.70 ( 95%-CI:0.60 , 0.81 ) . About 10 % of the exacerbations was severe , 47 % moderate and 43 % was mild . The mean costs of these exacerbations were Euro 4007 ( 95%-CI:2004 , 6011 ) , Euro 579 ( 390 , 768 ) and Euro 86 ( 49 , 124 ) , respectively . In addition to treatment arm , a body mass index below 18.5 ( RR:3.62 ) , each additional concomitant diagnosis ( RR:1.40 ) and a decrease of 1 point in the baseline dyspnea index ( RR:1.18 ) were significant risk factors of hospitalisation . Exacerbations that were associated with a hospitalisation accounted for 90 % of the total costs of exacerbations . Underweight , history of concomitant diseases and increased dyspnea ( BDI score ) are factors that are likely to identify patients who are at increased risk for generating high costs due to hospitalisation CONTEXT People with chronic obstructive pulmonary disease experience dyspnea with activities despite optimal medical management . OBJECTIVES The purpose of this study was to test the efficacy of two 12-month dyspnea self-management programs ( DSMPs ) , Internet-based ( eDSMP ) and face-to-face ( fDSMP ) , compared with a general health education ( GHE ) control on the primary outcome of dyspnea with activities . METHODS Participants with chronic obstructive pulmonary disease were r and omized to eDSMP ( n=43 ) , fDSMP ( n=41 ) , or GHE ( n=41 ) . The content of the DSMPs were similar and focused on education , skills training , and coaching on dyspnea self-management strategies , including exercise , and only differed in the delivery mode . Dyspnea with activities was measured with the Chronic Respiratory Question naire at three , six , and 12 months . Secondary outcomes included exercise behavior and performance , health-related quality of life , self-efficacy for dyspnea management , and perception of support for exercise . The study was registered at Clinical trials.gov ( NCT00461162 ) . RESULTS There were no differences in dyspnea with activities across groups over 12 months ( P=0.48 ) . With the exception of arm endurance ( P=0.04 ) , exercise behavior , performance , and health-related quality of life did not differ across groups ( P>0.05 ) . Self-efficacy for managing dyspnea improved for the DSMPs compared with GHE ( P=0.06 ) . DSMP participants perceived high levels of support for initiating and maintaining an exercise program . CONCLUSION The DSMPs did not significantly reduce dyspnea with activities compared with attention control . However , the high participant satisfaction with the DSMPs combined with positive changes in other outcomes , including self-efficacy for managing dyspnea and exercise behavior , highlight the need for additional testing of individually tailored technology-enabled interventions to optimize patient engagement and improve clinical ly relevant outcomes Objective : First , to investigate the effects of a telerehabilitation intervention on health status and activity level of patients with Chronic Obstructive Pulmonary Disease ( COPD ) , compared to usual care . Second , to investigate how patients comply with the intervention and whether compliance is related to treatment outcomes . Design : a r and omized controlled pilot trial Subjects : Thirty-four patients diagnosed with COPD . Intervention : The telerehabilitation application consists of an activity coach ( 3D-accelerometer with smartphone ) for ambulant activity registration and real-time feedback , complemented by a web portal with a symptom diary for self-treatment of exacerbations . The intervention group used the application for 4 weeks . The control group received usual care . Main measures : Activity level measured by a pedometer ( in steps/day ) , health status by the Clinical COPD Question naire at baseline and after intervention . Compliance was expressed as the time the activity coach was worn . Results : Fourteen intervention and 16 control patients completed the study . Activity level ( steps/day ) was not significantly affected by the intervention over time . There was a non-significant difference in improvement in health status between the intervention ( −0.34±0.55 ) and control group ( 0.02±0.57 , p=0.10 ) . Health status significantly improved within the intervention group ( p=0.05 ) . The activity coach was used more than prescribed ( 108 % ) and compliance was related to the increase in activity level for the first two feedback weeks ( r=0.62 , p=0.03 ) . Conclusions : This pilot study shows the potential of the telerehabilitation intervention : compliance with the activity coach was high , which directly related to an improvement in activity levels |
11,289 | 26,553,896 | High-intensity TCIs ( combining home visits with telephone followup , clinic visits , or both ) reduced readmission risk regardless of the duration of follow-up .
High-intensity interventions seem to be the best option .
Moderate-intensity interventions implemented for 6 months or longer may be another option | PURPOSE We aim ed to determine the impact of transitional care interventions ( TCIs ) on acute health service use by patients with congestive heart failure in primary care and to identify the most effective TCIs and their optimal duration . | BACKGROUND Heart failure treatment guidelines emphasize daily weight monitoring for patients with heart failure , but data to support this practice are lacking . Using a technology-based heart failure monitoring system , we determined whether daily reporting of weight and symptoms in patients with advanced heart failure would reduce rehospitalization and mortality rates despite aggressive guideline -driven heart failure care . METHODS This was a r and omized , controlled trial . Patients hospitalized with New York Heart Association class III or IV heart failure , with a left ventricular ejection fraction < or = 35 % were r and omized to receive heart failure program care or heart failure program care plus the AlereNet system ( Alere Medical , Reno , Nev ) and followed-up for 6 months . The primary end point was 6-month hospital readmission rate . Secondary end points included mortality , heart failure hospitalization readmission rate , emergency room visitation rate , and quality of life . RESULTS Two hundred eighty patients from 16 heart failure centers across the United States were r and omized : 138 received the AlereNet system and 142 received st and ard care . Mean age was 59 + /- 15 years and 68 % were male . The population had very advanced heart failure , New York Heart Association class III ( 75 % ) or IV ( 25 % ) , as evidence d by serum norepinepherine levels , 6-minute walk distance and outcomes . No differences in hospitalization rates were observed . There was a 56.2 % reduction in mortality ( P < .003 ) for patients r and omized to the AlereNet group . CONCLUSIONS This is the largest multicenter , r and omized trial of a technology-based daily weight and symptom-monitoring system for patients with advanced heart failure . Despite no difference in the primary end point of rehospitalization rates , mortality was significantly reduced for patients r and omized to the AlereNet system without an increase in utilization , despite specialized and aggressive heart failure care in both groups AIMS To test the effect of education and support by a nurse on self-care and re source utilization in patients with heart failure . METHODS A total of 179 patients ( mean age 73 , 58 % male , NYHA III-IV ) hospitalized with heart failure were evaluated prospect ively . Patients were r and omized to the study intervention or to ' care as usual ' . The supportive educative intervention consisted of intensive , systematic and planned education by a study nurse about the consequences of heart failure in daily life , using a st and ard nursing care plan developed by the research ers for older patients with heart failure . Education and support took place during the hospital stay and at a home visit within a week of discharge . Data were collected on self-care abilities , self-care behaviour , readmissions , visits to the emergency heart centre and use of other health care re sources . RESULTS Education and support from a nurse in a hospital setting and at home significantly increases self-care behaviour in patients with heart failure . Patients from both the intervention and the control group increased their self-care behaviour within 1 month of discharge , but the increase in the intervention group was significantly more after 1 month . Although self-care behaviour in both groups decreased during the following 8 months , the increase from baseline remained statistically significant in the intervention group , but not in the control group . No significant effects on re source utilization were found . CONCLUSIONS Intensive , systematic , tailored and planned education and support by a nurse results in an increase in patients ' self-care behaviour . No significant effects were found on use of health care re sources . Additional organisational changes , such as longer follow-up and the availability of a heart failure specialist would probably enhance the effects of education and support Abstract Objectives : To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure . Design : R and omised controlled trial . Setting : Acute medical admissions unit in a teaching hospital . Participants : 165 patients admitted with heart failure due to left ventricular systolic dysfunction . The intervention started before discharge and continued thereafter with home visits for up to 1 year . Main outcome measures : Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure . Results : 31 patients ( 37 % ) in the intervention group died or were readmitted with heart failure compared with 45 ( 53 % ) in the usual care group ( hazard ratio=0.61 , 95 % confidence interval 0.33 to 0.96).Compared with usual care , patients in the intervention group had fewer readmissions for any reason ( 86 v 114 , P=0.018 ) , fewer admissions for heart failure ( 19 v 45 , P<0.001 ) and spent fewer days in hospital for heart failure ( mean 3.43 v 7.46 days , P=0.0051 ) . Conclusions : Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure . What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896 OBJECTIVES We sought to identify whether home telemonitoring ( HTM ) improves outcomes compared with nurse telephone support ( NTS ) and usual care ( UC ) for patients with heart failure who are at high risk of hospitalization or death . BACKGROUND Heart failure is associated with a high rate of hospitalization and poor prognosis . Telemonitoring could help implement and maintain effective therapy and detect worsening heart failure and its cause promptly to prevent medical crises . METHODS Patients with a recent admission for heart failure and left ventricular ejection fraction ( LVEF ) < 40 % were assigned r and omly to HTM , NTS , or UC in a 2:2:1 ratio . HTM consisted of twice-daily patient self-measurement of weight , blood pressure , heart rate , and rhythm with automated devices linked to a cardiology center . The NTS consisted of specialist nurses who were available to patients by telephone . Primary care physicians delivered UC . The primary end point was days dead or hospitalized with NTS versus HTM at 240 days . RESULTS Of 426 patients r and omly assigned , 48 % were aged > 70 years , mean LVEF was 25 % ( SD , 8) and median plasma N-terminal pro-brain natriuretic peptide was 3,070 pg/ml ( interquartile range 1,285 to 6,749 pg/ml ) . During 240 days of follow-up , 19.5 % , 15.9 % , and 12.7 % of days were lost as the result of death or hospitalization for UC , NTS , and HTM , respectively ( no significant difference ) . The number of admissions and mortality were similar among patients r and omly assigned to NTS or HTM , but the mean duration of admissions was reduced by 6 days ( 95 % confidence interval 1 to 11 ) with HTM . Patients r and omly assigned to receive UC had higher one-year mortality ( 45 % ) than patients assigned to receive NTS ( 27 % ) or HTM ( 29 % ) ( p = 0.032 ) . CONCLUSIONS Further investigation and refinement of the application of HTM are warranted because it may be a valuable role for the management of selected patients with heart failure OBJECTIVES We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure ( CHF ) hospital readmissions and mortality over a six-month period . BACKGROUND Hospital admission for CHF is an important problem amenable to improved outpatient management . METHODS Two hundred patients hospitalized with CHF at increased risk of hospital readmission were r and omized to a multidisciplinary program or usual care . A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient 's primary physician before r and omization . The intervention team consisted of a cardiologist , a CHF nurse , a telephone nurse coordinator and the patient 's primary physician . Contact with the patient was on a prespecified schedule . The CHF nurse followed an algorithm to adjust medications . Patients in the nonintervention group were followed as usual . The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months , compared by using a log transformation t test by intention-to-treat analysis . RESULTS The median age of the study patients was 63.5 years , and 39.5 % were women . There were 43 CHF hospital admissions and 7 deaths in the intervention group , as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group ( p = 0.09 ) . The quality -of-life score , percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group . Cost per patient , in 1998 U.S. dollars , was similar in both groups . CONCLUSIONS This study demonstrates that a six-month , multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF BACKGROUND Nursing approaches to manage patients with heart failure ( HF ) showed benefits in reducing the morbidity and mortality . However , combining intra-hospital education with telephone contact after hospital discharge has been little explored . OBJECTIVE To compare two nursing intervention groups among patients hospitalized due to decompensated HF : the intervention group ( IG ) received educational nursing intervention during hospitalization followed by telephone monitoring after discharge and the control group ( CG ) received in-hospital intervention only . Outcomes were levels of HF and self-care knowledge , the frequency of visits to the emergency room , rehospitalizations and deaths in a three-month period . METHODS R and omized clinical trial . We studied adult HF patients with left ventricle ejection fraction ( LVEF ) < 45 % who could be contacted by telephone after discharge . HF awareness was evaluated through a st and ardized question naire that also included questions regarding self-care knowledge , which was answered during the hospitalization period and three months later . For patients in the IG group contacts were made using phone calls and final interviews were conducted in both groups at end of the study . RESULTS Forty-eight patients were assigned to the IG and 63 to the CG . Mean age ( 63 ± 13 years ) and L ( around 29 % ) were similar in the two groups . Scores for HF and self-care knowledge were similar at baseline . Three months later , both groups showed significantly improved HF awareness and self-care knowledge scores ( P < 0.001 ) . Other outcomes were similar . CONCLUSION An in-hospital educational nursing intervention benefitted all HF patients in underst and ing their disease , regardless of telephone contact after discharge Background : home visits and telephone calls are two often used approaches in transitional care but their differential effects are unknown . Objective : to examine the overall effects of a transitional care programme for discharged medical patients and the differential effects of telephone calls only . Design : r and omised controlled trial . Setting : a regional hospital in Hong Kong . Participants : patients discharged from medical units fitting the inclusion criteria ( n = 610 ) were r and omly assigned to : control ( ‘ control ’ , n = 210 ) , home visits with calls ( ‘ home ’ , n = 196 ) and calls only ( ‘ call ’ , n = 204 ) . Intervention : the home groups received alternative home visits and calls and the call groups calls only for 4 weeks . The control group received two placebo calls . The nurse case manager was supported by nursing students in delivering the interventions . Results : the home visit group ( after 4 weeks 10.7 % , after 12 weeks 21.4 % ) and the call group ( 11.8 , 20.6 % ) had lower readmission rates than the control group ( 17.6 , 25.7 % ) . Significance differences were detected in intention-to-treat ( ITT ) analysis for the home and intervention group ( home and call combined ) at 4 weeks . In the per- protocol analysis ( PPA ) results , significant differences were found in all groups at 4 weeks . There was significant improvement in quality of life , self-efficacy and satisfaction in both ITT and PPA for the study groups . Conclusions : this study has found that bundled interventions involving both home visits and calls are more effective in reducing readmissions . Many of the transitional care programmes use all-qualified nurses , and this study reveals that a mixed skills model seems to bring about positive effects as well Remote monitoring ( RM ) of homebound heart failure ( HF ) patients has previously been shown to reduce hospital admissions . We conducted a pilot trial of ambulatory , non-homebound patients recently hospitalized for HF to determine whether RM could be successfully implemented in the ambulatory setting . Eligible patients from Massachusetts General Hospital ( n = 150 ) were r and omized to a control group ( n = 68 ) or to a group that was offered RM ( n = 82 ) . The participants transmitted vital signs data to a nurse who coordinated care with the physician over the course of the 6-month study . Participants in the RM program had a lower all-cause per person readmission rate ( mean = 0.64 , SD ± 0.87 ) compared to the usual care group ( mean = 0.73 , SD ± 1.51 ; P-value = .75 ) although the difference was not statistically significant . HF-related readmission rate was similarly reduced in participants . This pilot study demonstrates that RM can be successfully implemented in non-homebound HF patients and may reduce readmission rates Background . The growing number of patients with congestive heart failure has increased both the pressure on hospital re sources and the need for community management of the condition . Improving hospital-to-home transition for this population is a logical step in responding to current practice guidelines ’ recommendations for coordination and education . Positive outcomes have been reported from trials evaluating multiple interventions , enhanced hospital discharge , and follow-up through the addition of a case management role . The question remains if similar gains could be achieved working with usual hospital and community nurses . Methods . A 12-week , prospect i ve , r and omized controlled trial was conducted of the effect of transitional care on health-related quality of life ( disease-specific and generic measures ) , rates of readmission , and emergency room use . The nurse-led intervention focused on the transition from hospital-to-home and supportive care for self-management 2 weeks after hospital discharge . Results . At 6 weeks after hospital discharge , the overall Minnesota Living with Heart Failure Question naire ( MLHFQ ) score was better among the Transitional Care patients ( 27.2 ± 19.1 SD ) than among the Usual Care patients ( 37.5 ± 20.3 SD;P = 0.002 ) . Similar results were found at 12 weeks postdischarge for the overall MLHFQ and at 6- and 12-weeks postdischarge for the MLHFQ ’s Physical Dimension and Emotional Dimension subscales . Differences in generic quality life , as assessed by the SF-36 Physical component , Mental Component , and General Health subscales , were not significantly different between the Transition and Usual Care groups . At 12 weeks postdischarge , 31 % of the Usual Care patients had been readmitted compared with 23 % of the Transitional Care patients ( P = 0.26 ) , and 46 % of the Usual Care group visited the emergency department compared with 29 % in the Transitional Care group ( & khgr;2 = 4.86 , df 1 , P = 0.03 ) . Conclusions . There were significant improvements in health-related quality of life ( HRQL ) associated with Transitional Care and less use of emergency rooms BACKGROUND Care for elderly persons with disabilities is usually characterized by fragmentation , often leading to more intrusive and expensive forms of care such as hospitalization and institutionalization . There has been increasing interest in the ability of integrated models to improve health , satisfaction , and service utilization outcomes . METHODS A program of integrated care for vulnerable community-dwelling elderly persons ( SIPA [ French acronym for System of Integrated Care for Older Persons ] ) was compared to usual care with a r and omized control trial . SIPA offered community-based care with local agencies responsible for the full range and coordination of community and institutional ( acute and long-term ) health and social services . Primary outcomes were utilization and public costs of institutional and community care . Secondary outcomes included health status , satisfaction with care , caregiver burden , and out-of-pocket expenses . RESULTS Accessibility was increased for health and social home care with increased intensification of home health care . There was a 50 % reduction in hospital alternate level inpatient stays ( " bed blockers " ) but no significant differences in utilization and costs of emergency department , hospital acute inpatient , and nursing home stays . For all study participants , average community costs per person were C dollar 3390 higher in the SIPA group but institutional costs were C dollar 3770 lower with , as hypothesized , no difference in total overall costs per person in the two groups . Satisfaction was increased for SIPA caregivers with no increase in caregiver burden or out-of-pocket costs . As expected , there was no difference in health outcomes . CONCLUSIONS Integrated systems appear to be feasible and have the potential to reduce hospital and nursing home utilization without increasing costs BACKGROUND We examined the effect of a home-based intervention ( HBI ) on readmission and death among " high-risk " patients with congestive heart failure discharged home from acute hospital care . METHODS Hospitalized patients with congestive heart failure and impaired systolic function , intolerance to exercise , and a history of 1 or more hospital admissions for acute heart failure were r and omized to either usual care ( n=48 ) or HBI at 1 week after discharge ( n=49 ) . Home-based intervention comprised a single home visit ( by a nurse and pharmacist ) to optimize medication management , identify early clinical deterioration , and intensify medical follow-up and caregiver vigilance as appropriate . The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge . Secondary end points included duration of hospital stay and overall mortality . RESULTS During follow-up , patients in the HBI group had fewer unplanned readmissions ( 36 vs 63 ; P=.03 ) and fewer out-of-hospital deaths ( 1 vs 5 ; P=.11 ) : 0.8+/-0.9 vs 1.4+/-1.8 ( mean + /- SD ) events per patient assigned to HBI and usual care , respectively ( P=.03 ) . Patients in the HBI group also had fewer days of hospitalization ( 261 vs 452 ; P=.05 ) and fewer total deaths ( 6 vs 12 ; P=.11 ) . Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure ( P=.02 ) . Predictors of unplanned readmission were ( 1 ) 14 days or more of unplanned readmission during the 6 months before study entry ( odds ratio [ OR ] , 5.2 ; 95 % confidence interval [ CI ] , 1.8 - 16.2 ) , ( 2 ) previous admission for acute myocardial ischemia ( OR , 3.3 ; 95 % CI , 1.2 - 9.1 ) , and ( 3 ) an albumin plasma concentration of 38 g/L or less ( OR , 2.4 ; 95 % CI , 1.2 - 6.0 ) . Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission ( OR , 0.4 ; 95 % CI , 0.2 - 1.1 ) . CONCLUSION Among a cohort of high-risk patients with congestive heart failure , HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital OBJECTIVES This study was design ed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided , intensive patient management ( BM ) to multidisciplinary care ( MC ) improves outcome in patients following hospitalization due to heart failure ( HF ) . BACKGROUND Patients hospitalized due to HF experience frequent rehospitalizations and high mortality . METHODS Patients hospitalized due to HF were r and omized to BM , MC , or usual care ( UC ) . Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse . In addition , BM included intensified up-titration of medication by HF specialists in high-risk patients . NT-proBNP was used to define the level of risk and to monitor wall stress . This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance . RESULTS A total of 278 patients were r and omized in 8 Viennese hospitals . After 12 months , the BM group had the highest proportion of antineurohormonal triple-therapy ( difference among all groups ) . Accordingly , BM reduced days of HF hospitalization ( 488 days ) compared with the hospitalization for the MC ( 1,254 days ) and UC ( 1,588 days ) groups ( p < 0.0001 ; significant differences among all groups ) . Using Kaplan-Meier analysis , the first HF rehospitalization ( 28 % ) was lower in the BM versus MC groups ( 40 % ; p = 0.06 ) and the MC versus UC groups ( 61 % ; p = 0.01 ) . Moreover , the combined end point of death or HF rehospitalization was lower in the BM ( 37 % ) than in the MC group ( 50 % ; p < 0.05 ) and in the MC than in the UC group ( 65 % ; p = 0.04 ) . Death rate was similar between the BM ( 22 % ) and MC groups ( 22 % ) , but was lower compared with the UC group ( 39 % ; vs. BM : p < 0.02 ; vs. MC : p < 0.02 ) . CONCLUSIONS Compared with MC alone , additional BM improves clinical outcome in patients after HF hospitalization . ( BNP Guided Care in Addition to Multidisciplinary Care ; NCT00355017 ) BACKGROUND Chronic heart failure ( CHF ) accounts for significant morbidity , mortality and health expenditure . Furthermore , patients with CHF are often on numerous pharmacological agents for their comorbidities . The objective of this study was to determine whether a pharmacist directed home medication review intervention had positive effects on CHF patient outcomes . METHODS A total of 120 patients hospitalised for CHF were r and omised to receive a pharmacist directed post-discharge home medication review ( n = 64 , 53.3 % ) or st and ard care ( n = 56 , 46.7 % ) . Participants were followed for 6 months . Primary outcomes were death , CHF hospitalisation and length of hospital stay . RESULTS There were no between group differences in mortality ( hazard ratio = 1.41 , 0.50 to 3.97 ; P = 0.514 ) or CHF hospitalizations ( incidence rate ratio [ IRR ] = 1.74 95 % CI : 0.85 - 3.60 P = 0.131 ) over the 6 month follow-up period . Days of hospital stay for CHF exacerbations in the 6 month follow-up were significantly greater in the intervention group ( IRR = 2.34 95 % CI : 1.80 - 3.05 P = 0.000 ) . CONCLUSIONS Post-discharge pharmacy directed home medication review appeared to have no effect on mortality and health care utilisation above that achieved with st and ard care . The post-acute management of CHF must be a collaborative multi-disciplinary effort by the health care team as it is the additive effect of interventions that are most effective BACKGROUND Heart failure is a common and important cause of morbidity and mortality . Disease management offers promise in reducing the need for hospitalization and improving quality of life for heart failure patients , but experimental data on the efficacy of such programs are limited . METHODS AND RESULTS A total of 151 patients hospitalized with heart failure were r and omized to usual care or scheduled telephone calls by specially trained nurses promoting self-management and guideline -based therapy as prescribed by primary physicians . Nurses also screened patients for heart failure exacerbations , which they managed with supplemental diuretics or by contacting the primary physician for instructions . Outcomes included time to hospital encounter , mortality , number and cost of hospitalizations , functional status , and satisfaction with care . Intervention patients had a longer time to encounter ( hazard ratio [ HR ] = 0.67 ; 95 % confidence interval [ CI ] 0.47 - 0.96 ; P = .029 ) , hospital readmission ( HR = 0.67 ; CI 0.46 - 0.99 ; P = .045 ) , and heart failure-specific readmission ( HR = 0.62 ; CI 0.38 - 1.03 ; P = .063 ) . The number of admissions , hospital days , and hospital costs were significantly lower during the first 6 months after intervention but not at 1 year . The intervention had little effect on functional status , mortality , and satisfaction with care . CONCLUSION A nurse-administered , telephone-based disease management program delayed subsequent health care encounters , but had minimal impact on other outcomes Background . Hospitalization accounts for 70 % of heart failure ( HF ) costs ; readmission rates at 30 days are 24 % and rise to 50 % by 90 days . Agencies anticipate that telehomecare will provide the close monitoring necessary to prevent HF readmissions . Methods and Results . R and omized controlled trial to compare a telehomecare intervention for patients 55 and older following hospital discharge for HF to usual skilled home care . Primary endpoints were 30- and 60-day all-cause and HF readmission , hospital days , and time to readmission or death . Secondary outcomes were access to care , emergency department ( ED ) use , and satisfaction with care . All-cause readmissions at 30 days ( 16 % versus 19 % ) and over six months ( 46 % versus 52 % ) were lower in the telehomecare group but were not statistically significant . Access to care and satisfaction were significantly higher for the telehomecare patients , including the number of in-person visits and days in home care . Conclusions . Patient acceptance of the technology and current home care policies and processes of care were barriers to gaining clinical effectiveness and efficiency AIMS To determine the effect of an integrated heart failure management programme , involving patient and family , primary and secondary care , on quality of life and death or hospital readmissions in patients with chronic heart failure . METHODS AND RESULTS This trial was a cluster r and omized , controlled trial of integrated primary / secondary care compared with usual care for patients with heart failure . The intervention involved clinical review at a hospital-based heart failure clinic early after discharge , individual and group education sessions , a personal diary to record medication and body weight , information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic . Follow-up was for 12 months . One hundred and ninety-seven patients admitted to Auckl and Hospital with an episode of heart failure were enrolled in the study . There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission . The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group ( -11.1 vs -5.8 respectively , 2 P=0.015 ) . The main effect of the intervention was attributable to the prevention of multiple admissions ( 56 intervention group vs 95 control group , 2 P=0.015 ) and associated reduction in bed days . CONCLUSIONS This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days BACKGROUND Despite the availability of proven therapies , outcomes in patients with heart failure ( HF ) remain poor . In this 2-stage , multicenter trial , we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF . METHODS AND RESULTS In Stage 1 , a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme ( ACE ) inhibitors and other HF medications . Before discharge ( Stage 2 ) , patients were r and omized to a patient support program ( PSP ) ( education about HF , self-monitoring , adherence aids , newsletters , telephone hotline , and follow-up at 2 weeks , then monthly for 6 months after discharge ) or usual care . In Stage 1 ( 766 patients ) ACE inhibitor use increased from 58 % on admission to 83 % at discharge ( P < .0001 ) , and the daily dose ( in enalapril equivalents ) increased from 11.3 + /- 8.8 mg to 14.5 + /- 8.8 mg ( P < .0001 ) . In Stage 2 ( 276 patients ) there was no difference in ACE inhibitor adherence , but a reduction in cardiovascular-related emergency room visits ( 49 versus 20 , P = .030 ) , hospitalization days ( 812 versus 341 , P = .003 ) , and cost of care ( 2,531 Canadian dollars less per patient ) in favor of the PSP . CONCLUSION Simple interventions can improve ACE inhibitor use and patient outcomes BACKGROUND Few studies have examined the potential benefits of specialist nurse-led programs of care involving home and clinic-based follow-up to optimise the post-discharge management of chronic heart failure ( CHF ) . OBJECTIVE To determine the effectiveness of a hybrid program of clinic plus home-based intervention ( C+HBI ) in reducing recurrent hospitalisation in CHF patients . METHODS CHF patients with evidence of left ventricular systolic dysfunction admitted to two hospitals in Northern Engl and were assigned to a C+HBI lasting 6 months post-discharge ( n=58 ) or to usual , post-discharge care ( UC : n=48 ) via a cluster r and omization protocol . The co- primary endpoints were death or unplanned readmission ( event-free survival ) and rate of recurrent , all-cause readmission within 6 months of hospital discharge . RESULTS During study follow-up , more UC patients had an unplanned readmission for any cause ( 44 % vs. 22 % : P=0.019 , OR 1.95 95 % CI 1.10 - 3.48 ) whilst 7 ( 15 % ) versus 5 ( 9 % ) UC and C+HBI patients , respectively , died ( P = NS ) . Overall , 15 ( 26 % ) C+HBI versus 21 ( 44 % ) UC patients experienced a primary endpoint . C+HBI was associated with a non-significant , 45 % reduction in the risk of death or readmission when adjusting for potential confounders ( RR 0.55 , 95 % CI 0.28 - 1.08 : P=0.08 ) . Overall , C+HBI patients accumulated significantly fewer unplanned readmissions ( 15 vs. 45 : P<0.01 ) and days of recurrent hospital stay ( 108 vs. 459 days : P<0.01 ) . C+HBI was also associated with greater uptake of beta-blocker therapy ( 56 % vs. 18 % : P<0.001 ) and adherence to Na restrictions ( P<0.05 ) during 6-month follow-up . CONCLUSION This is the first r and omised study to specifically examine the impact of a hybrid , C+HBI program of care on hospital utilisation in patients with CHF . Its beneficial effects on recurrent readmission and event-free survival are consistent with those applying either a home or clinic-based approach BACKGROUND Hospital admissions among patients with congestive heart failure ( CHF ) are a major contributor to health-care costs . Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and result ant readmission . METHODS Chronic CHF patients discharged home after acute hospital admission were r and omly assigned usual care ( n=100 ) or a multidisciplinary , home-based intervention ( n=100 ) , consisting of a home visit by a cardiac nurse 7 - 14 days after discharge . The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months . FINDINGS During 6 months ' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group ( p=0.02 ) . More intervention-group than usual-care patients remained event-free ( 38 vs 51 ; p=0.04 ) . Overall , there were fewer unplanned readmissions ( 68 vs 118 ; p=0.03 ) and associated days in hospital ( 460 vs 1173 ; p=0.02 ) among intervention-group patients . Hospital-based costs were Australian $ 490,300 for the intervention group and A$ 922,600 for the usual-care group ( p=0.16 ) ; the mean cost of the intervention was A$ 350 per patient , and other community-based costs were similar for both groups . INTERPRETATION A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs , prolong event-free and total survival , and improve quality of life among patients with chronic CHF OBJECTIVE To study the impact of remote patient monitoring ( RPM ) upon the most frequent diagnosis in hospitalized patients over 65 years of age-heart failure ( HF ) . We examined the effect of RPM on hospital utilization and Medicare costs of HF patients receiving home care . MATERIAL S AND METHODS Two studies were simultaneously conducted : A r and omized and a matched-cohort study . In the r and omized study , 168 subjects were r and omly assigned ( after hospitalization ) to home care utilizing RPM ( live nursing visits and video-based nursing visits ) or to home care receiving live nursing visits only . In the matched-cohort study , 160 subjects receiving home care with RPM ( live nursing visits and video-based nursing visits ) were matched with home care subjects receiving live nursing visits only . RESULTS Regardless of whether outcomes were being analyzed for all subjects ( intention to treat ) or for hospitalized subjects only , hospitalization rates , time to first admission , length of stay , and costs to Medicare did not differ significantly between groups in either study at 30 or 90 days after enrollment . A notable trend , however , emerged across studies : Although time to hospitalization was shorter in the RPM groups than the control groups , RPM groups had lower hospitalization costs . CONCLUSIONS RPM , when utilized in conjunction with a robust management protocol , was not found to significantly differ from live nursing visits in the management of HF in home care . Shorter hospitalization times and lower associated costs may be due to earlier identification of exacerbation . These trends indicate the need for further study Longitudinal case management is an intervention delivered by professional nurses that involves following patients from the inpatient to the outpatient arena . The h and s-on process of day-to-day case management of elderly persons with heart failure is presented . The issues associated with delivering this intervention to this patient population are examined , and implication s for refining the case management process are discussed BACKGROUND / AIM Poor patient underst and ing of their diagnosis and treatment plan can adversely impact clinical outcome following hospital discharge . Discharge summaries are primarily written for the doctor rather than the patient . We determined patient underst and ing of the reasons for hospitalisation , in-hospital tests , treatments and post-discharge recommendations , and whether a brief patient-directed discharge letter ( PADDLE ) delivered during a brief discussion prior to discharge would improve underst and ing . METHODS A prospect i ve r and omised controlled trial was conducted , including 67 hospitalised patients . After a baseline question naire , patients were r and omised to receive the PADDLE letter or usual care . Those receiving the letter had an immediate follow-up question naire . Patient underst and ing was compared with a summary letter written by the treating clinician , using a 5-point Likert scale ranging from none to full underst and ing . A question naire was administered at 3 and 6 months . RESULTS At baseline , patients had almost full underst and ing ( median score 4 ) of reasons for hospitalisation and treatments . However , despite high self- appraisal , patients objective ly had very little underst and ing of tests performed and post-discharge recommendations ( median 2 ) . Those receiving the letter had an immediate increase to almost full underst and ing ( median 4 ) of tests performed ( P < 0.001 ) and to full underst and ing ( median 5 ) of post-discharge recommendations . This increase did not persist at 3 or 6 months . CONCLUSIONS A simple patient-directed letter delivered during a brief discussion improves patient underst and ing of their hospitalisation and post-discharge recommendations , which is otherwise limited . Further evaluation of this brief and well-received intervention is indicated , with the goal of improving patient underst and ing , satisfaction and clinical outcomes 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 AIMS To evaluate the feasibility of a nurse-monitored , outpatient-care program for elderly patients previously hospitalized with chronic heart failure . METHODS AND RESULTS Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a r and omized study to compare the effect of a nurse-monitored , outpatient-care programme aim ing at symptom management , with conventional care . The inclusion criteria were patients classified in New York Heart Association classes III-IV , age 65 years , and eligibility for an outpatient follow-up programme . The total in-hospital population of patients discharged with a heart-failure diagnosis was surveyed . Eighty-nine per cent of all the hospitalized patients ( n=1541 ) were 65 years old . Of these , 69 % ( n=1058 ) were treated in the medical wards which were screened . The study criteria were met by 158 patients ( 15 % ) . No visits to the nurse occurred in 23 cases among the 79 patients r and omized to the structured-care group ( 29 % ) , mainly on account of death or fatigue . The numbers of hospitalizations and hospital days did not differ between the structured-care and the usual-care groups . CONCLUSIONS Given the selection criteria and the outline of the interventions , the outpatient , nurse-monitored , symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe , chronic heart failure , mainly because of the small proportion of eligible patients and the high drop-out rate . Management of these patients would have to be more adjusted to their home situation PRINCIPLES International guidelines for heart failure ( HF ) care recommend the implementation of inter-professional disease management programmes . To date , no such programme has been tested in Switzerl and . The aim of this r and omised controlled trial ( RCT ) was to test the effect on hospitalisation , mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerl and . METHODS Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF . A total of 42 eligible patients were r and omised to an intervention ( n = 22 ) or usual care group ( n = 20 ) . Medical treatment was optimised and lifestyle recommendations were given to all patients . Intervention patients additionally received a home visit by a HF-nurse , followed by 17 telephone calls of decreasing frequency over 12 months , focusing on self-care . Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care . Data were collected at baseline , 3 , 6 , 9 and 12 months . Mixed regression analysis ( quality of life ) was used . Outcome assessment was conducted by research ers blinded to group assignment . RESULTS After 12 months , 22 ( 52 % ) patients had an all-cause re-admission or died . Only 3 patients were hospitalised with HF decompensation . No significant effect of the intervention was found on HF related to quality of life . CONCLUSIONS An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies Objective Heart failure ( HF ) is a major health problem result ing in a high financial burden for the healthcare system . Many previous HF management programmes reduced adverse clinical outcomes and costs , but they usually involved several professional figures as well as huge investments , requiring re sources and budgets not often available in our healthcare system . We evaluated the effects of our HF management programme , which included patient education and regular outpatient contact with the HF team , on re-hospitalisation and death , optimising the few re sources already available at our hospital . Methods Two hundred consecutive patients admitted to the internal medicine department with a diagnosis of HF were r and omised to the intervention group ( nurse-led education programme , facilitated telephone communication and follow-up visits with an internist at 15 days , 1 and 6 months ) or to the usual care group ( follow-up by their primary care physician ) . The primary endpoints were all-cause readmissions and all-cause deaths during the 6-month post-discharge period . Results There were 81 all-cause hospital readmissions in the intervention group and 82 in the control group ( P = NS ) . Fourteen patients ( 14 % ) in the intervention group and eight patients ( 8 % ) in the control group died during the study period ( P = NS ) . Unplanned outpatient visits were less frequent in the intervention group than in the control group ( 39 [ 28 % ] versus 99 [ 72 % ] , P < 0.001 ) . Conclusions The present low-cost HF management programme reduced unplanned outpatient visits but proved ineffective in reducing subsequent readmissions and in improving clinical status . More intense follow-up monitoring and more re sources are needed to achieve better results Objective To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure . Design Prospect i ve , r and omised trial . Setting University hospital with a primary catchment area of 250 000 inhabitants . Patients 190 patients ( aged 65–84 years , 52.3 % men ) hospitalised because of heart failure . Intervention Two types of patient management were compared . The intervention group received education on heart failure and self management , with follow up at an easy access , nurse directed outpatient clinic for one year after discharge . The control group was managed according to routine clinical practice . Main outcome measures Time to readmission , days in hospital , and health care costs during one year . Results The one year survival rate was 71.8 % ( n = 79 ) in the control group and 70.0 % ( n = 56 ) in the intervention group ( NS ) . The mean time to readmission was longer in the intervention group than in the control group ( 141 ( 87 ) v106 ( 101 ) ; p < 0.05 ) and number of days in hospital tended to be fewer ( 4.2 ( 7.8 ) v 8.2 ( 14.3 ) ; p = 0.07 ) . There was a trend towards a mean annual reduction in health care costs per patient of US$ 1300 ( US$ 1 = SEK 7.76 ) in the intervention group compared with costs in the controls ( US$ 3594 v 2294 ; p = 0.07 ) . Conclusions A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission BACKGROUND Disease management is effective in the general population , but it has not been tested prospect ively in a sample of solely Hispanics with heart failure ( HF ) . We tested the effectiveness of telephone case management in decreasing hospitalizations and improving health-related quality of life ( HRQL ) and depression in Hispanics of Mexican origin with HF . METHODS AND RESULTS Hospitalized Hispanics with chronic HF ( n = 134 ) were enrolled and r and omized to intervention ( n = 69 ) or usual care ( n = 65 ) . The sample was elderly ( 72 + /- 11 years ) , New York Heart Association class III/IV ( 81.3 % ) , and poorly educated ( 78.4 % less than high school education ) . Most ( 55 % ) were unacculturated into US society . Bilingual/bicultural Mexican-American registered nurses provided 6 months of st and ardized telephone case management . Data on hospitalizations were collected from automated systems at 1 , 3 , and 6 months after the index hospital discharge . Health-related quality of life and depression were measured by self-report at enrollment , 3 , and 6 months . Intention to treat analysis was used . No significant group differences were found in HF hospitalizations , the primary outcome variable ( usual care : 0.49 + /- 0.81 [ CI 0.25 - 0.73 ] ; intervention : 0.55 + /- 1.1 [ CI 0.32 - 0.78 ] at 6 months ) . No significant group differences were found in HF readmission rate , HF days in the hospital , HF cost of care , all-cause hospitalizations or cost , mortality , HRQL , or depression . CONCLUSION These results have important implication s because of the current widespread enthusiasm for disease management . Although disease management is effective in the mainstream HF patient population , in Hispanics this ill , elderly , and poorly educated , a different approach may be needed AIMS Heart failure chiefly affects the elderly , with frequent emergency admissions . Telemonitoring can identify worsening heart failure but previous r and omized trials have enrolled selected patient population s. The Home-HF study examined the impact of home telemonitoring on typical heart failure patients discharged from three acute hospitals in North West London , UK . METHODS AND RESULTS Patients hospitalized with heart failure were r and omized to telemonitoring or usual specialist care . Primary outcome measures were days alive and out of hospital . Secondary outcome measures were number and duration of heart failure hospitalizations , clinic visits , and quality of life . We recruited 182 patients . There was no difference in the primary outcome measure in the two groups , but there were significantly fewer unplanned hospitalizations for heart failure decompensation , and a reduction in clinic and emergency room visits in the telemonitoring group . There was no statistically significant difference in the mean direct health service costs . CONCLUSION Home telemonitoring in a typical elderly population of heart failure patients produces a similar outcome to ' usual ' specialist care , but reduces clinic and emergency room visits and unplanned heart failure rehospitalizations at little additional cost . This method of disease monitoring may allow specialist services to increase the number of patients under their care Background — Trials investigating efficacy of disease management programs ( DMP ) in heart failure reported contradictory results . Features rendering specific interventions successful are often ill defined . We evaluated the mode of action and effects of a nurse-coordinated DMP ( HeartNetCare-HF , HNC ) . Methods and Results — Patients hospitalized for systolic heart failure were r and omly assigned to HNC or usual care ( UC ) . Besides telephone-based monitoring and education , HNC addressed individual problems raised by patients , pursued networking of health care providers and provided training for caregivers . End points were time to death or rehospitalization ( combined primary ) , heart failure symptoms , and quality of life ( SF-36 ) . Of 1007 consecutive patients , 715 were r and omly assigned ( HNC : n=352 ; UC : n=363 ; age , 69±12 years ; 29 % female ; 40 % New York Heart Association class III-IV ) . Within 180 days , 130 HNC and 137 UC patients reached the primary end point ( hazard ratio , 1.02 ; 95 % confidence interval , 0.81–1.30 ; P=0.89 ) , since more HNC patients were readmitted . Overall , 32 HNC and 52 UC patients died ( 1 UC patient and 4 HNC patients after dropout ) ; thus , uncensored hazard ratio was 0.62 ( 0.40–0.96 ; P=0.03 ) . HNC patients improved more regarding New York Heart Association class ( P=0.05 ) , physical functioning ( P=0.03 ) , and physical health component ( P=0.03 ) . Except for HNC , health care utilization was comparable between groups . However , HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure – related issues . Conclusions — The primary end point of this study was neutral . However , mortality risk and surrogates of well-being improved significantly . Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N23325295 BACKGROUND Both r and omized and nonr and omized controlled studies have linked congestive heart failure ( CHF ) case management ( CM ) to decreased readmissions and improved outcomes in mostly homogeneous setting s. The objective of this r and omized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting . METHODS A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF , left ventricular dysfunction of less than 40 % , or radiologic evidence of pulmonary edema for which they underwent diuresis were r and omized . The intervention consisted of 4 major components : early discharge planning , patient and family CHF education , 12 weeks of telephone follow-up , and promotion of optimal CHF medications . RESULTS The 90-day readmission rates were equal for the CM and usual care groups ( 37 % ) . Total inpatient and outpatient median costs and readmission median cost were reduced 14 % and 26 % , respectively , for the intervention group . Patients in the CM group were more likely to be taking CHF medication at target doses , but dosages did not increase significantly throughout 12 weeks . Although both groups took their medications as prescribed equally well , the rest of the adherence to treatment plan was significantly better in the CM group . Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group ( P = .03 ) . CONCLUSIONS These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting . One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended , nonnetworked physician setting limits the effectiveness of the CM OBJECTIVES To examine the effectiveness of a transitional care intervention delivered by advanced practice nurses ( APNs ) to elders hospitalized with heart failure . DESIGN R and omized , controlled trial with follow-up through 52 weeks postindex hospital discharge . SETTING Six Philadelphia academic and community hospitals . PARTICIPANTS Two hundred thirty-nine eligible patients were aged 65 and older and hospitalized with heart failure . INTERVENTION A 3-month APN-directed discharge planning and home follow-up protocol . MEASUREMENTS Time to first rehospitalization or death , number of rehospitalizations , quality of life , functional status , costs , and satisfaction with care . RESULTS Mean age of patients ( control n=121 ; intervention n=118 ) enrolled was 76 ; 43 % were male , and 36 % were African American . Time to first readmission or death was longer in intervention patients ( log rank chi(2)=5.0 , P=.026 ; Cox regression incidence density ratio=1.65 , 95 % confidence interval=1.13 - 2.40 ) . At 52 weeks , intervention group patients had fewer readmissions ( 104 vs 162 , P=.047 ) and lower mean total costs ( $ 7,636 vs $ 12,481 , P=.002 ) . For intervention patients , only short-term improvements were demonstrated in overall quality of life ( 12 weeks , P<.05 ) , physical dimension of quality of life ( 2 weeks , P<.01 ; 12 weeks , P<.05 ) and patient satisfaction ( assessed at 2 and 6 weeks , P<.001 ) . CONCLUSION A comprehensive transitional care intervention for elders hospitalized with heart failure increased the length of time between hospital discharge and readmission or death , reduced total number of rehospitalizations , and decreased healthcare costs , thus demonstrating great promise for improving clinical and economic outcomes BACKGROUND Congestive heart failure is the most common indication for admission to the hospital among older adults . Behavioral factors , such as poor compliance with treatment , frequently contribute to exacerbations of heart failure , a fact suggesting that many admissions could be prevented . METHODS We conducted a prospect i ve , r and omized trial of the effect of a nurse-directed , multidisciplinary intervention on rates of readmission within 90 days of hospital discharge , quality of life , and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure . The intervention consisted of comprehensive education of the patient and family , a prescribed diet , social-service consultation and planning for an early discharge , a review of medications , and intensive follow-up . RESULTS Survival for 90 days without readmission , the primary outcome measure , was achieved in 91 of the 142 patients in the treatment group , as compared with 75 of the 140 patients in the control group , who received conventional care ( P = 0.09 ) . There were 94 readmissions in the control group and 53 in the treatment group ( risk ratio , 0.56 ; P = 0.02 ) . The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group ( 54 vs. 24 , P = 0.04 ) , whereas the number of readmissions for other causes was reduced by 28.5 percent ( 40 vs. 29 , P not significant ) . In the control group , 23 patients ( 16.4 percent ) had more than one readmission , as compared with 9 patients ( 6.3 percent ) in the treatment group ( risk ratio , 0.39 ; P = 0.01 ) . In a subgroup of 126 patients , quality -of-life scores at 90 days improved more from base line for patients in the treatment group ( P = 0.001 ) . Because of the reduction in hospital admissions , the overall cost of care was $ 460 less per patient in the treatment group . CONCLUSIONS A nurse-directed , multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure BACKGROUND Heart failure ( HF ) disease management programs are widely implemented , but data about their effect on outcome have been inconsistent . METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure ( COACH ) was a multicenter , r and omized , controlled trial in which 1023 patients were enrolled after hospitalization because of HF . Patients were assigned to 1 of 3 groups : a control group ( follow-up by a cardiologist ) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF . Patients were studied for 18 months . Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization . RESULTS Mean patient age was 71 years ; 38 % were women ; and 50 % of patients had mild HF and 50 % had moderate to severe HF . During the study , 411 patients ( 40 % ) were readmitted because of HF or died from any cause : 42 % in the control group , and 41 % and 38 % in the basic and intensive support groups , respectively ( hazard ratio , 0.96 and 0.93 , respectively ; P = .73 and P = .52 , respectively ) . The number of days lost to death or hospitalization was 39 960 in the control group , 33 731 days for the basic intervention group ( P = .81 ) , and 34 268 for the intensive support group ( P = .49 ) . All-cause mortality occurred in 29 % of patients in the control group , and there was a trend toward lower mortality in the intervention groups combined ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.08 ; P = .18 ) . There were slightly more hospitalizations in the 2 intervention groups ( basic intervention group , P = .89 ; and intensive support group , P = .60 ) . CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with st and ard follow-up . There was a nonsignificant , potentially relevant reduction in mortality , accompanied by a slight increase in the number of short hospitalizations in both intervention groups . Clinical Trial Registry http://trialregister.nl Identifier : NCT 98675639 Objective Elderly heart failure patients are at high risk of events . Available studies and systematic review s suggest that elderly patients benefit from disease management programmes ( DMPs ) . However , important questions remain open , including the optimal follow-up intensity and duration and whether such interventions are cost-effective during long-term follow-up and in different healthcare systems . The aim of this study was to determine the long-term efficacy of a hybrid DMP in consecutive older out patients . Methods Intervention consisted in combined hospital-based ( cardiologists and nurse-coordinators from two heart failure clinics ) and home-based ( patient 's general practitioner visits ) care . The components of the DMP were the following : discharge planning , education , therapy optimisation , improved communication , early attention to signs and symptoms . Intensive follow-up was based on scheduled hospital visits ( starting within 14 days of discharge ) , nurse 's phone call and home general practitioner visits . Results A group of 173 patients aged ≥70 years ( mean age 77 ± 6 years , 48 % women ) was r and omly assigned to DMP ( n = 86 ) or usual care ( n = 87 ) . At 2-year follow-up , a 36 % reduction in all-cause death and heart failure hospital admissions was observed in DMP vs. usual care . All-cause and heart failure admissions as well as the length of hospital stay were also reduced . DMP patients reported , compared to baseline , significant improvements in functional status , quality of life and β-blocker prescription rate . The intervention was cost-effective with a mean saving of & U20AC ; 982.04 per patient enrolled . Conclusions A hybrid DMP for elderly heart failure patients improves outcomes and is cost-effective over a long-term follow-up Previous studies have found that home-based intervention programs reduce readmission rates for patients with heart failure . Only one previous trial has compared telephone and videophone to traditional care to deliver a home-based heart failure intervention program . The objective of this study was to evaluate the efficacy of a telehealth-facilitated postdischarge support program in reducing re source use in patients with heart failure . Patients at a Midwestern Department of Veterans Affairs Medical Center were r and omized to telephone , videophone , or usual care for follow-up care after hospitalization for heart failure exacerbation . Outcome measures included readmission rates ; time to first readmission ; urgent care clinic visits ; survival ; and quality of life . The intervention result ed in a significantly longer time to readmission but had no effect on readmission rates or mortality . There were no differences in hospital days or urgent care clinic use . All subjects reported higher disease-specific quality of life scores at 1 year . There was evidence of the value of telephone follow-up , but there was no evidence to support the benefit of videophone care over telephone care . Rigorous evaluation is needed to determine which patients may benefit most from specific telehealth applications and which technologies are most cost-effective Background : Although multidisciplinary congestive heart failure clinics in the United States appear to be effective in reducing the number of hospital readmissions , it is unclear whether the same benefit is seen in countries such as Canada , where access to both general and specialized medical care is free and unrestricted . We sought to determine the impact of care at a multidisciplinary specialized outpatient congestive heart failure clinic compared with st and ard care . Methods : We r and omly assigned 230 eligible patients who had experienced an acute episode of congestive heart failure to st and ard care ( n = 115 ) or follow-up at a multidisciplinary specialized heart failure outpatient clinic ( n = 115 ) . The intervention consisted of a structured outpatient clinic environment with complete access to cardiologists and allied health professionals . The primary outcomes were all-cause hospital admission rates and total number of days in hospital at 6 months . The secondary outcomes were total number of emergency department visits , quality of life and total mortality . Results : At 6 months , fewer patients in the intervention group had required readmission to hospital than patients in the control group ( 45 [ 39 % ] v. 66 [ 57 % ] , crude hazard ratio [ HR ] 0.59 , 95 % confidence interval [ CI ] 0.38–0.92 . Patients in the intervention group stayed in hospital for 514 days compared with 815 days required by patients in the control group ( adjusted HR 0.56 , 95 % CI 0.35–0.89 ) . The number of patients seen in the emergency department and the total number of emergency department visits were similar in the intervention and control groups . At 6 months , quality of life , which was self-assessed using the Minnesota Living with Heart Failure question naire , was unchanged in the control group but improved in the intervention group ( p < 0.001 ) . No difference in mortality was observed , with 19 deaths in the control group and 12 in the intervention group ( HR 0.61 , 95 % CI 0.24–1.54 ) . Interpretation : Compared with usual care , care at a multidisciplinary specialized congestive heart failure outpatient clinic reduced the number of hospital readmissions and hospital days and improved quality of life . When our results are integrated with those from other , similar trials , multidisciplinary disease management strategies for congestive heart failure are associated with clinical ly worthwhile improvements in survival AIMS AND OBJECTIVES To evaluate the effectiveness and cost-effectiveness of a community nurse-supported hospital discharge programme in preventing hospital re-admissions , improving functional status and h and icap of older patients with chronic heart failure . DESIGN R and omized controlled trial ; 105 hospitalized patients aged 60 years or over with chronic heart failure and history of hospital admission(s ) in previous year were r and omly assigned into intervention group ( n = 49 ) and control group ( n = 56 ) for six months . Intervention group subjects received community nurse visits before discharge , within seven days of discharge , weekly for four weeks , then monthly . Community nurse liaised closely with a design ated specialist in hospital and were accessible to subjects during normal working hours . Control and intervention group subjects were followed up in the same specialist medical clinics . Primary outcome was the rate of unplanned re-admission at six months . Secondary outcomes were number of unplanned re-admissions , six-minute walking distance , London H and icap Scale and public health care and personal care costs . RESULTS At sixth months , the re-admission rates were not significantly different ( 46 vs. 57 % in control subjects , p = 0.233 , Chi-square test ) . But the median number of re-admissions tended to lower in the intervention group ( 0 vs. 1 in control group , p = 0.057 , Mann Whitney test ) . Intervention group subjects had less h and icap in independence ( median change 0 vs. 0.5 in control subjects , p = 0.002 , Mann Whitney test ) , but there was no difference in six-minute walking distance . There was no significant group difference in median total public health care and personal care costs . CONCLUSION Community nurse-supported post-discharge programme was effective in preserving independence and was probably effective in reducing the number of unplanned re-admissions . The cost benefits to public health care were not significant . RELEVANCE TO CLINICAL PRACTICE Older chronic heart failure patients are likely to benefit from post-discharge community nurse intervention programmes . More comprehensive health economic evaluation needs to be undertaken AIMS Disease management programs can reduce hospitalizations in high-risk heart failure ( HF ) patients , but generalizability to the population hospitalized for HF remains to be proven . We aim ed to assess the effectiveness of a discharge and outpatient management program in a non-selected cohort of patients hospitalized for HF . METHODS AND RESULTS Patients admitted with decompensated HF were r and omized to receive usual care ( n=174 ) or an intervention ( n=164 ) consisting of a comprehensive hospital discharge planning and close follow-up at a HF clinic . After a median of 509 days , there were fewer events ( readmission or death ) in the intervention as compared with the control group ( 156 vs. 250 ) , which represents 47 % ( 95%CI : 29 - 65 ; P<0.001 ) event reduction per observation year . At 1-year , time to first event , time to first all-cause and HF readmission , and time to death were increased in the intervention group ( P<0.001 ) . All-cause and HF readmission rates per observation year were significantly lower , quality of life improved and overall cost of care was reduced in the intervention group . CONCLUSIONS This comprehensive hospital discharge and outpatient management program prolonged time to first event , reduced hospital readmissions , improved survival and quality of life of patients hospitalized for HF , while reducing cost of management Background Atrial fibrillation ( AF ) , the most common chronic cardiac dysrhythmia , is an important cause of cardiovascular morbidity and mortality . However , there is a paucity of studies examining the potential benefits of optimizing the postdischarge management of patients with chronic AF . Research objective To examine the effects of a nurse-led , multidisciplinary , home-based intervention ( HBI ) on the pattern of recurrent hospitalization and mortality in patients with chronic AF in the presence and absence of chronic heart failure ( HF ) . Patient cohort and methods Health outcomes in a total of 152 hospitalized patients ( 53 % male ) with a mean age of 73±9 years and a diagnosis of chronic AF who were r and omly allocated to either HBI ( n = 68 ) or usual postdischarge care ( UC : n = 84 ) were examined . Specifically , the pattern of unplanned hospitalization and all-cause mortality during 5-year follow-up were compared on the basis of the presence ( n = 87 ) and absence ( n = 65 ) of HF at baseline . Results Patients with concurrent HF exposed to HBI ( n = 37 ) had fewer readmissions ( 2.9 vs 3.4/patient ) , days of associated hospital stay ( 22.7 vs 30.5 : P = NS ) and fatal events ( 51 % vs 66 % ) relative to UC ( n = 50 ) : P = NS for all comparisons . In the absence of HF , morbidity and mortality rates were significantly lower but still substantial during 5-year follow-up . In these patients , HBI was associated with a trend towards prolonged event-free survival ( adjusted RR = 0.70 ; P = .12 ) and fewer fatal events ( 29 % vs 53 % , adjusted RR = 0.49 ; P = .08 ) . HBI patients ( n = 31 ) also had fewer readmissions ( 2.1 vs 2.6/patient ) and days of associated hospital stay ( 16.3 vs 20.3/patient ) , although this did not reach statistical significance . On the basis of these data , it was calculated that a r and omized study of an AF-specific HBI would require 250 patients followed for a median of 3 years to detect a 25 % variation in recurrent hospital stay relative to UC . Conclusions These unique data provide sufficient preliminary evidence to support the hypothesis that the benefits of HBI in relation to the management of HF may extend to “ high risk ” patients with chronic AF in whom morbidity and mortality rates are also unacceptably high . Further , appropriately powered studies are required to confirm these benefits BACKGROUND Chronic heart failure ( CHF ) remains a common cause of disability , death and hospital admission . Several investigations support the usefulness of programs of disease management for improving clinical outcomes . However , the effect of home-based telemanagement programs on the rate of hospital readmission is still unclear and the cost-effectiveness ratio of such programs is unknown . The aim of the study was to determine whether a home-based telemanagement ( HBT ) programme in CHF patients decreased hospital readmissions and hospital costs in comparison with the usual care ( UC ) follow-up programme over a one-year period . METHODS AND RESULTS Four hundred-sixty CHF patients ( pts ) , aged 57+/-10 years were r and omised to two management strategies : 230 pts to HBT programme and 230 pts to UC programme . The HBT pts received a portable device , transferring , by telephone , a one-lead trace to a receiving station where a nurse was available for interactive teleconsultation . The UC pts were referred to their primary care physicians and cardiologists . The primary objective of the study was one-year hospital readmission for cardiovascular reasons . During one-year follow-up 55 pts ( 24 % ) in HBT group and 83 pts ( 36 % ) in UC group had at least one readmission ( RR=0.56 ; 95 % CI : 0.38 - 0.82 ; p=0.01 ) . After adjusting for clinical and demographic characteristics , the HBT group had a significantly lower risk of readmission compared with the UC group ( HR=0.50 , 95 % CI : 0.34 - 0.73 ; p=0.01 ) . The intervention was associated with a 36 % decrease in the total number of hospital readmissions ( HBT group : 91 readmissions ; UC group : 142 readmissions ) and a 31 % decrease in the total number of episodes of hemodynamic instability ( 101 in HBT group vs 147 in UC group ) . The rate of hearth failure-related readmission was 19 % ( 43 pts ) in HBT group and 32 % ( 73 pts ) in UC group ( RR=0.49 , 95 % [ CI ] : 0.31 - 0.76 ; p=0.0001 ) . No significant difference was found on cardiovascular mortality between groups . Mean cost for hospital readmission was significantly lower in HBT group ( euro 843+/-1733 ) than in UC group ( euro 1298+/-2322 ) , ( -35 % , p<0.01 ) . CONCLUSIONS This study suggests that one-year HBT programme reduce hospital readmissions and costs in CHF patients BACKGROUND Heart failure management programmes have been shown to reduce re-hospitalizations . We recently investigated a new disease management programme comparing usual care ( UC ) to home-based nurse care ( HNC ) and a HNC group in which decision-making was based on NT-proBNP levels ( BNC ) . As re-hospitalization is the main contributing economic factor in heart failure expenditures , we hypothesized that this programme might be able to reduce costs and could be conducted cost effectively compared to UC . METHODS One hundred and ninety congestive heart failure patients , who were included in a r and omized trial to receive UC , HNC or BNC at discharge , were analysed in a cost-effectiveness model . Different models were applied to perform analysis of all medical costs , and the costs per year survived were chosen as an effectiveness parameter . RESULTS Per patient costs because of heart failure treatment in the UC and the BNC group were € 7109 ± 11,687 and € 2991 ± 4885 ( P=0·027 ) , respectively . Corrected for death as a competing risk , the costs in the UC group were € 7893 ± 11,734 and were reduced by BNC to € 3148 ± 4949 ( P=0·012 ) . Considering costs because of all-cause re-hospitalizations , calculated costs per year survived after discharge were € 19,694 ± 26,754 for UC , € 14,262 ± 25 330 for HNC ( P > 0·05 ) and € 8784 ± 14,728 for BNC ( t-test-based contrast P=0·015 ) . In all models calculated , HNC was cost neutral . CONCLUSIONS NT-BNP-guided heart failure specialist care in addition to home-based nurse care is cost effective and cheaper than st and ard care , whereas HNC is cost neutral |
11,290 | 24,590,672 | AUTHORS ' CONCLUSIONS Based on the trials identified in this review , there is uncertainty as to which type of IOL provides the best visual and clinical outcomes in people with uveitis undergoing cataract surgery .
However , due to small sample sizes and heterogeneity in outcome reporting , we found insufficient information to assess these and other types of IOL material s for cataract surgery for eyes with uveitis | BACKGROUND Cataract formation often occurs in people with uveitis .
It is unclear which intraocular lens ( IOL ) type is optimal for use in cataract surgery for eyes with uveitis .
OBJECTIVES To summarize the effects of different IOLs on visual acuity , other visual outcomes , and quality of life in people with uveitis . | Purpose : To compare the course of inflammation after small‐incision cataract surgery with implantation of 1 of 3 types of foldable intraocular lenses ( IOLs ) in eyes with uveitis . Setting : Department of Ophthalmology , University of Vienna , Vienna , Austria . Methods : Seventy‐four eyes with uveitis and cataract and 68 control eyes with cataract were prospect ively selected to receive a foldable hydrophilic acrylic ( Hydroview ® , Bausch & Lomb ) , hydrophobic acrylic ( AcrySof ® , Alcon ) , or silicone ( CeeOn ® 911 , Pharmacia ) IOL . All surgery was performed by the same surgeon using a st and ardized protocol : clear corneal incision , capsulorhexis , phacoemulsification , and in‐the‐bag IOL implantation . Preoperative and postoperative inflammation was evaluated by measuring aqueous flare preoperatively and 1 , 3 , 7 , 28 , 90 , and 180 days after surgery using the Kowa FC‐1000 ® laser flare‐cell meter . All uveitic eyes were in remission for at least 3 months before surgery . Results : In the uveitic eyes , there was no statistically significant difference in the postoperative course of flare and cell among the 3 IOL groups . Six months after surgery in uveitic eyes , flare values reached preoperative levels and the cell count was lower than preoperatively in all 3 IOL groups . Relative flare values were higher in the eyes with uveitis and a CeeOn 911 IOL ; however , the difference between this group and the 2 acrylic IOL groups was not significant . Conclusions : There were no significant differences in inflammation after implantation of foldable IOLs in uveitic eyes . Although absolute flare values and cell counts in eyes with uveitis were higher than in control eyes , primarily because of a damaged blood‐aqueous barrier ( BAB ) , BAB recovery was similar between the 2 groups . The changes in the BAB indicate that foldable IOL implantation is safe in uveitic eyes Purpose : To evaluate the postoperative outcomes in uveitic eyes after phacoemulsification and posterior chamber intraocular lens ( IOL ) implantation . Setting : Multicenter ( 19 ) international study . Methods : This prospect i ve r and omized comparative interventional case series comprised 140 eyes of 140 patients who had phacoemulsification and implantation of IOLs of various material s : hydrophobic acrylic ( n = 48 ) , silicone ( n = 44 ) , poly(methyl methacrylate ) ( PMMA ) ( n = 26 ) , or heparin‐surface‐modified PMMA ( HSM PMMA ) ( n = 22 ) . Preoperative and postoperative grading and control of intraocular inflammation were performed . Clinical ly significant observations , visual outcomes , and the incidence of postoperative complications were recorded . Results : At the final follow‐up , 64 eyes ( 46.3 % ) had a best corrected visual acuity of 20/40 or better , an improvement that was highly significant ( P < .0001 ) . One day after surgery , the acrylic group had the lowest inflammation values and the silicone group the highest ( P = .02 ) . The acrylic group continued to have the lowest inflammation grade values until the 3‐month follow‐up . The acrylic and HSM PMMA groups had the lowest incidence of relapses . Posterior capsule opacification developed in 48 eyes ( 34.2 % ) , with the highest incidence in the silicone group . Conclusions : Phacoemulsification with IOL implantation in selected uveitic eyes was safe and effective . Acrylic IOLs provided a better visual outcome and lower complication rate than IOLs of other material Background To compare a hydrophobic and a hydrophilic acrylic single-piece intraocular lens ( IOL ) in uveitis patients with respect to biocompatibility and visual outcome . Methods Prospect i ve , r and omized study in patients with noninfectious uveitis after phacoemulsification and implantation of either a hydrophobic AcrySof ™ ( group 1 , n = 30 ) or a hydrophilic Akreos adapt ™ ( group 2 , n = 30 ) , sharp-edged acrylic IOL . The primary outcome was uveal biocompatibility , detected by giant-cell deposition , anterior chamber cell count and laserflare photometry over a 6-month follow-up period . Secondary outcome measures were capsular biocompatibility , as detected by posterior capsule opacification ( PCO ) , lens epithelial cell outgrowth and Nd : YAG capsulotomies , and visual outcome . Results The groups did not differ with respect to anatomic type of uveitis , immunosuppressive treatment , associated systemic disease , and intraoperative manipulation . The number of giant cells on the anterior IOL surface was higher in group 1 than in group 2 ( p = 0.03 ) . The number of anterior chamber cells , laser flare photometry levels , and uveitis reactivations after surgery did not differ between the groups . After 6 months , the number of patients with PCO development ( p = 1.0 ) and Nd : YAG capsulotomies ( p = 0.21 ) , lens epithelial cell outgrowth , visual outcome and uveitis complications were comparable in both groups . Conclusions Both of the acrylic IOLs used had good uveal and capsular biocompatibility , leading to significant improvement in BCVA in patients with noninfectious uveitis . No obvious differences were detected at 6 months with respect to uveal and capsular biocompatibility and visual outcome OBJECTIVE To assess the outcome of cataract surgery in eyes of patients with uveitis . DESIGN Prospect i ve , noncomparative case series . PARTICIPANTS A total of 90 eyes of 76 patients fulfilled the enrollment criteria . INTERVENTION All patients had their surgery performed using st and ard cataract extraction techniques . Unless contraindicated , preoperative systemic steroids were administered to all patients with posterior disease , chronic anterior uveitis , with known macular edema , and those in whom outcome of cataract surgery on the fellow eye had been poor . RESULTS Patients were divided into those with anterior disease ( n = 53 ) and those with posterior disease ( n = 37 ) . Overall , 81 ( 90 % ) of 90 eyes showed improvement in vision ( median + 4 Snellen lines ) . In those with anterior disease , the development of severe uveitis in the first week postsurgery was associated with a greater incidence of macular edema ( P = 0.014 ) . The single largest diagnosis in those with posterior disease was that of panuveitis ( n = 24 ) . This group showed the poorest visual outcomes in this study . The majority of patients , however , were noted to have visual loss secondary to conditions present before surgery . CONCLUSION Cataract surgery in eyes with uveitis leads to an improvement of vision in the majority of cases . Severe postoperative uveitis is the most common postoperative complication and is associated with a significant risk of macular edema in those with anterior disease . In the posterior group , poor visual outcome after surgery is most commonly the result of preoperative vision-limiting conditions Purpose To compare the clinical results of heparin surface modified ( HSM ) hydrophilic acrylic intraocular lens ( IOL ) with those of hydrophobic acrylic IOL . Methods One hundred patients with cataract were r and omized to receive one of acrylic foldable IOLs after phacoemulsification : HSM hydrophilic acrylic IOL ( n=50 ) BioVue3 ® ( BioVue , OII , Ontario , CA , USA ) and hydrophobic acrylic IOL ( n=50 ) Sensar ® ( AR40e , AMO , Santa Ana , CA , USA ) . Best-corrected visual acuity and refractive error were measured at 1 week , 2 months , 6 months and 12 months after surgery in both IOL groups . To assess posterior capsular opacification ( PCO ) , digital retroillumination image of posterior capsule was analyzed at 12 months using POCOman software . Results Best-corrected visual acuity ( log MAR ) was 0.032±0.082 in BioVue3 ® group and 0.034±0.077 in Sensar ® group at 12 months . There was no statistically significant difference between the two groups ( p=0.554 ) . Refractive error was −0.247±0.821 diopter in BioVue3 ® group and −0.264±0.808 diopter in Sensar ® group at 12 months . There was no statistically significant difference of refractive error between the two groups ( p=0.909 ) . At 12 months , BioVue3 ® IOL group had a lower percentage area and severity of PCO than Sensar ® group . However , it was not statistically significant ( p=0.349 , p=0.288 ) . No Nd : YAG capsulotomy was performed in BioVue3 ® group while it was required in two eyes ( 4.0 % ) in Sensar ® group . Conclusions There was no statistically significant difference of postoperative visual acuity , refractive error and degree of PCO between HSM hydrophilic acrylic IOL and hydrophobic acrylic IOL Purpose . To evaluate various available intraocular lenses ( IOL ) ( PMMA , acrylic , heparin coated PMMA , and silicone ) in patients with cataracta complicata and evaluate IOL tolerance , post-operative inflammation , cystoid macular edema , and posterior capsular opacification(PCO ) requiring Nd : YAG capsulotomy . Design . r and omized , double masked clinical trial . Participants . Patients evaluated in the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary and deemed to need cataract surgery by st and ard criteria were asked to participate in the clinical trial . Patients had to have a diagnosis of chronic uveitis , which was inactive for 3 months prior to cataract surgery . Results . Acrylic lenses appeared to provide the best overall results when evaluated for post-operative inflammation , PCO rates , visual acuity , and cystoid macular edema ( CME ) ( compared to PMMA , silicone , and heparin coated PMMA ) Purpose : To evaluate the uveal and capsular biocompatibility of hydrophilic acrylic , hydrophobic acrylic , and silicone intraocular lenses ( IOLs ) in eyes with uveitis . Setting : Department of Ophthalmology , University of Vienna , Vienna , Austria . Methods : This prospect i ve study comprised 72 eyes with uveitis and 68 control eyes having phacoemulsification and IOL implantation by 1 surgeon . Patients received 1 of the following IOLs : foldable hydrophilic acrylic ( Hydroview ® , Bausch & Lomb ) , hydrophobic acrylic ( AcrySof ® , Alcon ) , or silicone ( CeeOn ® 911 , Pharmacia ) . Postoperative evaluations were at 1 , 3 , and 7 days and 1 , 3 , and 6 months . Cell reaction was evaluated by specular microscopy of the anterior IOL surface and the anterior and posterior capsule reaction , by biomicroscopy . Results : Small round cell deposition was observed on all IOLs in the immediate postoperative period , especially in eyes with uveitis . This reaction decreased 3 to 6 months after surgery . Although the CeeOn 911 had a higher mean grade of small cells , there was no statistical difference between the 3 IOL types after 6 months in the uveitis and control groups . Foreign‐body giant cells ( FBGCs ) increased after 1 week to 1 month . The AcrySof IOLs had the highest number of FBGCs ; after 6 months , there was a statistically significant difference between the AcrySof and Hydroview uveitis groups ( P = .036 ) and the AcrySof and CeeOn 911 uveitis groups ( P = .003 ) but there was no difference among the 3 IOL types in the control group . Lens epithelial cell outgrowth persisted on the Hydroview IOLs in control eyes and regressed on all 3 IOL types in uveitic eyes and on the AcrySof and CeeOn 911 IOLs in control eyes ( P = .0001 ) . Anterior capsule opacification ( ACO ) was more severe on all IOL types in uveitic eyes and on the CeeOn 911 IOL in control eyes . Posterior capsule opacification ( PCO ) was more severe in uveitic eyes . The Hydroview group had more severe PCO than the AcrySof and the CeeOn 911 groups in uveitis and control eyes . Six months postoperatively , the difference was significant ( P = .0001 ) . There was no significant difference between the AcrySof and CeeOn 911 IOLs . Conclusions : Intraocular lens biocompatibility is inversely related to inflammation . Hydrophilic acrylic material had good uveal but worse capsular biocompatibility . Hydrophobic acrylic material had lower uveal but better capsular biocompatibility . Silicone showed a higher small cell count ( mild ) and more severe ACO but achieved PCO results comparable to FBGC results and better than those with the AcrySof lens 6 months after surgery . Despite the differences in IOL biocompatibility , all patients benefited from the surgery PURPOSE A heparin surface modified posterior chamber intraocular lens ( IOL ) was compared with a conventional polymethylmethacrylate ( PMMA ) IOL regarding postoperative complications caused by inflammation . METHODS Five hundred twenty-four patients from 10 different centers were included in a parallel group , double-masked , multicenter study . RESULTS The cumulative number of patients with inflammatory cellular deposits on their IOLs during the first postoperative year differed significantly in favor of the heparin surface modified group , with 29.8 % of the patients having cellular deposits compared with 48.8 % of patients in the control group . Cellular deposits were observed most frequently at 3 months after surgery , and the difference between the groups was most pronounced and statistically significant at this time . The same results were seen at 1 year , but the difference was not significant . The number of cellular deposits per patient , however , was significantly lower in the heparin surface modified group at 1 year . Cumulatively , there were significantly more patients with posterior synechiae in the PMMA group than in the heparin surface modified group during the 1-year follow-up . Complications were few and comparable between the groups . CONCLUSION The results of this study indicate that heparin surface modification reduces the inflammatory response to PMMA IOLs PURPOSE There is a paucity of population -based data on the epidemiology of uveitis in the elderly . In the past 40 years , only 2 U.S. population -based studies have examined the epidemiology of uveitis . The conclusions of these studies on the burden of uveitis in the elderly differ greatly . In this analysis , we use Medicare cl aims data to define the population -based incidence and prevalence of uveitis in the United States elderly population . DESIGN Cohort study . PARTICIPANTS A cohort of 21644 Medicare beneficiaries drawn for the National Long-term Care Survey , a r and om sample of U.S. adults 65 years and older , was followed up from 1991 through 1999 . METHODS The International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes specific to uveitis were queried . To decrease the inclusion of uveitis caused by surgery , diagnoses occurring within 3 months of intraocular surgery were excluded . The incidence and prevalence of uveitis by anatomic location was calculated for each year in the study . MAIN OUTCOME MEASURES The onset of uveitis during a given year and its presence in subsequent years . RESULTS The cumulative yearly incidence of uveitis ranged from 302/100000 to 424/100000 persons per year and averaged 340.9/100000 persons per year . Anterior uveitis was the most common form of uveitis in this population , with a mean incidence of 243.6 cases per 100000 persons per year . The incidence of posterior uveitis averaged 76.6/100000 and the incidence of panuveitis/endophthalmitis averaged 41.7/100000 . Only 2 cases of intermediate uveitis occurred during the study period . The cumulative prevalence of uveitis doubled from 511/100000 in 1991 to 1231/100000 in 1999 , with anterior uveitis accounting for most prevalent cases in every year . CONCLUSIONS The burden of uveitis in the elderly is substantial and is higher than previously thought . Longitudinal analysis of Medicare cl aims data may provide a useful tool for monitoring uncommon diseases , such as uveitis , in the elderly population One hundred twelve unilateral cataract extraction patients were r and omly assigned to receive either a one-piece Staar Model AA-4203 silicone intraocular lens ( IOL ) implanted through a 3.2-millimeter incision , or a one-piece polymethylmethacrylate IOL implanted through a 6.0-millimeter incision . Follow up was 96 % at 1 day postoperatively , 90 % at 3 months , and 70 % at 1 year . Fifty-three percent of the eyes that received a smaller incision could see 20/40 or better uncorrected at 1 day , as compared with 19 % of the eyes that received a 6-millimeter incision ( P < .01 ) . At 3 months , significantly more smaller-incision eyes could still see 20/40 or better ( P = .03 ) . The smaller-incision eyes also had significantly less surgically-induced astigmatism at both 1 day ( P < .01 ) and 3 months ( P = .02 ) , and had significantly less flare ( P < .01 ) and cellular reaction ( P = .04 ) at 1 day 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 compare the efficacy of heparin‐surface‐modified ( HSM ) , poly(methyl methacrylate ) ( PMMA ) posterior chamber intraocular lenses ( IOLs ) with that of unmodified PMMA IOLs in reducing postoperative complications caused by inflammatory reactions after extracapsular cataract extraction in an Asian population . Setting : Departments of Ophthalmology , University of Malaya , Kuala Lumpur , Malaysia , and Tan Tock Seng Hospital , Singapore . Methods : In a r and omized , double‐blind study performed at two centers , 51 patients received an HSM PMMA lens and 48 , an unmodified PMMA IOL . Cell and pigment deposits were evaluated by slitlamp at 1 to 6 days , 2 to 3 weeks , and 3 to 6 months postoperatively . Results : Significantly more eyes with unmodified IOLs had inflammatory cell deposits than those with HSM IOLs at 3 to 6 months ( P < .001 ) and 12 to 14 months ( P = .018 ) postoperatively . The HSM group also had significantly fewer cell deposits per patient at these two follow‐ups . Significantly more eyes in the non‐HSM group had pigment deposits 3 to 6 months after surgery ( P = .049 ) . One year postoperatively , about 85 % of patients in both groups had a best corrected visual acuity of 0.5 or better . Conclusion : Heparin surface modification significantly reduced the inflammatory response to PMMA IOLs in an Asian population for at least 12 to 14 months PURPOSE The authors studied the safety of intraocular lens ( IOL ) implantation in patients with uveitis . METHODS The authors prospect ively r and omized 26 patients with chronic iridocyclitis ( 22 patients ) or pars planitis ( 4 patients ) to undergo IOL implantation or no IOL implantation at the time of cataract surgery . RESULTS There was no statistical difference in visual acuity results at 1 year between the two groups . There was a trend toward better visual acuity in patients with chronic iridocyclitis without IOLs . Cocoon-like dense fibrous membranes enveloped the IOL in two patients . CONCLUSION The authors conclude that IOLs are relatively safe in patients with chronic iridocyclitis but that only a much larger study could determine if the trend toward better visual acuity without an IOL was real Purpose : To evaluate the influence of heparin‐surface‐modified ( HSM ) versus unmodified poly(methyl methacrylate ) ( PMMA ) intraocular lenses ( IOLs ) on the blood‐aqueous barrier ( BAB ) in at‐risk eyes . Setting : Department of Ophthalmology , Bundesknappschaft ’s Hospital , Sulzbach , Germany . Methods : This study comprised 100 patients with predisposing risk factors for BAB destabilization ( e.g. , diabetes mellitus with or without retinopathy , glaucoma , pseudoexfoliation , uveitis ) . One eye in each patient received an HSM IOL and the fellow eye , a conventional unmodified PMMA IOL after phacoemulsification by the same surgeon . Anterior chamber flare was measured with the Kowa 500 laser flare meter 1 day before and 1 day , 1 and 6 weeks , and 3 months after surgery . Results : For most risk factors , mean flare was lower in the HSM group than in the PMMA group at most follow‐ups . Significantly lower flare values ( difference between postoperative and preoperative mean values ) were seen in eyes with the HSM IOL at 6 weeks ( P < .004 ) and 3 months ( P < .003 ; Student ’s t‐test ) . In the group with preoperative elevated flare values , the eyes with the HSM IOL had significantly better results 6 weeks ( P < .0006 ) and 3 months ( P < .01 ) postoperatively . The values in the HSM IOL eyes were also significantly higher in the diabetic with retinopathy group at 3 months ( P < .003 ) . Conclusion : The results confirm the efficacy of IOL surface modification in reducing postoperative intraocular reaction in at‐risk eyes The use of intraocular lenses ( IOLs ) in infancy is controversial because of the rapid growth of the eye during this time and the lack of r and omized control studies and other evidence -based clinical data regarding longterm visual outcomes . Implanting IOLs in infants has important implication s for the development of vision in children . Conventional management of infantile cataracts involves cataract removal with subsequent optical treatment using contact lenses or spectacles , and cataract surgery with primary intraocular lens implantation has several advantages and disadvantages . Most importantly , statistically and clinical ly important differences in outcome between conventional visual rehabilitation after and primary intraocular implantation will determine the ultimate choice of management . There are as yet no large-series , long-term studies in current literature . However , with the availability of appropriate intraocular lenses , increasing technical expertise , and surgical experience , some of these exciting and controversial issues can now be addressed with preliminary data . IOLs provide the best optical correction of aphakia , and primary implantation in infancy is still in its initial phase . The life expectancy of infants is longer and hence long-term safety is an important consideration . Newer and much improved IOL design s and material have been introduced , improving safety . A pilot study of AAPOS members showed that IOL implantation in the under 2 age group is becoming a more common pediatric ophthalmologic procedure , and 61 % of the members surveyed were willing to participate in a r and omized clinical trial to test IOL implantation in infancy . Even 71 % of parents surveyed were willing to allow their infants to take part in a r and omized control trial to address the question of benefits and OBJECTIVE This study aim ed to determine whether heparin surface-modified ( HSM ) intraocular lenses ( IOLs ) with a hydrophilic surface would reduce cell adherence and other postoperative changes compared with the conventional polymethylmethacrylate ( PMMA ) IOLs in patients with either diabetes mellitus or inactive uveitis . DESIGN The study design was a r and omized , double-masked , clinical trial . PARTICIPANTS Twenty-five patients with bilateral cataracts , 14 with inactive anterior uveitis and 11 with diabetes , with an age range of 11 to 81 years ( mean , 52.8 years ) participated . INTERVENTION Bilateral cataract extraction with posterior chamber IOL implantation was measured , each patient receiving an HSM lens in one eye and a PMMA lens in the other . Pharmacia one-piece HSM and PMMA IOLs were used . Postoperative ocular changes were evaluated at regular intervals for 24 months in patients with inactive uveitis and for 6 months in patients with diabetes . Patients and physicians alike were unaware of which eye contained which lens until postoperative results were compiled . Records were kept by a study coordinator . MAIN OUTCOME MEASURES Comparisons of posterior synechiae , IOL cellular deposits , and posterior capsular fibrosis between PMMA and HSM IOLs were measured . RESULTS Using the chi-square test , no statistically significant difference was found between the HSM and PMMA IOLs in the number of cellular deposits found on the anterior IOL surface , the number of adhesions between the iris and IOL , or the incidence of capsular opacification . CONCLUSION The HSM and PMMA IOLs showed similar postoperative results in patients with inactive uveitis or diabetes mellitus PURPOSE To determine the effectiveness and safety of the Softec HD IOL ; and to present refractive outcomes for lenses manufactured at an IOL power tolerance of 0.11 D. METHODS Three-hundred and ninety adult patients requiring removal of a cataractous lens with implantation of a monofocal IOL in at least one eye were eligible for study participation across eight US investigative sites . Patients were enrolled unilaterally . After routine surgery , subjects were examined for adverse events ( AEs ) , best corrected visual acuity ( BCVA ) and manifest refraction correction at 12 months postoperatively . RESULTS Three-hundred and sixty-six ( 95 % ) of patients completed the 12-month postoperative visit . The percent of patients achieving best corrected Snellen acuity 20/40 or better was 98.9 % , and 81.1 % of patients achieved best corrected Snellen acuity 20/25 or better . Of those patients ( 80 % ) implanted with a lens available in 0.25 D increments ( manufactured at a tolerance of 0.11 D ) 40.9 % , 69.8 % and 93.8 % of patients were within ±0.25 D , ±0.50 D and ±1.0 D of predicted target refraction respectively . Overall incidence of cumulative and persistent IOL Grid AEs was 2.2 % with no AE meeting or exceeding the FDA Grid of Historical Controls . CONCLUSIONS The Softec HD IOL is a safe and effective lens . The high manufacturing tolerance of the lens appears to enhance refractive outcomes Purpose : To evaluate the uveal and capsular biocompatibility of hydrophilic acrylic ( Hydroview ® ) and hydrophobic acrylic ( AcrySof ® ) intraocular lenses ( IOLs ) after phacoemulsification in eyes with pseudoexfoliation syndrome ( PEX ) or uveitis and compare the results with those in a control group . Setting : Department of Ophthalmology , University of Vienna , Vienna , Austria . Methods : This prospect i ve nonr and omized comparative trial comprised 143 eyes recruited consecutively . Of these , 49 eyes had PEX , 43 had uveitis , and 51 served as controls . A st and ardized surgical protocol was used . Cell reaction , anterior ( ACO ) and posterior ( PCO ) capsule opacification , and flare were evaluated 1 year after cataract surgery . Results : Regarding uveal biocompatibility , the number of foreign‐body giant cells ( FBGCs ) increased in proportion to associated ocular pathologies in both IOL groups . The difference between the Hydroview control and Hydroview uveitis groups was statistically significant . The number of FBGCs was greater on AcrySof IOLs than on Hydroview IOLs in all 3 groups . The difference in FBGCs between the 2 IOL types was statistically significant in the control and PEX groups . Regarding capsular biocompatibility , lens epithelial cell ( LEC ) outgrowth was inversely correlated with intraocular inflammation . Outgrowth was statistically significantly higher with Hydroview IOLs , occurring in 85 % in the control group , 45 % in the PEX group , and 28 % in the uveitis group ( P < .0001 ) . With AcrySof lenses , the percentages were 0 % , 8 % , and 4 % , respectively . The PEX and uveitis groups were more likely to develop ACO than the control group ( P < .012 ) . There was no statistically significant difference in ACO between the 2 IOL types in the 3 patient groups . The PCO was statistically significantly greater in the uveitis group than in the control group ( P < .026 ) and statistically significantly more dense on Hydroview than on AcrySof IOLs in all 3 patient groups ( P < .002 ) . Flare was statistically significantly higher in the uveitis group than in the PEX and control groups with both IOL types ( P < .012 ) . There was no statistically significant difference in flare between the 2 IOL types . Conclusions : Uveal and capsular biocompatibility depends on the intensity of ocular inflammation . The greater the inflammation , the less the biocompatibility of hydrophilic and hydrophobic acrylic material s. AcrySof stimulated more FBGCs . The Hydroview material had better uveal but poorer capsular biocompatibility than AcrySof . The sharp optic edge effect of the AcrySof IOL and the advantages of the Hydroview lens in normal eyes are less apparent in compromised eyes |
11,291 | 29,931,038 | Conclusions In conclusion , this review suggests that higher intakes of fruit and vegetables lead to both a reduction in proinflammatory mediators and an enhanced immune cell profile | BACKGROUND Inflammation is associated with an increased risk of a range of chronic diseases .
A diet high in fruit and vegetables may help to reduce inflammation , as fruit and vegetables are rich sources of antioxidants and other biologically active substances , which may improve immune function .
OBJECTIVE To summarize the evidence , we executed a systematic review and meta- analysis examining the effects of fruit and /or vegetable intake on inflammatory biomarkers and immune cells in humans with different diseases and conditions . | Wolfberry ( fruit of Lycium barbarum ) has been prized for many years in China for its immunomodulatory property and its high specific antioxidant content . However , clear clinical evidence demonstrating the effect of wolfberry dietary supplementation is still lacking . After our earlier report showing that a proprietary milk-based wolfberry formulation ( Lacto-Wolfberry ) enhances in vivo antigen-specific adaptive immune responses in aged mice , the present study aim ed at demonstrating the effect of dietary Lacto-Wolfberry supplementation on immune functions in the elderly , especially vaccine response known to decline with aging . A 3-month r and omized , double-blinded , placebo-controlled study was conducted on 150 healthy community-dwelling Chinese elderly ( 65 - 70 years old ) supplemented with Lacto-Wolfberry or placebo ( 13.7 grams/day ) . Immune response to influenza vaccine was assessed in the study , along with inflammatory and physical status . No serious adverse reactions were reported during the trial , neither symptoms of influenza-like infection . No changes in body weight and blood pressure , blood chemistry or cells composition , as well as autoantibodies levels were observed . The subjects receiving Lacto-Wolfberry had significantly higher postvaccination serum influenza-specific immunoglobulin G levels and seroconversion rate , between days 30 and 90 , compared with the placebo group . The postvaccination positive rate was greater in the Lacto-Wolfberry group compared to the placebo group , but did not reach statistical significance . Lacto-Wolfberry supplementation had no significant effect on delayed-type hypersensitivity response and inflammatory markers . In conclusion , long-term dietary supplementation with Lacto-Wolfberry in elderly subjects enhances their capacity to respond to antigenic challenge without overaffecting their immune system , supporting a contribution to reinforcing immune defense in this population Abstract This study evaluated the effects of 10-day broccoli ( 250 g/day ) intake on dietary markers and markers of inflammations in young male smokers . A dietary intervention study with a repeated measures crossover design was conducted . Circulating levels of carotenoids , folate , C-reactive protein ( CRP ) , tumor necrosis factor alpha ( TNF-α ) , interleukin 6 ( IL-6 ) , interleukin 6 receptor ( IL-6sR ) and adiponectin were measured . Broccoli intake significantly increased plasma levels of folate ( + 17 % ) and lutein ( + 39 % ) , while no significant effect was observed for TNF-α , IL-6 , IL-6sR or adiponectin . Plasma CRP decreased by 48 % ( post-hoc analysis , p < 0.05 ) following broccoli diet ; this result ed to be independent from the plasma variations in lutein and folate . An inverse correlation between lycopene , TNF-α and IL-6sR was observed at baseline . In conclusion , broccoli consumption may reduce CRP levels in smokers , consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations Obesity and sedentary lifestyle are associated with increased oxidative stress , inflammation and vessel dysfunction . Previous research has shown that an encapsulated fruit/berry/vegetable juice powder ( FBV ) supplement or controlled exercise training improve the markers of redox biology , low- grade inflammation and circulation . The aim of the present study was to assess the effects of 8 weeks of supplementation with FBV or placebo , and a single bout of controlled walking on the markers of oxidation , inflammation and skin capillary microcirculation in forty-two obese pre-menopausal women ( 41 ( sd 5 ) years , non-smokers and BMI 34·5 ( sd 3·8 ) kg/m2 ) using a r and omised , double-blind , placebo-controlled design . All assessment s were made before and after 8 weeks of capsule supplementation , and pre- and post-30 min of controlled treadmill walking at 70 % of VO2max . Venous blood was collected for the determination of carbonyl proteins ( CP ) , oxidised LDL ( ox-LDL ) , total oxidation status ( TOS ) of lipids , malondialdehyde , TNF-α and IL-6 . Capillary blood flow , O2 saturation of Hb ( SO2Hb ) and the relative concentration of Hb ( rHb ) were assessed at a 2 mm skin depth . Following 8 weeks of supplementation , compared with placebo , the FBV group had a significant ( P < 0·05 ) reduction in CP , ox-LDL , TOS and TNF-α , and a significant increase in blood flow , SO2Hb and rHb . Independent of supplementation , moderate exercise significantly increased blood flow and rHb , with a trend towards increased SO2Hb . Compared with placebo , 8 weeks of supplementation with FBV decreased the markers of systemic oxidation and inflammation . Both FBV supplementation and a single walking bout improved the markers of the microcirculation in these obese women In the elderly , immunosenescence and malnourishment can contribute to increased risk and severity of upper respiratory tract infections ( URTI ) . Gold kiwifruit ( Actinidia chinensis ' Hort16A ' ) contains nutrients important for immune function and mitigation of symptoms of infection , including vitamins C and E , folate , polyphenols and carotenoids . The objective of the present study was to evaluate whether regular consumption of gold kiwifruit reduces symptoms of URTI in older people , and determine the effect it has on plasma antioxidants , and markers of oxidative stress , inflammation and immune function . A total of thirty-two community-dwelling people ( ≥65 years ) participated in a r and omised crossover study , consuming the equivalent of four kiwifruit or two bananas daily for 4 weeks , with treatments separated by a 4-week washout period . Participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily , and blood sample s were collected at baseline and at the end of each treatment and washout period . Gold kiwifruit did not significantly reduce the overall incidence of URTI compared with banana , but significantly reduced the severity and duration of head congestion , and the duration of sore throat . Gold kiwifruit significantly increased plasma vitamin C , α-tocopherol and lutein/zeaxanthin concentrations , and erythrocyte folate concentrations , and significantly reduced plasma lipid peroxidation . No changes to innate immune function ( natural killer cell activity , phagocytosis ) or inflammation markers ( high-sensitivity C-reactive protein , homocysteine ) were detected . Consumption of gold kiwifruit enhanced the concentrations of several dietary plasma analytes , which may contribute to reduced duration and severity of selected URTI symptoms , offering a novel tool for reducing the burden of URTI in older individuals Introduction Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children . Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants . Methods A total of 158 asthmatic children recruited at the Children 's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks . Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks . Dietary intake was evaluated using a 108-item food frequency question naire and a fruit and vegetable index ( FVI ) and a Mediterranean diet index ( MDI ) were constructed . The impact of these indices on lung function and interleukin-8 ( IL-8 ) and their interaction with air pollutants were determined using mixed regression models with r and om intercept and r and om slope . Results FVI was inversely related to IL-8 levels in nasal lavage ( p < 0.02 ) with a significant inverse trend ( test for trend p < 0.001 ) , MDI was positively related to lung function ( p < 0.05 ) , and children in the highest category of MDI had a higher FEV1 ( test for trend p < 0.12 ) and FVC ( test for trend p < 0.06 ) than children in the lowest category . A significant interaction was observed between FVI and ozone for FEV1 and FVC as was with MDI and ozone for FVC . No effect of diet was observed among healthy children . Conclusion Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City Phytochemicals from fruit and vegetables reduce systemic inflammation . This study examined the effects of an encapsulated fruit and vegetable ( F&V ) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults . A double-blinded , parallel , r and omized placebo-controlled trial was conducted in 56 adults aged ≥40 years with a body mass index ( BMI ) ≥28 kg/m2 . Before and after eight weeks daily treatment with six capsules of F&V juice concentrate or placebo , peripheral blood gene expression ( microarray , quantitative polymerase chain reaction ( qPCR ) ) , plasma tumour necrosis factor (TNF)α ( enzyme-linked immunosorbent assay ( ELISA ) ) , body composition ( Dual-energy X-ray absorptiometry ( DEXA ) ) and lipid profiles were assessed . Following consumption of juice concentrate , total cholesterol , low-density lipoprotein ( LDL ) cholesterol and plasma TNFα decreased and total lean mass increased , while there was no change in the placebo group . In subjects with high systemic inflammation at baseline ( serum C-reactive protein ( CRP ) ≥3.0 mg/mL ) who were supplemented with the F&V juice concentrate ( n = 16 ) , these effects were greater , with decreased total cholesterol , LDL cholesterol and plasma TNFα and increased total lean mass ; plasma CRP was unchanged by the F&V juice concentrate following both analyses . The expression of several genes involved in lipogenesis , the nuclear factor-κB ( NF-κB ) and 5′ adenosine monophosphate-activated protein kinase ( AMPK ) signalling pathways was altered , including phosphomevalonate kinase ( PMVK ) , zinc finger AN1-type containing 5 ( ZF AND 5 ) and calcium binding protein 39 ( CAB39 ) , respectively . Therefore , F&V juice concentrate improves the metabolic profile , by reducing systemic inflammation and blood lipid profiles and , thus , may be useful in reducing the risk of obesity-induced chronic disease A freeze-dried fruit and vegetable juice powder ( JUICE ) was investigated as a countermeasure nutritional strategy to exercise-induced inflammation , oxidative stress , and immune perturbations in trained cyclists . Thirty-four cyclists ( 25 male , 9 female ) were r and omized to control ( nonJUICE ) or JUICE for 17 days . JUICE provided 230 mg·day(-1 ) of flavonoids , doubling the typical adult daily intake . During a 3-d period of intensified exercise ( days 15 - 17 ) , subjects cycled at 70%-75 % V̇O2max for 2.25 h per day , followed by a 15-min time trial . Blood sample s were collected presupplementation , post supplementation ( pre-exercise ) , and immediately and 14-h post exercise on the third day of exercise . Sample s were analyzed for inflammation ( interleukin (IL)-6 , IL-8 ; tumor necrosis factor alpha ( TNFα ) ; monocyte chemoattractant protein-1 ( MCP-1 ) ) , oxidative stress ( oxygen radical absorbance capacity ( ORAC ) , ferric reducing ability of plasma ( FRAP ) , reduced and oxidized glutathione , protein carbonyls ) , and innate immune function ( granulocyte ( G-PHAG ) and monocyte ( M-PHAG ) phagocytosis and oxidative burst activity ) . A 2 ( group ) × 4 ( time points ) repeated measures ANOVA revealed significant time effects due to 3 days of exercise for IL-6 ( 396 % increase ) , IL-8 ( 78 % increase ) , TNFα ( 12 % increase ) , MCP-1 ( 30 % increase ) , G-PHAG ( 38 % increase ) , M-PHAG ( 36 % increase ) , FRAP ( 12.6 % increase ) , ORAC ( 11 % decrease at 14 h post exercise ) , and protein carbonyls ( 82 % increase at 14 h post exercise ) ( p < 0.01 ) . No significant interaction effects were found for any of the physiological measures . Although providing 695 gallic acid equivalents of polyphenols per day , JUICE treatment for 17 days did not change exercise-induced alterations in inflammation and oxidative stress or immune function in trained cyclists after a 3-day period of overreaching Inflammation and endothelial activation are associated with an increased risk of CVD and epidemiological evidence suggests an association between levels of markers of inflammation or endothelial activation and the intake of fruit . Also , vitamin E , a fat-soluble antioxidant , has anti-inflammatory properties . We performed a r and omised 2 x 2 factorial , crossover trial to determine the effect of orange and blackcurrant juice ( 500 ml/d ) and vitamin E ( 15 mg RRR-alpha-tocopherol/d ) supplementation on markers of inflammation and endothelial activation in forty-eight patients with peripheral arterial disease . Patients were r and omly allocated to two dietary supplements from the four possible combinations of juice and vitamin E : juice+vitamin E ; juice+placebo ; reference beverage ( sugar drink)+vitamin E ; and reference beverage+placebo . The supplementations were given for 28 d , separated by a 4-week wash-out period . Analysis of main effects showed that juice decreased C-reactive protein ( CRP ) by 11 % and fibrinogen by 3 % while the reference drink increased CRP by 13 % and fibrinogen by 2 % ( P<0.008 and P<0.002 , respectively ) . No significant differences were measured for IL-6 and the endothelial activation markers von Willebr and factor , tissue-plasminogen activator and plasmin activator inhibitor-1 . Vitamin E supplementation had no significant effects on the various markers . We observed no significant interaction between juice and vitamin E. In this study , orange and blackcurrant juice reduced markers of inflammation , but not markers of endothelial activation , in patients with peripheral arterial disease , relative to sugar drinks The daily consumption of fruits and vegetables is a common dietary recommendation to support good health . We hypothesized that a commercially available encapsulated fruit and vegetable juice powder concentrate ( FVJC ) could support functional indices of health due to increased intake of various phytonutrients . This was a double-blind , r and omized , placebo-controlled investigation of 59 healthy law students who consumed either FVJC or placebo capsules for 77 d. Blood was collected on d 1 , 35 , and 77 to examine the number of circulating alphabeta- and gammadelta-T cells , cytokine production , lymphocyte DNA damage , antioxidant status , and levels of carotenoids and vitamin C. A log of illnesses and symptoms was also kept . The FVJC group tended to have fewer total symptoms than the placebo group ( P < 0.076 ) . By d 77 there was a 30 % increase in circulating gammadelta-T cells and a 40 % reduction in DNA damage in lymphocytes in the FVJC group relative to the placebo group . Plasma levels of vitamin C and of beta-carotene , lycopene , and lutein increased significantly from baseline in the FVJC group as did plasma oxygen radical absorptive capacity ( 50 % ) . Interferon-gamma produced by phorbol-stimulated lymphocytes was reduced 70 % in the FVJC group , whereas other cytokines ( IL-4 , IL-6 , transforming growth factor beta ) were unchanged relative to treatment or time . FVJC consumption during this study period result ed in increased plasma nutrients and antioxidant capacity , reduction in DNA str and breaks , and an increase in circulating gammadelta-T cells The immunomodulatory potential of carotenoids has been investigated thoroughly only for beta-carotene . Data on the immunomodulatory activity of other carotenoids such as lycopene are scarce . The objective of this study was to investigate the effects of prolonged tomato juice consumption on cell-mediated immunity of well-nourished healthy elderly persons . In an intervention study , 33 female and 20 male subjects ( aged 63 - 86 y ) consumed 330 mL/d tomato juice ( 47.1 mg/d lycopene ) or mineral water for 8 wk . Immune status was assessed by measuring number and lytic activity of natural killer ( NK ) cells , secretion of cytokines [ interleukin (IL)-2 , IL-4 , tumor necrosis factor-alpha ( TNF-alpha ) ] by activated peripheral blood mononuclear cells ( P BMC ) , lymphocyte proliferation , and delayed-type hypersensitivity ( DTH ) skin responses . Tomato juice consumption result ed in significantly increased plasma lycopene and beta-carotene concentrations over time . In both treatment groups , TNF-alpha and IL-4 secretion were increased at the end of the intervention period , whereas IL-2 secretion was decreased . Tomato juice consumption had no effect on lymphocyte proliferation , DTH or the number of NK cells . Lytic activity of NK cells was increased in both groups at the end of the intervention period . In conclusion , these results show that prolonged tomato juice consumption increased plasma lycopene concentrations without significantly affecting cell-mediated immunity in well-nourished elderly subjects BACKGROUND Patients treated with hemodialysis frequently experience cardiovascular complications attributed , among other causes , to dyslipidemia , increased oxidative stress , and inflammation . OBJECTIVE The aim of the study was to study the effects of dietary supplementation with concentrated red grape juice ( RGJ ) , a source of polyphenols , on lipoprotein profile , antioxidant capacity , LDL oxidation , and inflammatory biomarkers . DESIGN Twenty-six patients receiving hemodialysis and 15 healthy subjects were instructed to drink 100 mL RGJ/d for 14 d. Blood was drawn at baseline , twice during RGJ supplementation , and twice during the 6-mo follow-up period . As a control , 12 other r and omly recruited hemodialysis patients not receiving RGJ were studied . Lipids , apolipoproteins , oxidized LDL , and antioxidant vitamins were measured in plasma . The bioavailability of RGJ polyphenols was assessed in healthy subjects . RESULTS The maximum plasma concentration of quercetin was achieved 3 h after RGJ ingestion , which indicates that supplement-derived polyphenols are rapidly absorbed . In both healthy subjects and hemodialysis patients , RGJ consumption increased the antioxidant capacity of plasma without affecting concentrations of uric acid or ascorbic acid ; reduced the concentration of oxidized LDL ; and increased the concentration of cholesterol-st and ardized alpha-tocopherol . RGJ supplementation also caused a significant decrease in LDL-cholesterol and apolipoprotein B-100 concentrations , while increasing the concentrations of HDL cholesterol and apolipoprotein A-I. In a further study in hemodialysis patients , RGJ supplementation for 3 wk significantly reduced plasma monocyte chemoattractant protein 1 , an inflammatory biomarker associated with cardiovascular disease risk . CONCLUSION Dietary supplementation with concentrated RGJ improves the lipoprotein profile , reduces plasma concentrations of inflammatory biomarkers and oxidized LDL , and may favor a reduction in cardiovascular disease risk BACKGROUND Whether different intakes of vegetables and fruit modulate immunologic markers is currently not known . OBJECTIVE We investigated the effects of low , medium , and high intakes of vegetables and fruit on markers of immune functions , including nonspecific markers of inflammation . DESIGN In a r and omized controlled trial , nonsmoking men consumed a diet that included < or = 2 servings/d of vegetables and fruit for 4 wk . The subjects were then r and omly assigned to 1 of 3 groups to consume 2 servings/d , 5 servings/d , or 8 servings/d of carotenoid-rich vegetables and fruit for another 4-wk period . Plasma concentrations of vitamins C and E and carotenoids were measured . The assessment of immunologic and inflammatory markers included the number and activity of natural killer cells , secretion of cytokines , lymphocyte proliferation , and plasma C-reactive protein concentrations . RESULTS The high intake ( 8 servings/d ) of vegetables and fruit significantly increased total carotenoid concentrations in plasma compared with the low intake ( 2 servings/d ; week 4 compared with week 8) , whereas concentrations of vitamins C and E did not differ between week 4 and week 8 . Immunologic markers were not significantly modulated . In contrast , C-reactive protein was significantly reduced at week 8 in the subjects who consumed 8 servings/d of vegetables and fruit compared with those who consumed 2 servings/d . CONCLUSIONS In healthy , well-nourished , nonsmoking men , 4 wk of low or high intakes of carotenoid-rich vegetables and fruit did not affect markers of immune function . However , a high intake of vegetables and fruit may reduce inflammatory processes , as indicated by the reduction of plasma C-reactive protein Increased systemic inflammation and oxidative stress are well established as nontraditional key players in the pathogenesis of atherosclerosis and are also involved in the innate immunity dysregulation in hemodialysis ( HD ) patients . The study aim was to investigate the effect of 1-year intake of pomegranate juice , an antioxidant source , on oxidative stress , inflammation , and long-term clinical outcomes . A r and omized placebo controlled double-blind trial was design ed , enrolling 101 chronic HD patients to receive during each dialysis 100 cc of pomegranate juice , or matching placebo , three times a week for 1 year . The primary endpoints were levels of oxidative stress and inflammation biomarkers . Secondary endpoints were hospitalization due to infections and the progression of atherosclerotic process based on a composite of variables of the carotid arteries : intima media thickness ( IMT ) , number , and structure of plaques . Pomegranate juice intake yielded a significant time response reduction in polymorphonuclear leukocyte priming , protein oxidation , lipid oxidation , and inflammation biomarkers levels . These beneficial effects were abolished 3 months postintervention . Pomegranate juice intake result ed in a significantly lower incidence rate of the second hospitalization due to infections . Furthermore , 25 % of the patients in the pomegranate juice group had improvement and only 5 % progression in the atherosclerotic process , while more than 50 % of patients in the placebo group showed progression and none showed any improvement . Prolonged pomegranate juice intake improves nontraditional CV risk factors , attenuates the progression of the atherosclerotic process , strengthens the innate immunity , and thus reduces morbidity among HD patients OBJECTIVE We have recently shown that a high-fat high-carbohydrate ( HFHC ) meal induces an increase in plasma concentrations of endotoxin ( lipopolysaccharide [ LPS ] ) and the expression of Toll-like receptor-4 ( TLR-4 ) and suppresser of cytokine signaling-3 ( SOCS3 ) in mononuclear cells ( MNCs ) in addition to oxidative stress and cellular inflammation . Saturated fat and carbohydrates , components of the HFHC meal , known to induce oxidative stress and inflammation , also induce an increase in LPS , TLR-4 , and SOCS3 . RESEARCH DESIGN AND METHODS Fasting normal subjects were given 300-calorie drinks of either glucose , saturated fat as cream , orange juice , or only water to ingest . Blood sample s were obtained at 0 , 1 , 3 , and 5 h for analysis . RESULTS Indexes of inflammation including nuclear factor-κB ( NF-κB ) binding , and the expression of SOCS3 , tumor necrosis factor-α ( TNF-α ) , and interleukin (IL)-1β in MNCs , increased significantly after glucose and cream intake , but TLR-4 expression and plasma LPS concentrations increased only after cream intake . The intake of orange juice or water did not induce any change in any of the indexes measured . CONCLUSIONS Although both glucose and cream induce NF-κB binding and an increase in the expression of SOCS3 , TNF-α , and IL-1β in MNCs , only cream caused an increase in LPS concentration and TLR-4 expression . Equicaloric amounts of orange juice or water did not induce a change in any of these indexes . These changes are relevant to the pathogenesis of atherosclerosis and insulin resistance Blueberries are rich in antioxidants known as anthocyanins , which may exhibit significant health benefits . Strenous exercise is known to acutely generate oxidative stress and an inflammatory state , and serves as an on-dem and model to test antioxidant and anti-inflammatory compounds . The purpose of this study was to examine whether 250 g of blueberries per day for 6 weeks and 375 g given 1 h prior to 2.5 h of running at ∼72 % maximal oxygen consumption counters oxidative stress , inflammation , and immune changes . Twenty-five well-trained subjects were recruited and r and omized into blueberry ( BB ) ( N = 13 ) or control ( CON ) ( N = 12 ) groups . Blood , muscle , and urine sample s were obtained pre-exercise and immediately postexercise , and blood and urine 1 h postexercise . Blood was examined for F₂-isoprostanes for oxidative stress , cortisol , cytokines , homocysteine , leukocytes , T-cell function , natural killer ( NK ) , and lymphocyte cell counts for inflammation and immune system activation , and ferric reducing ability of plasma for antioxidant capacity . Muscle biopsies were examined for glycogen and NFkB expression to evaluate stress and inflammation . Urine was tested for modification of DNA ( 8-OHDG ) and RNA ( 5-OHMU ) as markers of nucleic acid oxidation . A 2 ( treatment ) × 3 ( time ) repeated measures ANOVA was used for statistical analysis . Increases in F₂-isoprostanes and 5-OHMU were significantly less in BB and plasma IL-10 and NK cell counts were significantly greater in BB vs. CON . Changes in all other markers did not differ . This study indicates that daily blueberry consumption for 6 weeks increases NK cell counts , and acute ingestion reduces oxidative stress and increases anti-inflammatory cytokines BACKGROUND Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies . We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes . OBJECTIVE The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet , with or without lycopene supplementation , in asthma . DESIGN Asthmatic adults ( n = 137 ) were r and omly assigned to a high-antioxidant diet ( 5 servings of vegetables and 2 servings of fruit daily ; n = 46 ) or a low-antioxidant diet ( ≤2 servings of vegetables and 1 serving of fruit daily ; n = 91 ) for 14 d and then commenced a parallel , r and omized , controlled supplementation trial . Subjects who consumed the high-antioxidant diet received placebo . Subjects who consumed the low-antioxidant diet received placebo or tomato extract ( 45 mg lycopene/d ) . The intervention continued until week 14 or until an exacerbation occurred . RESULTS After 14 d , subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet . Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14 . At the end of the trial , time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group , and the low-antioxidant diet group was 2.26 ( 95 % CI : 1.04 , 4.91 ; P = 0.039 ) times as likely to exacerbate . Of the subjects in the low-antioxidant diet group , no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo . CONCLUSIONS Modifying the dietary intake of carotenoids alters clinical asthma outcomes . Improvements were evident only after increased fruit and vegetable intake , which suggests that whole-food interventions are most effective . This trial was registered at http://www.actr.org.au as ACTRN012606000286549 Tomatoes are the richest source of lycopene , a potent antioxidant . Tomato products improve antioxidant defences and reduce the risk of inflammatory diseases , at least partly , due to the presence of lycopene . Lycopene , as an anti-inflammatory agent , prevents the production of inflammatory cytokines . Obesity is a chronic inflammatory condition in which the increased level of body fat leads to an increase in circulating inflammatory mediators . We hypothesised that the consumption of a lycopene-rich food would reduce inflammation in people who are overweight or obese . A total of 106 overweight or obese female students of the Tehran University of Medical Sciences were enrolled and r and omly allocated to an intervention group ( n 53 ) or a control group ( n 53 ) consuming 330 ml/d of tomato juice or water , respectively , for 20 d. At baseline and day 20 , serum concentrations of IL-6 , IL-8 , high-sensitivity C-reactive protein and TNF-α were analysed by ELISA and compared between the groups . Serum concentrations of IL-8 and TNF-α decreased significantly in the intervention group compared with the control group and with baseline . Subgroup analysis indicated that this effect was confined to subjects who were overweight . Among obese subjects , serum IL-6 concentration was decreased in the intervention group compared with the control group , with no differences in IL-8 and TNF-α observed . Tomato juice reduces inflammation in overweight and obese females . Thus , increasing tomato intake may provide a useful approach for reducing the risk of inflammatory diseases such as CVD and diabetes , which are associated with obesity Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease , diabetes , and cancer . A high " inflammatory load " is defined as elevated inflammation markers in blood or other tissues . We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders ( FVB ) or without ( FV ) could impact markers of inflammatory load . Using a double-blind , placebo-controlled approach , 117 subjects were r and omly assigned to receive placebo , FV , or FVB capsules . Blood was drawn at baseline and after 60 d of capsule consumption . We measured inflammatory markers ( high sensitivity C-Reactive Protein , Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and Regulated upon Activation , Normal T cell Expressed and Secreted ) , superoxide dismutase , and micronutrients ( β-carotene , vitamin C , and vitamin E ) . Results showed Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB , relative to placebo . Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties Evidence suggests that berries contain bioactive compounds , which reduce certain cancers and hypertension . Our hypothesis was that daily blueberry ( BB ) consumption would increase natural killer ( NK ) cells and plasma redox capacity and reduce blood pressure , augmentation index ( AIx ) , central pulse wave velocity , and aortic systolic pressures ( ASPs ) . Twenty-five men and postmenopausal women aged 18 to 50 years were recruited and r and omized to BB ( n , 13 ) or placebo groups ( n , 12 ) . Participants were provided with BB ( equivalent to 250 g berries ) or placebo powders each day for 6 weeks . Blood pressure , vascular performance testing , and blood sample s were taken at baseline ( presupplementation ) . Participants returned after 6 weeks and repeated all procedures . Presupplementation to postsupplementation comparisons for the main effects of treatment , time , and treatment-time interaction were made using a 2 ( treatment ) × 2 ( times ) repeated- measures analysis of variance for all vascular measures , redox status , and NK cell counts . Anthropometric measures were compared using t tests . Body mass , composition , and overall blood pressures were not affected in either group . Overall , AIx and ASPs were decreased in BB ( treatment effect , P = .024 and P = .046 , respectively ) . Plasma redox was not affected . Absolute NK cells were increased in BB ( time , P = .001 and interaction , P = .012 ) . Subjects ( n , 9 ) with prehypertensive pressures ( ≥120/80 mm Hg , respectively ) were examined as a subset using t tests and exhibited significant reductions in diastolic pressure ( P = .038 ) from presupplementation to postsupplementation in BB . We conclude that BB ingestion for 6 weeks increases NK cells and reduces AIx , ASP , and diastolic pressures in sedentary males and females Abstract Purpose Dietary flavonoids , including anthocyanins , may positively influence cognition and may be beneficial for the prevention and treatment of dementia . We aim ed to assess whether daily consumption of anthocyanin-rich cherry juice changed cognitive function in older adults with dementia . Blood pressure and anti-inflammatory effects were examined as secondary outcomes . Methods A 12-week r and omised controlled trial assessed cognitive outcomes in older adults ( + 70 year ) with mild-to-moderate dementia ( n = 49 ) after consumption of 200 ml/day of either a cherry juice or a control juice with negligible anthocyanin content . Blood pressure and inflammatory markers ( CRP and IL-6 ) were measured at 6 and 12 weeks . ANCOVA controlling for baseline and RMANOVA assessed change in cognition and blood pressure . Results Improvements in verbal fluency ( p = 0.014 ) , short-term memory ( p = 0.014 ) and long-term memory ( p ≤ 0.001 ) were found in the cherry juice group . A significant reduction in systolic ( p = 0.038 ) blood pressure and a trend for diastolic ( p = 0.160 ) blood pressure reduction was evident in the intervention group . Markers of inflammation ( CRP and IL-6 ) were not altered . Conclusion Inclusion of an anthocyanin-rich beverage may be a practical and feasible way to improve total anthocyanin consumption in older adults with mild-to-moderate dementia , with potential to improve specific cognitive outcomes Increased consumption of tomato products is associated with a decreased risk of cancer . The present study was performed to investigate whether consumption of a tomato oleoresin extract for 2 weeks can affect endogenous levels of DNA single str and breaks in peripheral blood lymphocytes in healthy non-smokers and smokers . We also assessed , the effect of the tomato oleoresin extract on various immunological functions of peripheral blood mononuclear cells . A double-blinded , r and omized , placebo-controlled study design was used . Over a period of 2 weeks 15 non-smokers and 12 smokers were given three tomato oleoresin extract capsules daily ( each containing 4.88 mg lycopene , 0.48 mg phytoene , 0.44 mg phytofluene and 1.181 mg alpha-tocopherol ) . The control group received placebos . The baseline level of endogenous DNA damage for non-smokers was slightly ( 13 % ) and non-significantly ( P = 0.44 ) lower than that of smokers . Placebo supplementation of non-smokers and smokers for 2 weeks did not significantly affect lycopene plasma levels or DNA damage in either group . Intervention with tomato oleoresin extract result ed in significant increases in total plasma lycopene and result ed in decreased levels of DNA str and breaks of approximately 32 ( non-smokers ) and 39 % ( smokers ) . However , this effect was not statistically significant in either group ( P = 0.09 for non-smokers and P = 0.12 for smokers ) . Analysis of the distribution pattern of DNA str and breaks showed a statistically significant ( P < 0.05 ) increase in the number of comets in class 0 ( undamaged ) and a decrease in classes 1 and 2 ( damaged ) after the tomato oleoresin extract intervention in non-smokers . The changes in the smoker group were not statistically significant . Treatment with the tomato extract had no effect on lymphocyte proliferation , NK cell activity , interleukin (IL)-2 production and tumor necrosis factor (TNF)alpha production , but it significantly reduced IL-4 production in smokers ( P = 0.009 ) Background Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases . However , the mechanisms behind this protective effect are not eluci date d. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells . Trial registration number : NCT00520819 http:// clinical trials.gov . Methods In an 8-week dietary intervention study , 102 healthy male smokers were r and omised to either a diet rich in various antioxidant-rich foods , a kiwifruit diet ( three kiwifruits/d added to the regular diet ) or a control group . Blood cell gene expression profiles were obtained from 10 r and omly selected individuals of each group . Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis ( GSEA ) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays . Results Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group . Groups of genes involved in regulation of cellular stress defence , such as DNA repair , apoptosis and hypoxia , were significantly upregulated ( GSEA , FDR q-values < 5 % ) by both diets compared to the control group . Genes with common regulatory motifs for aryl hydrocarbon receptor ( AhR ) and AhR nuclear translocator ( AhR/ARNT ) were upregulated by both interventions ( FDR q-values < 5 % ) . Plasma antioxidant biomarkers ( polyphenols/carotenoids ) increased in both groups . Conclusions The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes Dietary flavonoid intake , especially berry flavonoids , has been associated with reduced risks of cardiovascular disease ( CVD ) in large prospect i ve cohorts . Few clinical studies have examined the effects of dietary berries on CVD risk factors . We examined the hypothesis that freeze-dried strawberries ( FDS ) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids . In a r and omized dose-response controlled trial , 60 volunteers [ 5 men and 55 women ; aged 49 ± 10 y ; BMI : 36 ± 5 kg/m(2 ) ( means ± SDs ) ] were assigned to consume 1 of the following 4 beverages for 12 wk : 1 ) low-dose FDS ( LD-FDS ; 25 g/d ) ; 2 ) low-dose control ( LD-C ) ; 3 ) high-dose FDS ( HD-FDS ; 50 g/d ) ; and 4 ) high-dose control ( HD-C ) . Control beverages were matched for calories and total fiber . Blood draws , anthropometrics , blood pressure , and dietary data were collected at screening ( 0 wk ) and after 12-wk intervention . Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [ 33 ± 6 mg/dL , 28 ± 7 mg/dL , and 301 ± 78 nmol/L , respectively ( means ± SEMs ) ] vs. LD-FDS ( -3 ± 11 mg/dL , -3 ± 9 mg/dL , and -28 ± 124 nmol/L , respectively ) over 12 wk ( 0 - 12 wk ; all P < 0.05 ) . Compared with controls , only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C ( 0.7 ± 12 and 1.4 ± 9 mg/dL , respectively ) over 12 wk ( 0 - 12 wk ; all P < 0.05 ) . Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk ( LD-FDS : 1.3 ± 0.2 μmol/L ; HD-FDS : 1.2 ± 0.1 μmol/L ) vs. controls ( LD-C : 2.1 ± 0.2 μmol/L ; HD-C : 2.3 ± 0.2 μmol/L ) ( P < 0.05 ) . In general , strawberry intervention did not affect any measures of adiposity , blood pressure , glycemia , and serum concentrations of HDL cholesterol and triglycerides , C-reactive protein , and adhesion molecules . Thus , HD-FDS exerted greater effects in lowering serum total and LDL cholesterol and NMR-derived small LDL particles vs. LD-FDS in the 12-wk study . These findings warrant additional investigation in larger trials . This trial was registered at clinical trials.gov as NCT01883401 Background Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity , specifically γδ-T cell proliferation , after daily consumption of a cranberry beverage , and its effect on health outcomes related to cold and influenza symptoms . Methods The study was a r and omized , double-blind , placebo-controlled , parallel intervention . Subjects drank a low calorie cranberry beverage ( 450 ml ) made with a juice-derived , powdered cranberry fraction ( n = 22 ) or a placebo beverage ( n = 23 ) , daily , for 10 wk . P BMC were cultured for six days with autologous serum and PHA-L stimulation . Cold and influenza symptoms were self-reported . Results The proliferation index of γδ-T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption ( p < 0.001 ) . In the cranberry beverage group , the incidence of illness was not reduced , however significantly fewer symptoms of illness were reported ( p = 0.031 ) . Conclusions Consumption of the cranberry beverage modified the ex vivo proliferation of γδ-T cells . As these cells are located in the epithelium and serve as a first line of defense , improving their function may be related to reducing the number of symptoms associated with a cold and flu . Trial registration Clinical Trials.gov Identifier : NCT01398150 Obesity increases the risk of developing bacterial and viral infections compared with normal weight . In a 7-week double-blind , r and omised , cross-over trial , twenty obese volunteers ( BMI between 30 and 40 kg/m² ) were fed freeze-dried strawberry powder or strawberry-flavoured placebo preparations to determine the effects of dietary strawberries on immune function . Blood was collected at six time points during the study and peripheral blood mononuclear cells ( P BMC ) were isolated at each time point and activated with CD3 plus CD28 antibodies ( T-lymphocyte activation ) or lipopolysaccharide ( LPS , monocyte activation ) . Interferon-γ , TNF-α , IL-4 and IL-10 were measured in supernatants from the activated T cells . Supernatants from the activated monocytes were analysed for the production of TNF-α , IL-1β , IL-6 and IL-8 . P BMC were pre-stained with PKH ( Paul Karl Horan ) dye and activated with CD3 plus CD28 antibodies to determine the proliferative responses of CD4⁺ and CD8⁺ T-lymphocytes by flow cytometry . To detect global changes in gene expression , microarray analysis was performed on LPS- and vehicle-treated P BMC from two subjects before and after the strawberry intervention . No difference was observed for the production of T-cell cytokines between the intervention groups . The production of TNF-α was increased in the supernatants from LPS-activated P BMC in the group consuming strawberries compared with the placebo . A modest increase in the proliferation of the CD8⁺ T-lymphocyte population was observed at 24 h post-activation . These data suggest that dietary strawberries may increase the immunological response of T-lymphocytes and monocytes in obese people who are at greater risk for developing infections BACKGROUND AND AIMS Kiwifruit has the potential to improve markers of metabolic dysfunction , but the response may be influenced by inflammatory state . We aim ed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation . METHODS AND RESULTS Eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in , before r and omisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet ( intervention ) or healthy diet alone ( control ) . Anthropometric measures and fasting blood sample s ( plasma lipids , serum apolipoproteins A1 and B , high-sensitivity C-reactive protein ( hs-CRP ) and interleukin (IL)-6 , tumour necrosis factor-alpha ( TNF-α ) and IL-10 ) were taken at baseline , 4 and 8 weeks . Subjects were divided into low and medium inflammatory groups , using pre-intervention hs-CRP concentrations ( hs-CRP < 1 and 1 - 3 mg/L , respectively ) . In the medium inflammatory group the kiwifruit intervention result ed in significant improvements in plasma high-density lipoprotein cholesterol ( HDL-C ) ( mean difference 0.08 [ 95 % CI : 0.03 , 0.12 ] mmol/L [ P < 0.001 ] ) , total cholesterol (TC)/HDL-C ratio ( -0.29 [ -0.45 , -0.14 ] mmol/L [ P = 0.001 ] ) , plasma hs-CRP ( -22.1 [ -33.6 , -4.97]% [ P = 0.01 ] ) and IL-6 ( -43.7 [ -63.0 , -14.1]% [ P = 0.01 ] ) compared to control treatment . No effects were seen in the low inflammatory group . There were significant between inflammation group differences for TC/HDL-C ( P = 0.02 ) , triglyceride (TG)/HDL-C ( P = 0.05 ) , and plasma IL-6 ( P = 0.04 ) . CONCLUSIONS Inflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP , suggesting this group may particularly benefit from the regular consumption of green kiwifruit . Registered 16th March 2010 , Australian New Zeal and Clinical Trials Registry ( no. ACTRN12610000213044 ) , www.ANZCTR.org.au Objective : C-reactive protein ( CRP ) may directly affect the progression of atherosclerosis , and therefore , may be a target for reducing disease risk . The objective was to determine whether antioxidant supplementation reduces plasma CRP in active and passive smokers . Design : R and omized , double-blind , placebo-controlled , parallel group trial with 2 months exposure to study supplements . Setting : Berkeley and Oakl and , California . Subjects : Healthy adult men and women , consuming < 4 daily servings of fruits and vegetables , and who were actively or passively exposed to cigarette smoke . Analysis was limited to participants with detectable baseline CRP concentrations and no evidence of inflammation associated with acute illness at baseline or follow-up as reflected in CRP elevations ( ≥10.0 mg/L ) . A total of 1393 individuals were screened , 216 r and omized , 203 completed the study , and 160 were included in the analysis . Interventions : Participants were r and omized to receive a placebo or vitamin C ( 515 mg/day ) or antioxidant mixture ( per day : 515 mg vitamin C , 371 mg α-tocopherol , 171 mg γ-tocopherol , 252 mg mixed tocotrienols , and 95 mg α-lipoic acid ) . Measures of Outcome : Change in plasma CRP concentration . Results : Vitamin C supplementation yielded a 24.0 % reduction ( 95 % confidence interval , −38.9 % to −5.5 % , p = 0.036 compared to control ) in plasma CRP , whereas the antioxidant mixture and placebo produced a nonsignificant 4.7 % reduction ( −23.9 % to 19.3 % ) and 4.3 % increase ( −15.1 % to 28.2 % ) , respectively . Results were adjusted for baseline body mass index and CRP concentrations . Conclusions : Plasma CRP itself may serve as a potential target for reducing the risk of atherosclerosis , and antioxidants , including vitamin C , should be investigated further to confirm their CRP-lowering and anti-inflammatory effects Serum interleukin-6 ( IL-6 ) , a proinflammatory cytokine , is considered an indicator of inflammation and may be an indicator of colorectal carcinogenesis given that inflammation can promote carcinogenesis . Flavonols , which can be found in fruits and vegetables , may inhibit colorectal carcinogenesis partly by inhibiting inflammation . We estimated odds ratios and 95 % confidence intervals ( 95 % CI ) to determine whether serum IL-6 was associated with colorectal adenoma recurrence and flavonol intake and thus may serve as a risk indicator and as a response indicator to dietary flavonols . Serum IL-6 concentrations at baseline , year 1 , and year 3 were measured in 872 participants from the intervention arm of the Polyp Prevention Trial , a 4-year trial that examined the effectiveness of a low-fat , high-fiber , high-fruit and vegetable diet on adenoma recurrence . Intake of flavonols , especially of isorhamnetin , kaempferol , and quercetin , was inversely associated with serum IL-6 concentrations ( highest versus lowest flavonol intake quartile , 1.80 versus 2.20 pg/mL ) and high-risk ( OR , 0.51 ; 95 % CI , 0.26 - 0.98 ) and advanced adenoma recurrence ( OR , 0.17 ; 95 % CI , 0.06 - 0.50 ) . A decrease in IL-6 concentration during the trial was inversely associated with high-risk ( OR , 0.44 ; 95 % CI , 0.23 - 0.84 ) and advanced adenoma recurrence ( OR , 0.47 ; 95 % CI , 0.19 - 1.18 ) . Individuals with above median flavonol intake and equal or below median IL-6 change after baseline had the lowest risk of recurrence of high-risk and advanced adenoma . Our results suggest that serum IL-6 may serve as a risk indicator and as a response indicator to dietary flavonols for colorectal cancer prevention . Cancer Prev Res ; 3(6 ) ; 764–75 . © 2010 AACR Obese individuals are at an increased risk of developing CVD , hypertension , type 2 diabetes , and bacterial and viral infections when compared with the normal-weight population . In a 9-week r and omised , double-blind , cross-over study , twenty-four obese subjects aged between 20 and 60 years and with a BMI between 30 and 45 kg/m2 were fed grape or placebo powder for 3-week intervals to determine the effects of dietary grapes on blood lipid profiles , plasma inflammatory marker concentrations and immune cell function . Blood sample s were collected on days 1 and 8 for obtaining baseline information and at weeks 3 , 4 , 8 and 9 . Comprehensive chemistry panels , lipid profile analyses by NMR , measurement of plasma inflammatory marker concentrations , and analyses of cytokine production by activated T lymphocytes and monocytes were performed for each blood draw . Dietary grape powder reduced the plasma concentrations of large LDL-cholesterol and large LDL particles compared with the placebo powder ( P < 0·05 ) . The concentrations of interferon-γ , TNF-α , IL-4 and IL-10 were measured in supernatants from peripheral blood mononuclear cells ( P BMC ) activated with anti-CD3/CD28 antibodies and those of TNF-α , IL-1β , IL-6 and IL-8 were measured in supernatants from P BMC activated with lipopolysaccharide ( LPS ) . No difference in the production of T-cell cytokines was observed between the two intervention groups . The production of IL-1β and IL-6 was increased in supernatants from LPS-activated P BMC in the grape powder group compared with the placebo powder group ( P < 0·05 ) . These data suggest that dietary grapes may decrease atherogenic lipid fractions in obese individuals and increase the sensitivity of monocytes in a population at a greater risk of developing infections Epidemiological evidence supports a positive relationship between fruit and vegetable ( FV ) intake , lung function and chronic obstructive pulmonary disease ( COPD ) . Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD . An exploratory r and omised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted . 81 symptomatically stable patients with a habitually low FV intake ( two or fewer portions of FV per day ) were r and omised to the intervention group ( five or more portions of FV per day ) or the control group ( two or fewer portions of FV per day ) . Each participant received self-selected weekly home deliveries of FV for 12 weeks . 75 participants completed the intervention . There was a significant between-group change in self-reported FV intake and biomarkers of FV intake ( zeaxanthin ( p=0.034 ) and & bgr;-cryptoxanthin ( p=0.015 ) ) , indicating good compliance ; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day , respectively . There were no significant changes in biomarkers of airway inflammation ( interleukin-8 and myeloperoxidase ) and systemic inflammation ( C-reactive protein ) or airway and systemic oxidative stress ( 8-isoprostane ) . This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake ; however , this had no significant effect on airway or systemic oxidative stress and inflammation OBJECTIVE To compare the effects of short-term dietary supplementation with tomato juice , vitamin E , and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein ( C-RP ) and cell adhesion molecules in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 57 patients with well-controlled type 2 diabetes aged < 75 years treated with placebo for 4 weeks and then r and omized to receive tomato juice ( 500 ml/day ) , vitamin E ( 800 U/day ) , vitamin C ( 500 mg/day ) , or continued placebo treatment for 4 weeks . Susceptibility of LDL to oxidation ( lag time ) and plasma concentrations of lycopene , vitamin E , vitamin C , C-RP , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 were measured at the beginning of the study , after the placebo phase , and at the end of the study . RESULTS Plasma lycopene levels increased nearly 3-fold ( P = 0.001 ) , and the lag time in isolated LDL oxidation by copper ions increased by 42 % ( P = 0.001 ) in patients during supplementation with tomato juice . The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E ( 54 % ) . Plasma C-RP levels decreased significantly ( -49 % , P = 0.004 ) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study . CONCLUSIONS This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E , which also decreases plasma levels of C-RP , a risk factor for myocardial infa rct ion , in patients with diabetes . These findings may be relevant to strategies aim ed at reducing risk of myocardial infa rct ion in patients with diabetes The present study assessed whether increased fruit and vegetable ( F&V ) intake reduced the concentrations of the inflammatory marker serum amyloid A ( SAA ) in serum , HDL2 and HDL3 and whether the latter reduction influenced any of the functional properties of these HDL subfractions . The present study utilised sample s from two previous studies : ( 1 ) the FAVRIT ( Fruit and Vegetable R and omised Intervention Trial ) study - hypertensive subjects ( systolic blood pressure ( BP ) range 140 - 190 mmHg ; diastolic BP range 90 - 110 mmHg ) were r and omised to receive a 1- , 3- or 6-portion F&V/d intervention for 8 weeks , and ( 2 ) the ADIT ( Ageing and Dietary Intervention Trial ) study - older subjects ( 65 - 85 years ) were r and omised to receive a 2- or 5-portion F&V/d intervention for 16 weeks . HDL2 and HDL3 were isolated by rapid ultracentrifugation . Measurements included the following : serum high-sensitive C-reactive protein ( hsCRP ) by an immunoturbidimetric assay ; serum IL-6 and E-selectin and serum- , HDL2- and HDL3-SAA by ELISA procedures ; serum- , HDL2- and HDL3-cholesterol ester transfer protein ( CETP ) activity by a fluorometric assay . Although the concentrations of hsCRP , IL-6 and E-selectin were unaffected by increasing F&V intake in both studies ( P>0·05 for all comparisons ) , those of SAA in HDL3 decreased in the FAVRIT cohort ( P= 0·049 ) and those in HDL2 and HDL3 decreased in the ADIT cohort ( P= 0·035 and 0·032 ) , which was accompanied by a decrease in the activity of CETP in HDL3 in the FAVRIT cohort ( P= 0·010 ) and in HDL2 in the ADIT cohort ( P= 0·030 ) . These results indicate that SAA responds to increased F&V intake , while other inflammatory markers remain unresponsive , and this leads to changes in HDL2 and HDL3 , which may influence their antiatherogenic potential . Overall , the present study provides tangible evidence of the effectiveness of increased F&V intake , which may be of use to health policy makers and the general public Background : β-Carotene has been shown to enhance immune functions in humans . Whether vegetables rich in carotenoids , such as β-carotene or lycopene , modulate immune functions in healthy humans is presently not known . The objective of this study was to investigate the effects of a low-carotenoid diet supplemented with either tomato ( providing high amounts of lycopene ) or carrot juice ( providing high amounts of α- and β-carotene ) on immune functions in healthy men . Method : In a blinded , r and omized , cross-over study , male subjects on a low-carotenoid diet consumed 330 ml/day of either tomato juice ( 37.0 mg/day lycopene ) or carrot juice ( 27.1 mg/day β-carotene and 13.1 mg/day α-carotene ) for 2 weeks with a 2-week depletion period after juice intervention . Immune status was assessed by measuring lytic activity of natural killer ( NK ) cells , secretion of cytokines ( IL-2 , IL-4 , TNFα ) , and proliferation by activated peripheral blood mononuclear cells . Results : Juice consumption result ed in relatively fast responses in plasma carotenoid concentrations ( p < 0.0002 ) which were not accompanied by concomitant changes in immune functions . For IL-2 , NK cell cytotoxicity , and lymphocyte proliferation , maximum responses were observed during depletion periods . The highest production rate was measured only for TNFα at the end of the first intervention period . Juice intervention did not modulate the secretion of IL-4 . Conclusions : Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet This r and omized , double-blind , parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness ( CIMT ) progression rates in subjects at moderate risk for coronary heart disease . Subjects were men ( 45 to 74 years old ) and women ( 55 to 74 years old ) with > or = 1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm , without significant stenosis . Participants consumed 240 ml/day of pomegranate juice ( n = 146 ) or a control beverage ( n = 143 ) for up to 18 months . No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments . In exploratory analyses , in subjects in the most adverse tertiles for baseline serum lipid peroxides , triglycerides ( TGs ) , high-density lipoprotein ( HDL ) cholesterol , TGs/HDL cholesterol , total cholesterol/HDL cholesterol , and apolipoprotein-B100 , those in the pomegranate juice group had significantly less anterior wall and /or composite CIMT progression versus control subjects . In conclusion , these results suggest that in subjects at moderate coronary heart disease risk , pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis γδ T cells are important immune surveillance cells residing in epithelial layers lining the intestine , lung , and reproductive tract . The main objective of this study was to test the hypothesis that consumption of dietary compounds from grapes would modify γδ T-cell function . Other factors related to immune function after grape juice consumption were also tested . A r and omized , double-blind , placebo-controlled , parallel intervention was conducted : 100 % grape juice made from Concord grapes or a placebo beverage was consumed by 85 individuals daily for 9 weeks . Subjects were asked not to consume other red , blue , and purple fruits during the study . Blood sample s , taken at the beginning and the end , were analyzed for γδ T-cell numbers and proliferation , vitamin C , antioxidant capacity , and the ability to protect DNA from str and breaks . Those consuming the grape juice had significantly greater numbers of circulating γδ T cells and higher serum vitamin C levels compared to the placebo by two-way repeated-measure analysis of variance ( P < .05 ) . Individuals consuming the placebo had lower serum antioxidant activity , less γδ T-cell proliferation , and increased DNA str and breaks when challenged with H(2)O(2 ) . Analysis of the data by structural equation modeling confirmed that 61 % of the variance in biological functions at 9 weeks was due to grape juice consumption . Based on conventional statistical analyses , as well as on sophisticated modeling techniques , regular consumption of purple grape juice in the absence of other red , blue , or purple fruits benefited immunity in healthy , middle-aged human subjects A human intervention study was conducted to determine the effect of the consumption of carotenoid-rich vegetables on the immune system . Subjects , ( twenty-three men ) , who were non-smokers , were not restricted in their daily diet , except that they had to abstain from fruit and vegetables high in carotenoids throughout the whole study period . The study was divided into four periods , each lasting 2 weeks : weeks 1 - 2 : low-carotenoid period ; throughout weeks 3 - 8 : daily consumption of 330 ml tomato juice ( 40 mg lycopene/d , 1.5 mg beta-carotene/d ) ( weeks 3 - 4 ) , 330 ml carrot juice ( 21.6 mg beta-carotene/d , 15.7 mg alpha-carotene/d , 0.5 mg lutein/d ) ( weeks 5 - 6 ) , 10 g dried spinach powder ( 11.3 mg lutein/d , 3.1 mg beta-carotene/d ) ( weeks 7 - 8 ) . Blood was collected weekly from subjects after a 12 h fast . T-lymphocyte functions were assessed by measuring proliferation and secretion of immunoreactive cytokines . The consumption of a low-carotenoid diet result ed in a significantly reduced proliferation of peripheral blood mononuclear cells ( P BMC ) cultured with concanavalin A. After 2 weeks of tomato juice consumption and until the end of the intervention period lymphocyte proliferation was not significantly changed compared with proliferation at the end of the depletion period . Secretion of cytokines by T-helper-1-like lymphocytes ( interleukin (IL)-2 ) and by T-helper-2-like lymphocytes ( IL-4 ) was influenced by the dietary intervention . IL-2 and IL-4 secretion values were significantly suppressed after the low-carotenoid diet ( P < 0.001 and P < 0.05 respectively compared with baseline ) . Tomato juice consumption significantly enhanced IL-2 ( P < 0.001 ) and IL-4 secretion ( P < 0.05 ) compared with the end of depletion period . After carrot juice and spinach powder consumption the cytokine secretion capacity of P BMC was not significantly different from that at the end of the depletion period . In conclusion , the results of the present study indicate that a low-carotenoid diet reduces T-lymphocyte functions and addition of tomato juice restores these functions . This modulation could not be explained by changes in the plasma carotenoid concentrations . The active constituents in tomato juice as well as the biological significance of this immunomodulation remain to be determined Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative , immunomodulatory and antigenotoxic effects . In a r and omized crossover study in healthy men on a low-polyphenol diet , we determined the effects of 2 polyphenol-rich juices ( 330 ml/d ) supplemented for 2 weeks on bioavailability of polyphenols , markers of antioxidative and immune status , and reduction of DNA damage . Juices provided 236 mg ( A ) and 226 mg ( B ) polyphenols with cyanidin glycosides ( A ) and epigallocatechin gallate ( B ) as major polyphenolic ingredients . There was no accumulation of plasma polyphenols after two weeks of juice supplementation . In contrast , plasma malondialdehyde decreased with time during juice interventions . Moreover , juice consumption also increased lymphocyte proliferative responsiveness , with no difference between the two juices . Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices . Juice intervention had no effect on single DNA str and breaks , but significantly reduced oxidative DNA damage in lymphocytes . A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion . We conclude that consumption of either juice enhanced antioxidant status , reduced oxidative DNA damage and stimulated immune cell functions . However , fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting . Further studies should focus on the time-delay between juice intake and changes in measured physiological functions , as well as on active polyphenolic metabolites mediating the observed effects Objective : To study the effect of sea buckthorn berries on the number and duration of common cold ( CC ) infections . As secondary objectives the effects on digestive and urinary tract infections ( DTI , UTI ) , and serum C-reactive protein ( CRP ) concentrations were also investigated . Subjects : A total of 254 healthy volunteers were r and omly assigned to receive sea buckthorn or placebo product during the study , which 233 of them completed . Results : There were no significant differences in the number or duration of CC or DTI between groups ( CC : relative risks ( sea buckthorn vs placebo ) for the number and duration were 1.15 ( 95 % CI 0.90–1.48 ) and 1.05 ( 95 % CI 0.87–1.27 ) , respectively ) . In the sea buckthorn group , as compared to the placebo , the serum CRP concentrations decreased significantly ( difference in median change −0.059 mg/l , P=0.039 ) . The number of UTI was too small to draw solid conclusions , but the results indicate the subject merits further investigation . Conclusion : Sea buckthorn berries did not prevent CC or DTI . However , a reductive effect on CRP , a marker of inflammation , and a risk factor for cardiovascular diseases , was detected Lycium barbarum has been traditionally used in combination with several herbs for medicinal properties , but systematic modern clinical evaluation as a single herb has not been reported . To examine the systematic effects of L. barbarum on immune function , general well-being , and safety , we tested the effects of a st and ardized L. barbarum fruit juice ( GoChi , FreeLife International , Phoenix , AZ , USA ) at 120 mL/day , equivalent to at least 150 g of fresh fruit , the amount traditionally used , or placebo for 30 days in a r and omized , double-blind , placebo-controlled clinical study in 60 older healthy adults ( 55 - 72 years old ) . The GoChi group showed a statistically significant increase in the number of lymphocytes and levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the placebo group , whereas the number of CD4 , CD8 , and natural killer cells or levels of interleukin-4 and immunoglobulin A were not significantly altered . The placebo group showed no significant changes in any immune measures . Whereas the GoChi group showed a significant increase in general feelings of well-being , such as fatigue and sleep , and showed a tendency for increased short-term memory and focus between pre- and post-intervention , the placebo group showed no significant positive changes in these measures . No adverse reactions , abnormal symptoms , or changes in body weight , blood pressure , pulse , visual acuity , urine , stool , or blood biochemistry were seen in either group . In conclusion , daily consumption of GoChi significantly increased several immunological responses and subjective feelings of general well-being without any adverse reactions BACKGROUND Oxidative and inflammatory stresses are involved in the pathogenesis of atherosclerosis . The consumption of fruit and vegetables is associated with improved health and reduced cardiovascular risk . Red oranges have a high content of antioxidant and antiinflammatory substances , but there is a paucity of data concerning their effects on cardiovascular biomarkers in subjects with increased cardiovascular risk . OBJECTIVE We investigated the effect of red orange juice intake on endothelial function , oxidative stress , and markers of inflammation in subjects with increased cardiovascular risk . DESIGN Nineteen nondiabetic subjects with increased cardiovascular risk ( aged 27 - 56 y ) were included in a r and omized , placebo-controlled , single-blind crossover study and compared with 12 healthy , nonobese control subjects . In 2 periods of 7 d each with a 3-d interval , each participant alternatively received 500 mL red orange juice/d and 500 mL placebo/d in a r and om sequence . All measurements were performed in the morning after overnight fasting . RESULTS Endothelial function , which was measured as flow-mediated dilation , significantly improved and was normalized ( 5.7 % compared with 7.9 % ; P < 0.005 ) after 1 wk of red orange juice consumption . Similarly , concentrations of high-sensitivity C-reactive protein , IL-6 , and TNF-α significantly decreased ( P < 0.001 ) . Red orange juice had no significant effect on nitric oxide plasma concentrations . CONCLUSION A 7-d consumption of red orange juice ameliorates endothelial function and reduces inflammation in nondiabetic subjects with increased cardiovascular risk . This trial was registered at biomed central .com as IS RCT N39987296 Background : Diabetes causes the increased concentration of circulatory cytokines as a result of inflammation . Considering that pomegranate juice ( PJ ) is known to have antioxidant and anti-inflammatory properties , the purpose of this study was to determine the effects of PJ consumption on markers of inflammation in patients with type 2 diabetes ( T2D ) . Material s and Methods : In a r and omized , double-blind clinical trial study , 50 patients with T2D ( 40 - 65 years old ) were r and omly assigned to one of two groups . Participants in each group received either 250 mL/day PJ or a control beverage for 12 weeks . Biochemical markers including fasting plasma glucose ( FPG ) , insulin and inflammatory markers were assayed on the baseline and follow-up blood sample s. Results : In all , 44 patients in two groups were included in the analysis : PJ ( n = 22 ) and placebo ( n = 22 ) . After 12 weeks of intervention , in the PJ group , there were 32 % and 30 % significant decreases in plasma C-reactive protein ( hs-CRP ) and Interlukin-6 , respectively ( P < 0.05 ) . The mean ± SD plasma interlukin-6 ( 7.1 ± 5.6 vs. 11.9 ± 14.4 mg/L ) and hs-CRP ( 1791 ± 1657 and 1953 ± 1561 ng/mL ) concentrations in the PJ group were significantly lower than the placebo group after intervention ( P < 0.05 ) . Conclusion : PJ consumption by patients with T2D does not affect FPG or the insulin resistance index ( HOMA-IR ) , whereas it does reduce Interlukin-6 and hs-CRP concentrations in plasma . Therefore , PJ consumption may have an anti-inflammatory effect in patients with T2D Objective : We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive ( HIV+ ) and HIV-seronegative ( HIV− ) subjects . Design : R and omized , prospect i ve pilot intervention study . Setting : University of Bonn , Department of General Internal Medicine . Subjects : A total of 23 HIV+ subjects from the HIV outpatient clinic , 18 HIV− controls . Interventions : Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet . Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline , during 16-weeks of intervention , and after a 6-week washout . Proliferation was assessed by 3H – thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry . Results : Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation ( mitotic index ) in HIV+ patients from 18±16 to 40±34 ( P=0.004 ) and in healthy controls from 27±16 to 51±21 ( P=0.016 ) . Apoptosis was not affected in HIV+ patients , but rose in healthy controls from 9±10 to 34±11 ( apoptotic index ; P=0.001 ) . Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV+ and HIV− subjects . Conclusions : Even though apoptosis did not change in HIV+ subjects , ingestion of polyphenol-rich fruit juices might be favorable to HIV+ patients due to enhanced proliferation , which could restore disturbances in T-cell homeostasis . In healthy controls , increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis . Sponsorship : HG Berner GmbH , Altenholz ; Eckes Granini GmbH & Co. KG , Nieder-Olm ; Graduiertenförderung Nordrhein-Westfalen The search for complementary treatments in primary prevention of cardiovascular disease ( CVD ) is a high-priority challenge . Grape and wine polyphenol resveratrol confers CV benefits , in part by exerting anti-inflammatory effects . However , the evidence in human long-term clinical trials has yet to be established . We aim ed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD . Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded , r and omized , parallel , dose-response , placebo-controlled , 1-year follow-up trial . Patients , allocated in 3 groups , consumed placebo ( maltodextrin ) , a resveratrol-rich grape supplement ( resveratrol 8 mg ) , or a conventional grape supplement lacking resveratrol , for the first 6 months and a double dose for the next 6 months . In contrast to placebo and conventional grape supplement , the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein ( -26 % , p = 0.03 ) , tumor necrosis factor-α ( -19.8 % , p = 0.01 ) , plasminogen activator inhibitor type 1 ( -16.8 % , p = 0.03 ) , and interleukin-6/interleukin-10 ratio ( -24 % , p = 0.04 ) and increased anti-inflammatory interleukin-10 ( 19.8 % , p = 0.00 ) . Adiponectin ( 6.5 % , p = 0.07 ) and soluble intercellular adhesion molecule-1 ( -5.7 % , p = 0.06 ) tended to increase and decrease , respectively . No adverse effects were observed in any patient . In conclusion , 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk ( i.e. , with diabetes or hypercholesterolemia plus ≥1 other CV risk factor ) . Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold st and ard therapy in the primary prevention of CVD OBJECTIVE Oxidative stress and inflammation are involved in the pathogenesis of non-alcoholic fatty liver disease ( NAFLD ) . Bayberries contain high levels of polyphenols that possess antioxidative and anti-inflammatory properties in vitro . The purpose of this study was to investigate whether the consumption of bayberry juice beneficially alters the levels of oxidative , inflammatory , and apoptotic biomarkers in young individuals with features of NAFLD . METHODS In this r and omized , placebo-controlled , double-blind , crossover study , 44 participants ( ages 18 - 25 y ) were given 250 mL of either bayberry juice or placebo twice daily for 4 wk . Several anthropometric characteristics were measured , and fasting blood sample s were drawn before and after each intervention period . The levels of plasma glucose , insulin , lipids , and some NAFLD-related biomarkers were determined . RESULTS No significant effects on the anthropometric parameters and the homeostasis model assessment for insulin resistance were observed . Compared with placebo , the consumption of bayberry juice significantly decreased the plasma levels of protein carbonyl groups ( P = 0.038 ) , tumor necrosis factor-α ( P < 0.001 ) , and interleukin-8 ( P = 0.022 ) . The apoptosis markers analysis revealed significant differences between the treatment and the placebo in the levels of tissue polypeptide-specific antigen ( P < 0.001 ) and cytokeratin-18 fragment M30 ( P < 0.001 ) . CONCLUSION The consumption of bayberry juice for a period of 4 wk can protect against NAFLD in young adults by improving the plasma antioxidant status and inhibiting the inflammatory and apoptotic responses that are involved in this disease Summary . Background : High intake of vegetables and fruits is associated with decreased risk of coronary heart disease . Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits , such as flavonoids . Aim of the study : To study the effects of high and low intake of vegetables , berries and apple on platelet function and inflammatory markers . Methods : The study was a r and omised , controlled parallel human dietary intervention with healthy female and male volunteers ( n = 77 , 19–52 y ) . Nineteen healthy volunteers served as controls . The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables , berries and apple and rich either in linoleic acid ( 11 % of energy , en% ) or oleic acid ( 12 en% ) . Blood and three 24-hour urine sample s were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation . Results : No differences between the treatment groups were seen in platelet count or volume , markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide , protein kinase C activity , urinary 2,3-dinor-thromboxane B2 excretion , plasma P-selectin ) , plasma intercellular adhesion molecule-1 , sensitive C-reactive protein , or antiphospholipid antibodies . Conclusions : The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables , berries and apple do not differ in their effects on platelets or inflammation Anthocyanins ( ACN ) can exert beneficial health effects not only through their antioxidative potential but also through modulation of inflammatory parameters that play a major role in CVD . A r and omised cross-over study was carried out to investigate the effects of ACN-rich beverage ingestion on oxidation- and inflammation-related parameters in thirty healthy female volunteers . The participants consumed 330 ml of beverages ( placebo , juice and smoothie with 8·9 ( SD 0·3 ) , 983·7 ( SD 37 ) and 840·9 ( SD 10 ) mg/l ACN , respectively ) over 14 d. Before and after each intervention , blood and 24 h urine sample s were collected . Plasma superoxide dismutase ( SOD ) and catalase activities increased significantly after ACN-rich beverage ingestion ( P<0·001 ) , whereas after placebo juice ingestion no increase could be observed . Plasma glutathione peroxidase and erythrocyte SOD activities were not affected . An increase in Trolox equivalent antioxidant capacity could also be observed after juice ( P<0·001 ) and smoothie ( P<0·01 ) ingestion . The plasma and urinary concentrations of malondialdehyde decreased after ACN-rich beverage ingestion ( P<0·001 ) , whereas those of 8-OH-2-deoxyguanosine as well as inflammation-related parameters ( IL-2 , -6 , -8 and -10 , C-reactive peptide , soluble cluster of differentiation 40 lig and , TNF-α , monocyte chemoattractant protein-1 and soluble cell adhesion molecules ) were not affected . Thus , ingestion of ACN-rich beverages improves antioxidant enzyme activities and plasma antioxidant capacity , thus protecting the body against oxidative stress , a hallmark of ongoing atherosclerosis Flavanol-rich lychee fruit extract ( FRLFE ) is a processed lychee fruit extract that is higher in flavanols ( monomers , dimers and trimers ) than its unprocessed counterpart . FRLFE exerts antioxidant activities in vitro and is expected to protect against inflammation and tissue damage . However , the physiological effects of FRLFE intake have not been explored in vivo . The aim of this study was to examine the effects of FRLFE supplementation on inflammation and tissue damage in young athletes during intense physical training . Twenty healthy male long-distance runners at a university were r and omly assigned to receive FRLFE or placebo in a double-blind manner . Blood and serum parameters associated with inflammation , tissue damage and oxidative stress were evaluated before ( pre-training ) , during ( mid-training ) and after ( post-training ) a 2-month training period . Some parameters , including the white blood cell count , were significantly modified by FRLFE supplementation . Compared with the placebo group , the change in the serum interleukin-6 level between pre- and mid-training were significantly lower in the FRLFE group , while the change in the transforming growth factor-β level between pre- and post-training was significantly greater in the FRLFE group . These findings suggest that FRLFE supplementation may suppress inflammation or tissue damage caused by high-intensity exercise training BACKGROUND AND AIMS Public health campaigns recommend increased fruit and vegetable ( FV ) consumption as an effective means of cardiovascular risk reduction . During an 8 week r and omised control trial among hypertensive volunteers , we noted significant improvements in endothelium-dependent vasodilatation with increasing FV consumption . Circulating indices of inflammation , endothelial activation and insulin resistance are often employed as alternative surrogates for systemic arterial health . The responses of several such biomarkers to our previously described FV intervention are reported here . METHODS AND RESULTS Hypertensive volunteers were recruited from medical outpatient clinics . After a common 4 week run-in period during which FV consumption was limited to 1 portion per day , participants were r and omised to 1 , 3 or 6 portions daily for 8 weeks . Venous blood sample s for biomarker analyses were collected during the pre and post-intervention vascular assessment s. A total of 117 volunteers completed the 12 week study . Intervention-related changes in circulating levels of high sensitivity C-reactive protein ( hsCRP ) , soluble intracellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , von Willebr and factor ( vWF ) and plasminogen activator inhibitor-1 ( PAI-1 ) did not differ significantly between FV groups . Similarly , there were no significant between group differences of change in homeostasis model assessment ( HOMA ) scores . CONCLUSIONS Despite mediating a significant improvement in acetylcholine induced vasodilatation , increased FV consumption did not affect a calculated measure of insulin resistance or concentrations of the circulating biomarkers measured during this study . Functional indices of arterial health such as endothelium-dependent vasomotion are likely to provide more informative cardiovascular end-points during short-term dietary intervention trials Based on the existing data in grapes and wine , the aim of the present study was to investigate the probability that raisins improve clinical features and markers of oxidative stress , inflammation and arterial function in healthy smokers . Thirty-six apparently healthy smokers were recruited to an open-label and r and omized , controlled , 4-week prospect i ve intervention . All participants were reported to consume less than the recommended amount of five servings fruits and vegetables daily . Participants in the intervention were instructed to consume raisins equal to five fruit servings ( 90g/d ) . Anthropometric and blood pressure ( BP ) measurements , assessment of dietary intake , and fasting blood draws were conducted at baseline and at week 4 . Biochemical ( glucose , lipids , liver enzymes ) , inflammation [ C-reactive protein ( CRP ) , leptin ] , oxidative stress [ Malondialdehyde ( MDA ) , Advanced oxidation protein products ( AOPPs ) ] and arterial function markers [ Flow-mediated dilatation ( FMD ) , Pulse wave velocity ( PWV ) , Intercellular adhesion molecule-1 ( ICAM-1 ) , Nitric oxide ( NO ) ] were assessed pre- and post-intervention . Baseline characteristics did not differ between the intervention and control arm . No effect of daily raisin consumption was observed on markers assessed between baseline and week 4 in either arm . Regarding vegetable consumption , no difference was observed in either group between baseline and post-intervention ; however , as expected , a significant increase was reported in the intervention arm in fruit consumption between baseline and end point ( p<0.001 ) and between two arms post-intervention ( p<0.001 ) . When analyzing according to age , ICAM-1 levels significantly decreased in subjects > 30years ( n=8 ) in intervention arm ( 390.1±17.6 to 302.2±11ng/mL , p=0.004 ) . After analysis of the data for sex , women in intervention ( n=5 ) decreased significantly diastolic BP ( 74.6±4.2 to 67.4±2.6mg/dL , p=0.043 ) , total cholesterol ( 175.8±7 to 166.6±6.6mg/dL , p<0.001 ) and LDL-cholesterol ( 96.2±9.6 to 89±10.5mg/dL , p=0.012 ) . However , due to the small sample size in the above , no safe conclusions can be exported The study was design ed to determine the effect of thirty days of pomegranate extract oral supplementation on plasma inflammatory and oxidative stress biomarkers as well as serum metabolic profiles , in overweight and obese individuals . In this r and omized , double-blind , placebo-controlled study 48 obese and overweight participants were r and omly assigned to receive either 1000 mg of pomegranate extract , or a placebo , daily for 30 days . At baseline , and after 30 days of treatment , anthropometric parameters , dietary intake , plasma concentrations of malondialdehyde , interleukin-6 and hyper sensitive-C reactive protein and levels of serum lipids , glucose and insulin were assessed . Thirty days of PE supplementation result ed in a significant decrease in mean serum levels of glucose , insulin , total cholesterol , LDL-C , and plasma MDA , IL-6 and hs-CRP . HDL-C significantly increased following the PE versus the PL intervention . Our study suggests that pomegranate extract consumption may reduce complications linked with obesity BACKGROUND The cranberry produces antimicrobial compounds such as proanthocyanidines in response to microbial invasion . In vitro it is able to prevent growth , adhesion or biofilm formation of a large number of bacteria , while clinical ly , cranberry juice has been shown to prevent urinary tract infections ( UTI ) in women . However , the effect of cranberry on bacterial colonization more widely has not been evaluated . We were interested in study ing cranberry juice in children since many children with recurrent UTI need long-term antimicrobial prophylaxis and would benefit from an alternative . OBJECTIVE To evaluate the effect of cranberry juice on nasopharyngeal and colonic bacterial flora , to evaluate how well cranberry juice is accepted by children and to evaluate its effect on infectious diseases and related symptoms . DESIGN Children ( mean age 4.3 years ) in day care centers were r and omized to receive either cranberry juice ( n=171 ) or a placebo ( n=170 ) for 3 months . Bacterial sample s were collected before and after the intervention and analyzed for both respiratory bacterial pathogens and enteric fatty acid composition , reflecting changes in the colonic bacterial flora . Infectious diseases and their symptoms were monitored using symptom diaries . Compliance was evaluated as the number of drop-outs during the trial and by counting the numbers of doses taken . RESULTS The carriage of respiratory bacteria did not change significantly during the intervention , while fecal fatty acid composition changed significantly with time ( P<0.001 ) but did not differ between the groups ( P>0.05 ) . Cranberry juice had no effect on common infectious diseases or their symptoms . The cranberry juice was well accepted : the number of drop-outs in 3 months was 18 ( 11 % ) in the cranberry group and 11 ( 7 % ) in the placebo group , and most of the doses were taken as instructed , 145 ( 88 % ) and 129 ( 77 % ) children , respectively , taking at least 90 % of the doses . CONCLUSIONS Cranberry juice was well accepted by the children , but led to no change in either the bacterial flora in the nasopharynx or the bacterial fatty acid composition of stools . Thus cranberries seem to have beneficial effect on urinary health only and this is not compromised by other unexpected antimicrobial effects Purpose Bilberries are abundant in polyphenols . Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases . We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease ( CVD ) . Methods In a r and omized controlled trial , participants consumed either bilberry juice ( n = 31 ) or water ( n = 31 ) for 4 weeks . Results Supplementation with bilberry juice result ed in significant decreases in plasma concentrations of C-reactive protein ( CRP ) , interleukin (IL)-6 , IL-15 , and monokine induced by INF-γ ( MIG ) . Unexpectedly , an increase in the plasma concentration of tumor nuclear factor-α ( TNF-α ) was observed in the bilberry group . CRP , IL-6 , IL15 , MIG , and TNF-α are all target genes of nuclear factor- kappa B ( NF-κB ) , —a transcription factor that is crucial in orchestrating inflammatory responses . Plasma quercetin and p-coumaric acid increased in the bilberry group , otherwise no differences were observed for clinical parameters , oxidative stress or antioxidant status . Furthermore , we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-κB activation in a monocytic cell line . We observed that quercetin , epicatechin , and resveratrol inhibited NF-κB activation . Conclusions These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes . Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted BACKGROUND Fruit and vegetable ( FV ) intake , which is often low in older people , is associated with reduced chronic disease risk . OBJECTIVE We determined whether increased FV intake improves measures of immune function . DESIGN We conducted a r and omized controlled trial ( The Ageing and Dietary Intervention Trial ) in 83 healthy volunteers aged 65 - 85 y with low FV intakes ( ≤2 portions/d ) ; 82 subjects completed the intervention . Participants were assigned to continue their normal diets or to consume ≥5 FV portions/d for 16 wk . At 12 wk , tetanus toxoid ( 0.5 mL intramuscular ) and Pneumovax II vaccine ( 0.5 mL intramuscular ; both vaccines from Sanofi Pasteur ) were administered . FV intake was monitored by using diet histories , and biomarkers of nutritional status were assessed . The primary endpoint was the antibody response to vaccination . Specific antibodies binding to tetanus toxoid ( total IgG ) and pneumococcal capsular polysaccharide ( total IgG and IgG2 ) were assessed at baseline and 16 wk . Participants were recruited between October 2006 and June 2008 . RESULTS The change in FV consumption differed significantly between groups [ mean change in number of portions ( 95 % CI ) : in the 2-portion/d group , 0.4 portions/d ( 0.2 , 0.7 portions/d ) ; in the 5-portion/d group , 4.6 portions/d ( 4.1 , 5.0 portions/d ) ; P < 0.001 ) ] and also in micronutrient status . Antibody binding to pneumococcal capsular polysaccharide ( total IgG ) increased more in the 5-portion/d group than in the 2-portion/d group [ geometric mean ( 95 % CI ) of the week 16:baseline ratio : 3.1 ( 2.1 , 4.4 ) and 1.7 ( 1.3 , 2.1 ) , respectively ; P = 0.005 ) ] . There was no significant difference in the increases in antibody binding to tetanus toxoid . CONCLUSION Increased FV intake improves the Pneumovax II vaccination antibody response in older people , which links an achievable dietary goal with improved immune function Former smokers are at increased risk for cardiovascular disease . We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk , inflammation , and oxidative stress in former smokers . We also determined the extent these effects were associated with polyphenol bioavailability . A 12-week , r and omized , placebo-controlled trial was conducted in 49 healthy adult former smokers ( n = 24/placebo , n = 25/aronia ) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids , blood pressure , biomarkers of inflammation and oxidative stress , and lipid transport genes of peripheral blood mononuclear cells . The primary outcome was change in low-density lipoprotein cholesterol ( LDL-C ) from baseline , and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion . Aronia consumption reduced fasting plasma total cholesterol by 8 % ( P = .0140 ) , LDL-C by 11 % ( P = .0285 ) , and LDL receptor protein in peripheral blood mononuclear cells ( P = .0036 ) at 12 weeks compared with the placebo group . Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside , 3-(4-hydroxyphenyl ) propionic acid , and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group . Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress . Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation . The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside , its methylated metabolite . This trial was registered at Clinical Trials.gov as NCT01541826 BACKGROUND & AIMS Earlier studies show that dietary bioactive compounds can modify proliferation of γδ-T cells . Garlic contains numerous compounds that have this potential and , in addition , has been shown to influence NK cell function . Our primary aim was to demonstrate that aged garlic extract could modify these immune cells . METHODS A r and omized , double-blind , placebo-controlled parallel intervention study recruited 120 healthy subjects ( 60 per group ) to determine the effect of aged garlic extract supplementation ( 2.56 g/d ) on immune cell proliferation and cold and flu symptoms . RESULTS After 45 d of consuming an encapsulated aged garlic extract , γδ-T cells ( p = 0.039 , n = 56 ) and NK cells ( p = 0.043 , n = 56 ) were shown to proliferate better compared to placebo . After 90 d of supplementation , illness diary entries showed that the incidence of colds and flu , a secondary outcome , were not statistically different ; however , the group consuming the aged garlic extract appeared to have reduced severity as noted by a reduction in the number of symptoms reported ( 21 % fewer , p < 0.001 , z-test of proportions ) , a reduction in the number of days ( 61 % fewer , p < 0.001 , z-test ) and incidences ( 58 % fewer p < 0.001 , z-test ) where the subjects functioned sub-optimally and the number of work/school days missed due to illness ( 58 % fewer , p = 0.035 , z-test ) . CONCLUSIONS These results suggest that supplementation of the diet with aged garlic extract may enhance immune cell function and that this may be responsible , in part , for reduced severity of colds and flu Purpose Wild blueberries ( WB ) ( Vaccinium angustifolium ) are rich sources of polyphenols , such as flavonols , phenolic acids and anthocyanins ( ACNs ) , reported to decrease the risk of cardiovascular and degenerative diseases . This study investigated the effect of regular consumption of a WB or a placebo ( PL ) drink on markers of oxidative stress , inflammation and endothelial function in subjects with risk factors for cardiovascular disease . Methods Eighteen male volunteers ( ages 47.8 ± 9.7 years ; body mass index 24.8 ± 2.6 kg/m2 ) received according to a cross-over design , a WB ( 25 g freeze-dried powder , providing 375 mg of ACNs ) or a PL drink for 6 weeks , spaced by a 6-week wash-out . Endogenous and oxidatively induced DNA damage in blood mononuclear cells , serum interleukin levels , reactive hyperemia index , nitric oxide , soluble vascular adhesion molecule concentration and other variables were analyzed . Results Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases ( from 12.5 ± 5.6 % to 9.6 ± 3.5 % , p ≤ 0.01 ) and the levels of H2O2-induced DNA damage ( from 45.8 ± 7.9 % to 37.2 ± 9.1 % , p ≤ 0.01 ) , while no effect was found after the PL drink . No significant differences were detected for markers of endothelial function and the other variables under study . Conclusions In conclusion , the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage . Future studies should address in greater detail the role of WB in endothelial function . This study was registered at www.is rct n.org as IS RCT N47732406 Individuals with obesity and metabolic syndrome ( MetS ) are at increased risk of cardiovascular disease , in part due to heightened inflammatory/oxidative processes . Results from epidemiologic and experimental studies suggest that citrus , and grapefruit in particular , may have a role in promoting vascular health , although clinical trial data are lacking . Here , we evaluated the anti-inflammatory/antioxidant effects of habitual grapefruit consumption in 69 overweight/obese men and women and in a sub sample of participants with MetS ( n = 29 ) . Participants were r and omly assigned to either a grapefruit group in which they consumed a low bioactive diet plus 1.5 grapefruit/d for 6 wk ( n = 37 , n = 14 with MetS ) or to a control condition in which a low bioactive diet devoid of citrus was consumed ( n = 32 , n = 15 with MetS ) . Plasma soluble vascular adhesion molecule-1 ( sVCAM-1 ) , plasma high-sensitivity C-reactive protein ( hsCRP ) , and urinary F2-isoprostanes were evaluated before and after the intervention phase . F2-isoprostane concentrations were not different in the grapefruit versus control arm after the intervention ( 12.4 ± 6.4 vs. 15.9 ± 9.0 ng/mg creatinine , P = 0.16 ) , whereas plasma hsCRP concentrations tended to be lower in the grapefruit versus control arm postintervention ( 2.1 ± 1.5 vs. 2.8 ± 2.0 mg/L , P = 0.09 ) . In adults with MetS , grapefruit consumption tended to result in lower postintervention F2-isoprostane concentrations compared with the control condition ( 12.0 ± 4.5 vs. 18.3 ± 10.9 ng/mg creatinine , P = 0.06 ) . Furthermore , those with high baseline F2-isoprostane concentrations experienced significant reductions in this biomarker in response to grapefruit consumption ( P = 0.021 ) . Change in sVCAM-1 concentrations did not vary by treatment arm nor were there differences between arms postintervention . These results suggest that intake of grapefruit twice daily for 6 wk does not significantly reduce inflammation and oxidative stress , although there is a suggestion of favorable modulation of oxidative stress in overweight and obese adults with MetS or those with high baseline urine F2-isoprostane concentrations BACKGROUND Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk . The flavonoids epicatechin ( in cocoa and tea ) and quercetin ( in tea ) probably play a role by reducing endothelial dysfunction and inflammation , 2 main determinants of atherosclerosis . OBJECTIVE We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation . METHODS Thirty-seven apparently healthy (pre)hypertensive men and women ( 40 - 80 y ) participated in a r and omized , double-blind , placebo-controlled crossover trial . Participants ingested (-)-epicatechin ( 100 mg/d ) , quercetin-3-glucoside ( 160 mg/d ) , or placebo capsules for a period of 4 wk , in r and om order . Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period . The differences in changes over time between the intervention and placebo periods ( Δintervention - Δplacebo ) were calculated and tested with a linear mixed model for repeated measures . RESULTS Epicatechin changed Δepicatechin - Δplacebo for soluble endothelial selectin ( sE-selectin ) by -7.7 ng/mL ( 95 % CI : -14.5 , -0.83 ; P = 0.03 ) but did not significantly change this difference ( -0.30 ; 95 % CI : -0.61 , 0.01 ; P = 0.06 ) for the z score for endothelial dysfunction . Quercetin changed Δquercetin - Δplacebo for sE-selectin by -7.4 ng/mL ( 95 % CI : -14.3 , -0.56 ; P = 0.03 ) , that for IL-1β by -0.23 pg/mL ( 95 % CI : -0.40 , -0.06 ; P = 0.009 ) , and that for the z score for inflammation by -0.33 ( 95 % CI : -0.60 , -0.05 ; P = 0.02 ) . CONCLUSIONS In (pre)hypertensive men and women , epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function . Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation . This trial was registered at clinical trials.gov as NCT01691404 BACKGROUND Observed associations between increased fruit and vegetable ( F&V ) consumption , particularly those F&Vs that are rich in flavonoids , and vascular health improvements require confirmation in adequately powered r and omized controlled trials . OBJECTIVE This study was design ed to measure the dose-response relation between high-flavonoid ( HF ) , low-flavonoid ( LF ) , and habitual F&V intakes and vascular function and other cardiovascular disease ( CVD ) risk indicators . DESIGN A single-blind , dose-dependent , parallel r and omized controlled dietary intervention study was conducted . Male and female low-F&V consumers who had a ≥ 1.5-fold increased risk of CVD ( n = 174 ) were r and omly assigned to receive an HF F&V , an LF F&V , or a habitual diet , with HF and LF F&V amounts sequentially increasing by 2 , 4 , and 6 ( + 2 , + 4 , and + 6 ) portions/d every 6 wk over habitual intakes . Microvascular reactivity ( laser Doppler imaging with iontophoresis ) , arterial stiffness [ pulse wave velocity , pulse wave analysis ( PWA ) ] , 24-h ambulatory blood pressure , and biomarkers of nitric oxide ( NO ) , vascular function , and inflammation were determined at baseline and at 6 , 12 , and 18 wk . RESULTS In men , the HF F&V diet increased endothelium-dependent microvascular reactivity ( P = 0.017 ) with + 2 portions/d ( at 6 wk ) and reduced C-reactive protein ( P = 0.001 ) , E-selectin ( P = 0.0005 ) , and vascular cell adhesion molecule ( P = 0.0468 ) with + 4 portions/d ( at 12 wk ) . HF F&Vs increased plasma NO ( P = 0.0243 ) with + 4 portions/d ( at 12 wk ) in the group as a whole . An increase in F&Vs , regardless of flavonoid content in the groups as a whole , mitigated increases in vascular stiffness measured by PWA ( P = 0.0065 ) and reductions in NO ( P = 0.0299 ) in the control group . CONCLUSION These data support recommendations to increase F&V intake to ≥ 6 portions daily , with additional benefit from F&Vs that are rich in flavonoids , particularly in men with an increased risk of CVD |
11,292 | 30,586,451 | This review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia , whilst evidence regarding the association with other measures of glycaemic control is mixed . | INTRODUCTION Type 2 diabetes ( T2D ) is a major health priority worldwide and the majority of people with diabetes live with multimorbidity ( MM ) ( the co-occurrence of ≥2 chronic conditions ) .
The aim of this systematic review was to explore the association between MM and all-cause mortality and glycaemic outcomes in people with T2D . | Reports on the relationship between comorbidity and glycemia control in diabetic patients are conflicting and the method of measuring comorbidity varies widely among studies . The aim of the present study was to evaluate the relationship between diabetes control and comorbidity , taking into account all comorbidities and their severity , in a primary care setting . We performed a retrospective descriptive study based on chart review of 96 r and omly selected type 2 diabetic patients . Comorbidity was measured with the cumulative illness rating scale ( CIRS ) , an exhaustive comorbidity index . Diabetes was considered as controlled if the mean value of two measurements of glycosylated hemoglobin A ( HbA1c ) was less than 7 % . Taking diabetes control as the dependent variable , its relationship with the CIRS score , age , sex , diabetes duration , and diabetes-related complications was explored . Diabetes control was not significantly related with the CIRS score , age , sex or diabetes severity . Diabetes duration was the only variable significantly related to diabetes control . Our study suggests that comorbidity measured with the CIRS in patients with type 2 diabetes is not a factor that prevents the achievement of a good glycemia control Diabetes mellitus is a leading cause of death in the United States and is associated with microvascular and macrovascular complications . Approximately 29.1 million persons , or 9.3 % of the U.S. population , have type 2 diabetes ( 1 ) . In 2012 , the total direct and indirect costs associated with diabetes in the United States were $ 245 billion ( 1 ) . Markedly elevated glucose levels can result in subacute symptoms , such as polyuria , polydipsia , weight loss , and dehydration . Over time , the metabolic derangements associated with diabetes may lead to vision loss , painful neuropathy or sensory loss , foot ulcers , amputations , myocardial infa rct ions , strokes , and end-stage renal disease . Lowering blood glucose may decrease risk for complications , but lowering strategies come with harms , patient burden , and costs . Blood glucose can be measured in various ways , including the hemoglobin A1c ( HbA1c ; also called glycosylated or glycated hemoglobin ) level , which approximates average blood glucose control over about 3 months . As with all laboratory tests , HbA1c measurements are associated with variability ( 2 ) and can vary further with race and ethnicity ( 35 ) . Guidelines have historically recommended initiation or intensification of pharmacologic therapy to achieve specific HbA1c targets , depending on the population in question . The ideal target that optimally balances benefits and harms remains uncertain . Guidance Statement Focus and Target Population The purpose of this American College of Physicians ( ACP ) guidance statement is to critically review the available guidelines from various organizations and the evidence included therein to assist clinicians in making decisions about targets when using pharmacologic therapy in adults with type 2 diabetes . Recent data suggesting that newer agents reduce cardiovascular morbidity and mortality in high-risk patients with type 2 diabetes have prompted calls for a fundamental shift in diabetes management . Some anticipate that treatment decisions will eventually be based more on cardiovascular risk than achievement of specific HbA1c targets , analogous to recent changes in lipid management . However , for the foreseeable future , glycemic targets will continue to influence management decisions by front-line clinicians ( 6 ) . This statement focuses on the benefits and harms of targeting lower versus higher HbA1c levels and does not cover use of specific medications outside of their use to achieve HbA1c targets . The intended audience is all clinicians , and the target population is nonpregnant adults with type 2 diabetes . Methods The Clinical Guidelines Committee ( CGC ) of ACP develops guidance statements on topics where several conflicting guidelines are available . We provide clinicians with a rigorous review of the guidelines and the evidence they include . We then adopt the clinical recommendations if we agree with their evaluation of benefits and harms or adapt them if changes are needed based on our assessment of the recommendations and evidence . Data Sources and Guideline Selection We search ed the National Guideline Clearinghouse and the Guidelines International Network library ( May 2017 ) for guidelines on recommended HbA1c targets in the treatment of type 2 diabetes in nonpregnant outpatient adults . We included guidelines that were developed by national organizations , were published in English , and targeted the correct population . We review ed titles and abstract s and excluded guidelines that were modified or adapted from other organizations or addressed specific population s ( such as pregnant women or patients with kidney disease ) . Our search yielded guidelines from the National Institute for Health and Care Excellence ( NICE ) ( 7 ) and the Institute for Clinical Systems Improvement ( ICSI ) ( 8) . On the basis of the knowledge and expertise of ACP CGC members , we also selected the following 4 guidelines not identified in either data base at the time of the search but commonly used in clinical practice : the American Association of Clinical Endocrinologists and American College of Endocrinology ( AACE/ACE ) guideline ( 9 ) , the American Diabetes Association ( ADA ) guideline ( 10 ) , the Scottish Intercollegiate Guidelines Network ( SIGN ) guideline ( 11 ) , and the U.S. Department of Veterans Affairs and Department of Defense ( VA/DoD ) guideline ( 12 ) . Quality Assessment Six co authors independently review ed and assessed each guideline using the AGREE II ( Appraisal of Guidelines for Research and Evaluation II ) instrument ( 13 ) . This instrument asks 23 questions in the following 6 domains : scope and purpose , stakeholder involvement , rigor of development , clarity of presentation , applicability , and editorial independence . The authors scored each guideline independently , and the scores were compared ( Appendix Figure and Appendix Table 1 ) . Authors then provided a summary determination of whether they would recommend this guideline for use by recording yes , no , or yes with modifications . Appendix Figure . Mean AGREE II scores for items in each domain across the 6 review ers . Each question was rated on a Likert scale with a minimum of 1 point and a maximum of 7 points . The scores were averaged for each of the 6 review ers . Error bars represent calculated st and ard deviation . AACE/ACE = American Association of Clinical Endocrinologists and American College of Endocrinology ; ADA = American Diabetes Association ; AGREE II = Appraisal of Guidelines for Research and Evaluation II ; GDG = guideline development group ; ICSI = Institute for Clinical Systems Improvement ; NICE = National Institute for Health and Care Excellence ; SIGN = Scottish Intercollegiate Guidelines Network ; VA/DoD = U.S. Department of Veterans Affairs and Department of Defense . Appendix Table 1 . Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment Peer Review The draft guidance statement was peer- review ed through Annals of Internal Medicine and was posted online for comments from ACP Regents and Governors , who represent ACP members at the regional level . The final guidance statement incorporated comments from peer review ers and ACP Regents and Governors . Public Panel Review The development of this guidance statement also included perspectives , values , and preferences of 2 CGC members who represent the public and a 7-member public panel . Summary of Evaluated Guidelines Using the AGREE II Instrument We review ed and rated 6 guidelines ( AACE/ACE [ 9 ] , ADA [ 10 ] , ICSI [ 8 ] , NICE [ 7 ] , SIGN [ 11 ] , and VA/DoD [ 12 ] ) , focusing solely on sections addressing HbA1c targets in patients with type 2 diabetes . Appendix Table 1 shows the detailed scaled domain scores and average quality ratings for each guideline , and the Appendix Figure shows average AGREE II scores for each item in each of the 6 domains . The fundamental difference between high- and low-scoring guidelines was methodology . The 2 lowest-scoring guidelines , AACE/ACE and ADA , scored lowest on stakeholder involvement , applicability , editorial independence , and scientific rigor . A systematic review is the backbone for any trustworthy guideline , but some guidelines might not be based on a systematic review or may not have made the review publicly available ( 14 , 15 ) . Several factors were important in considering guideline quality . For example , although many guidelines described benefits , adverse effects , and the strength and limitations of evidence or linked the evidence to the recommendation , they often inadequately described how they had considered or weighted these factors in developing the final recommendations . The guidelines frequently relied on selective reporting of studies or outcomes and focused on relative versus absolute effects and asymptomatic surrogate measures rather than patient-centered health outcomes . All of the review ed guidelines recommend individualizing HbA1c targets on the basis of patient characteristics , such as comorbid conditions and risk for hypoglycemia ( Appendix ) . The ADA and SIGN guidelines recommend a target of 7 % for the general population , whereas AACE/ACE recommends 6.5 % ( if it can be achieved safely ) . The NICE guideline specifies 6.5 % or 7 % , depending on the patient 's treatment regimen . Both ICSI and VA/DoD recommend target ranges . The ICSI guideline recommends less than 7 % to less than 8 % based on patient factors , whereas the VA/DoD recommends the following target ranges based on life expectancy and comorbid conditions : 6 % to 7 % for patients with a life expectancy greater than 10 to 15 years and no or mild microvascular complications ; 7 % to 8.5 % for those with established microvascular or macrovascular disease , comorbid conditions , or a life expectancy of 5 to 10 years ; and 8 % to 9 % for those with a life expectancy less than 5 years , significant comorbid conditions , advanced complications of diabetes , or difficulties in self-management attributable to mental status , disability , or other factors ( 12 ) . All guidelines recognize that HbA1c targets can be higher in patients with comorbid conditions and limited life expectancy . We looked into the evidence presented in these guidelines , specifically 5 large , long-term r and omized trials with a treat-to-target strategy and corresponding reports on extended follow-up ( 1623 ) . We summarize below the individual studies and result ing benefits and harms . Note that recent studies evaluating the effectiveness and safety of several newer diabetes drugs ( for example , recently approved sodiumglucose cotransporter-2 inhibitors , dipeptidyl peptidase-4 inhibitors , and glucagon-like peptide-1 receptor agonists ) were not considered in guideline sections pertaining to HbA1c targets because these studies were not design ed to evaluate treat-to-target strategies . Therefore , their findings are not described here . Benefits and Harms of Lower HbA1c Targets : Evidence From Clinical Trials Five large , long-term r and omized controlled trials investigated intensive ( achieved HbA1c levels , 6.3 % to 7.4 % ) versus less intensive ( achieved HbA1c levels , 7.3 % to 8.4 % ) OBJECTIVE To determine the relationship between social support and certain indicators of physical and mental wellbeing in older adults with type 2 diabetes . MATERIAL AND METHODS We undertook a population -based cross sectional study of 705 adults with type 2 diabetes from the Instituto Mexicano del Seguro Social ( IMSS ) . Participants were r and omly selected from a list of diabetic patients located in the south of Mexico City . Physical and mental wellbeing were assessed through three indicators : 1 ) Health related quality of life ( HRQL ) ; 2 ) depressive symptomatology , and 3 ) glycemic control . Level of social support level was determined using the The Social Support Health Survey instrument . Multiple linear regression models were used to analyze the independent association of social support with the physical and mental wellbeing indicators , controlling for progression time , diabetes complications , co-morbidity and socio-demographic variables . RESULTS High levels of social support were reported by 64 % of participants . Social support and HRQL increased in direct proportion : the more social support a participant reported the less depressive distress and better fasting glucose levels they showed . The results maintained their significance in the four social support subscales , with the exception of affectionate and emotional or informational support subscales , which were not significantly correlated with fasting glucose . Multiple linear regression analyses showed that better levels of social support are associated with improved HRQL ( beta = 0.12 ) , less incidence of depressive symptoms ( beta = -0.20 ) and lower fasting glucose ( beta = -0.10 ) . CONCLUSIONS Our findings suggest that greater levels of social support may improve certain indicators of physical and mental wellbeing in older adults with type 2 diabetes , regardless of the presence of diabetes complications and other chronic pathologies . Thus , promoting social support for the IMSS ' diabetic patients could be a useful intervention The objective of this study was to develop a prospect ively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies . A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients . The 1-yr mortality rates for the different scores were : " 0 " , 12 % ( 181 ) ; " 1 - 2 " , 26 % ( 225 ) ; " 3 - 4 " , 52 % ( 71 ) ; and " greater than or equal to 5 " , 85 % ( 82 ) . The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up . The percent of patients who died of comorbid disease for the different scores were : " 0 " , 8 % ( 588 ) ; " 1 " , 25 % ( 54 ) ; " 2 " , 48 % ( 25 ) ; " greater than or equal to 3 " , 59 % ( 18 ) . With each increased level of the comorbidity index , there were stepwise increases in the cumulative mortality attributable to comorbid disease ( log rank chi 2 = 165 ; p less than 0.0001 ) . In this longer follow-up , age was also a predictor of mortality ( p less than 0.001 ) . The new index performed similarly to a previous system devised by Kaplan and Feinstein . The method of classifying comorbidity provides a simple , readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies . Further work in larger population s is still required to refine the approach because the number of patients with any given condition in this study was relatively small AIMS This study aims to investigate the distribution of underlying-causes-of-death ( UCOD ) among deceased patients with type 2 diabetes mellitus ( DM ) in Taiwan and assess the influence of socio-demographic characteristics on mortality in type 2 DM patients . METHODS A cohort study on patients who sought medical care for type 2 DM from 2000 to 2008 was conducted on 65,599 type 2 DM patients retrieved from the 1-million beneficiaries r and omly selected from Taiwan 's National Health Insurance Data base . The study cohort was then linked to Taiwan 's Mortality Registry to ascertain the patients who died between 2000 and 2009 . We examined the distribution of UCOD in the deceased subjects . The hazard ratios of mortality in relation to socio-demographic characteristics were estimated from Cox proportional hazard model . RESULTS The leading causes of death in type 2 DM included neoplasm ( 22.68 % ) , cardiovascular diseases ( 21.46 % ) , and endocrine diseases ( 20.78 % ) . Male gender and older ages were associated with significantly increased risk of mortality . In addition , lower urbanization and greater co-morbidity score were also significantly associated with an increased risk of mortality with a dose-gradient pattern . CONCLUSIONS Neoplasm accounts for the largest portion ( 22.68 % ) of deaths in type 2 DM patients closely followed by with cardiovascular diseases ( 21.46 % ) . An increased risk of mortality in type 2 DM patients in lower urbanized areas may reflect poor diabetes care in these areas OBJECTIVE To examine demographic , socioeconomic , and biological risk factors for all-cause , cardiovascular , and noncardiovascular mortality in patients with type 2 diabetes over 8 years and to construct mortality prediction equations . RESEARCH DESIGN AND METHODS Beginning in 2000 , survey and medical record information was obtained from 8,334 participants in Translating Research Into Action for Diabetes ( TRIAD ) , a multicenter prospect i ve observational study of diabetes care in managed care . The National Death Index was search ed annually to obtain data on deaths over an 8-year follow-up period ( 2000–2007 ) . Predictors examined included age , sex , race , education , income , smoking , age at diagnosis of diabetes , duration and treatment of diabetes , BMI , complications , comorbidities , and medication use . RESULTS There were 1,616 ( 19 % ) deaths over the 8-year period . In the most parsimonious equation , the predictors of all-cause mortality included older age , male sex , white race , lower income , smoking , insulin treatment , nephropathy , history of dyslipidemia , higher LDL cholesterol , angina/myocardial infa rct ion/other coronary disease/coronary angioplasty/bypass , congestive heart failure , aspirin , β-blocker , and diuretic use , and higher Charlson Index . CONCLUSIONS Risk of death can be predicted in people with type 2 diabetes using simple demographic , socioeconomic , and biological risk factors with fair reliability . Such prediction equations are essential for computer simulation models of diabetes progression and may , with further validation , be useful for patient management OBJECTIVE To compare the ability of commonly used measures of medical comorbidity ( ambulatory care groups [ ACGs ] , Charlson comorbidity index , chronic disease score , number of prescribed medications , and number of chronic diseases ) to predict mortality and health care costs over 1 year . STUDY DESIGN AND SETTING A prospect i ve cohort study of community-dwelling older adults ( n=3,496 ) attending a large primary care practice . RESULTS For predicting health care charges , the number of medications had the highest predictive validity ( R(2)=13.6 % ) after adjusting for demographics . ACGs ( R(2)=16.4 % ) and the number of medications ( 15.0 % ) had the highest predictive validity for predicting ambulatory visits . ACGs and the Charlson comorbidity index ( area under the receiver operator characteristic [ ROC ] curve=0.695 - 0.767 ) performed better than medication-based measures ( area under the ROC curve=0.662 - 0.679 ) for predicting mortality . There is relatively little difference , however , in the predictive validity across these scales . CONCLUSION In an outpatient setting , a simple count of medications may be the most efficient comorbidity measure for predicting utilization and health-care charges over the ensuing year . In contrast , diagnosis-based measures have greater predictive validity for 1-year mortality . Current comorbidity measures , however , have only poor to moderate predictive validity for costs or mortality over 1 year Objective . To estimate cause of death and to identify factors associated with risk of inhospital mortality among patients with T2D . Methods . Prospect i ve cohort study performed in a referral public hospital in Lima , Peru . The outcome was time until event , elapsed from hospital admission to discharge or death , and the exposure was the cause of hospital admission . Cox regression was used to evaluate associations of interest reporting Hazard Ratios ( HR ) and 95 % confidence intervals . Results . 499 patients were enrolled . Main causes of death were exacerbation of chronic renal failure ( 38.1 % ) , respiratory infections ( 35.7 % ) , and stroke ( 16.7 % ) . During hospital stay , 42 ( 8.4 % ) patients died . In multivariable models , respiratory infections ( HR = 6.55 , p < 0.001 ) , stroke ( HR = 7.05 , p = 0.003 ) , and acute renal failure ( HR = 16.9 , p = 0.001 ) increased the risk of death . In addition , having 2 + ( HR = 7.75 , p < 0.001 ) and 3 + ( HR = 21.1 , p < 0.001 ) conditions increased the risk of dying . Conclusion . Respiratory infections , stroke , and acute renal disease increased the risk of inhospital mortality among hospitalized patients with T2D . Infections are not the only cause of inhospital mortality . Certain causes of hospitalization require st and ardized and aggressive management to decrease mortality Background Although a variety of treatment guidelines for Type 2 diabetes patients are available , a majority of patients does not achieve recommended targets . We aim ed to characterise Type 2 diabetes patients from Swiss primary care who miss HbA1c treatment goals and to reveal factors associated with the poorly controlled HbA1c level . Methods Cross-sectional study nested within the cluster r and omised controlled Chronic Care for Diabetes study . Type 2 diabetes patients with at least one HbA1c measurement ≥7.0 % during the last year were recruited from Swiss primary care . Data assessment included diabetes specific and general clinical measures , treatment factors and patient reported outcomes . Results 326 Type 2 diabetes patients from 30 primary care practice s with a mean age 67.1 ± 10.6 years participated in the study . The patients ’ findings for HbA1c were 7.7 ± 1.3 % , for systolic blood pressure 139.1 ± 17.6 mmHg , for diastolic blood pressure 80.9 ± 10.5 mmHg and for low density lipoprotein 2.7 ± 1.1 . 93.3 % of the patients suffered from at least one comorbidity and were treated with 4.8 ± 2.1 different drugs . No determining factor was significantly related to HbA1c in the multiple analysis , but a significant clustering effect of GPs on HbA1c could be found . Conclusions Within our sample of patients with poorly controlled Type 2 diabetes , no “ bullet points ” could be pointed out which can be addressed easily by some kind of intervention . Especially within this subgroup of diabetes patients who would benefit the most from appropriate interventions to improve diabetes control , a complex interaction between diabetes control , comorbidities , GPs ’ treatment and patients ’ health behaviour seems to exist . So far this interaction is only poorly described and understood . Trial registration Current Controlled Trials IS RCT N05947538 BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention . We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) BACKGROUND The efficacy of diabetic medications among patients with multiple comorbidities is not tested in r and omized clinical studies . It is important to monitor the performance of these medications after marketing approvals . OBJECTIVE To investigate the risk of all-cause mortality associated with prescription of hypoglycemic agents . METHODS We retrospectively examined data from 17,773 type 2 diabetic patients seen from March 2 , 1998 , to December 13 , 2010 , in 3 Veterans Administration medical centers . Severity was measured using patients ' inpatient and outpatient comorbidities during the last year of visits . Severity-adjusted logistic regression was used to measure the odds ratio for mortality within the study period . RESULTS Patients ' severity of illness correctly classified mortality for 89.8 % of the patients ( P less than 0.0001 ) . Being younger , married , and white decreased severity adjusted risk of mortality . Exposure to the following medications increased severity adjusted risk of mortality : glyburide ( odds ratio [ OR ] = 1.804 , 95 % CI from 1.518 to 2.145 ) , glipizide ( OR = 1.566 , 95 % CI from 1.333 to 1.839 ) , rosiglitazone ( OR = 1.805 , 95 % CI from 1.378 to 2.365 ) , chlorpropamide ( OR = 3.026 , 95 % CI from 1.096 to 8.351 ) , insulin ( OR = 2.382 , 95 % CI from 2.112 to 2.686 ) . None of the other medications ( metformin , acarbose , glimepiride , pioglitazone , repaglinide , troglitazone , or dipeptidyl peptidase-4 ) were associated with excess mortality beyond what could be expected from the patients ' severity of illness or demographic characteristics . The reported excess mortality could not be explained away by use of other concurrent , nondiabetic classes of medications . CONCLUSION Our findings suggest chlorpropamide , glipizide , glyburide , insulin , and rosiglitazone increased severity-adjusted mortality in veterans with type 2 diabetes . A decision aid that could optimize selection of hypoglycemic medications based on patients ' comorbidities might increase patients ' survival OBJECTIVES To compare death rates of diabetic men and women relative to the general population and to identify sex-specific risk factors for all-cause mortality . STUDY DESIGN AND SETTING S In the current historical prospect i ve cohort study , st and ardized mortality ratios ( SMRs ) were calculated for 19,657 men and women with diabetes in a large Israeli health care organization compared to the mortality in the general population from 1999 to 2003 . In addition , sex-specific survival analyses were performed for men and women separately using baseline data obtained between 1995 and 1999 . RESULTS During the study follow-up ( 90,899 person-years ) , 2,924 deaths were identified . The SMR for diabetic women ( 1.40 ; 95 % confidence interval [ CI ] : 1.33 , 1.47 ) was significantly ( P<0.01 ) higher than for diabetic men ( 1.20 ; 95 % CI : 1.14 , 1.26 ) . Age , glycated hemoglobin , serum creatinine , low-density lipoprotein , high-density lipoprotein , dialysis , use of angiotensin-converting enzyme inhibitors , and insulin were similarly associated with mortality in both sexes . Residing in the south of Israel was related with higher risk among men but with decreased risk among women . CONCLUSIONS The study indicates that diabetes seems to eliminate the relative protection against death usually seen in women . It also suggests that most risk factors are comparable between the sexes , underlining the importance of similarly intensive disease management in diabetic women and in diabetic men OBJECTIVES To assess the role of frailty in predicting death and incident disability in older adults with type 2 diabetes mellitus . DESIGN Prospect i ve cohort study . SETTING Community dwelling . PARTICIPANTS A total of 1825 individuals ≥65 years old recruited between June 2006 and September 2009 were followed for a median of 5.5 years for mortality and 4.98 years for incident functional disability in activities of daily living . Self-reported diabetes , comorbidities ( Charlson index ) , cardio- and cerebrovascular diseases , drug treatments , Frailty Trait Score ( FTS ) and Frailty Index ( FI ) , activities of daily living , heart rate , and blood pressure among others were collected at baseline . MAIN OUTCOME MEASURES Survival analysis ( Kaplan-Meier ) , adjusted Cox proportional-hazards models , and binary logistic regression were used to assess the relationship between frailty , comorbidity , and vascular diseases and time to death and incident disability . RESULTS A total of 363 people had diabetes . Among them , 83 deaths and 84 cases of incident disability occurred during follow-up . People with diabetes died more frequently than those without diabetes [ hazard ratio = 1.36 , 95 % confidence interval ( CI ) 1.06 - 1.75 ; P = .002 ] , showing a poorer functional status at baseline . Survival analysis showed a relationship between frailty quartiles and the risk of death . In the adjusted Cox-models , only age and frailty indices , but not comorbidity or cardio/cerebrovascular diseases , were associated with the risk of death and incident disability after adjusting for measures of frailty . The hazard ratio for death was 1.51 ( 95 % CI 1.28 - 1.77 ) and 1.83 ( 95 % CI 1.49 - 2·26 ) for each 10 points increase in the FTS and FI ; odds ratio for incident disability was 1·64 ( 95 % CI 1.22 - 2.20 ) and 1·35 ( 95 % CI 1.09 - 1.67 ) when using FI and FTS , respectively . CONCLUSIONS Frailty is an important risk factor for death and disability in older adults with diabetes , supporting the recent recommendations that frailty status should be routinely assessed in these patients ABSTRACT Background : People with type 2 diabetes frequently have a variety of related and unrelated chronic conditions . These additional conditions have implication s for patient education , treatment burden and disease management . Objectives : The aim of this study was to examine the nature of multimorbidity , and its impact on GP visits , polypharmacy and glycaemic control as measured by HbA1c , in a cohort of patients with type 2 diabetes attending general practice in Irel and . Methods : A cohort of 424 patients with type 2 diabetes enrolled in a cluster r and omized controlled trial based in Irish general practice was examined . Patient data included : medical conditions , HbA1c , health service utilization , socio-economic status and number of prescribed medications . Results : 90 % of patients had at least one additional chronic condition and a quarter had four or more additional chronic conditions . 66 % of patients had hypertension ; 25 % had heart disease ; and 16 % had arthritis . General practitioner visits and polypharmacy increased significantly with increasing numbers of chronic conditions . When comparing patient self-report with medical records , patients who reported a higher proportion of their conditions had better glycaemic control with a significantly lower HbA1c score . Conclusion : There was a high prevalence of multimorbidity in these patients with type 2 diabetes and the results suggest that glycaemic control is related to patients ’ awareness of their chronic conditions . The variety of conditions emphasizes the complexity of illness management in this group and the importance of maintaining a generalist and multidisciplinary approach to their clinical care BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P<0.001 ) . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . OBJECTIVES To assess the incidence of type 2 diabetes mellitus ( DM ) in patients with heart failure ( HF ) , and to evaluate the effect of new-onset DM and glycemic control on the prognosis of HF patients treated with a contemporary medical regimen . METHODS Prospect i ve study of 5314 HF patients and previously unknown DM during 9 years . Their mean age was 71.8 ± 7.9 years , 53.0 % were women , and 50.2 % had non-systolic HF . During a median follow-up of 56.9 ± 18.2 months , 68.9 % of the patients died , 88.6 % were hospitalized for HF , and 1519 ( 27.3 % ) developed new-onset DM . We propensity-matched those 1519 HF patients with DM , with 1519 HF patients non-diagnosed with DM . RESULTS The age- and sex-adjusted incidence ( per 100 HF patients /years ) of DM in HF patients was 3.20 , higher in women and in patients with non-systolic HF ( p<0.01 ) . Patients with HF and DM and those with a mean HbA1c>7.0 % presented an increased mortality ( HR of death [ CI 95 % ] : 2.44 [ 1.68 - 3.19 ] and , HR : 2.56 [ 1.77 - 3.35 ] , respectively ) , mainly due to an increased cardiovascular mortality ( HR ≥ 2.40 [ 1.46 - 3.34 ] ) ( P<0.001 ) . The rate of hospitalization , of 30-day readmissions , and the number of visits were higher among HF patients with DM or with HbA1c>7.0 % ( p<0.001 ) . These relationships of DM and its poor metabolic control with prognosis were maintained , independently of the gender , the type of HF ( systolic or , non-systolic ) , the comorbidities , and the medication used ( P<0.01 ) . CONCLUSION New-onset diabetes mellitus and its poor metabolic control ( HbA1c>7.0 % ) are associated with a increased mortality and morbidity of patients with heart failure Abstract Objective : To assess health outcomes and the economic burden of hypoglycemia in older patients with type 2 diabetes initiating basal insulin ( BI ) . Research design and methods : Medicare Advantage cl aims data were extracted for patients with type 2 diabetes initiating BI and patients were stratified into two groups : those with medically attended hypoglycemia during the first year of BI treatment ( HG group ) and those without ( non-HG group ) . Main outcome measures were hospitalization , mortality , healthcare utilization and costs 1 year before and 1 year after BI initiation . Results : Of 31,035 patients included ( mean age 72 years [ SD 9.2 ] ) , 3066 ( 9.9 % ; HG group ) experienced hypoglycemia during 1 year post-BI initiation . After adjustment for demographic , comorbidity and medication history , hypoglycemia was associated with risk of hospitalization ( HR 1.59 ; 95 % CI : 1.53–1.65 ) and death ( HR 1.50 ; 95 % CI : 1.40–1.60 ) . Healthcare utilization was higher pre-index and showed greater increases post-BI initiation in the HG vs. the non-HG group . Per-patient healthcare costs were substantially higher for the HG group than the non-HG group , both pre-index ( $ 54,057 vs. $ 30,249 , respectively ) and post-BI initiation ( $ 75,398 vs. $ 27,753 , respectively ) . Conclusions : Based on available cl aims data , hypoglycemia during the first year of BI treatment is associated with risk of hospitalization or death in older people , increasing healthcare utilization and costs . Due to the observational nature of this study , causality can not be attributed , and further prospect i ve studies into the effect of hypoglycemia on health outcomes in this population are warranted Patients with type 2 diabetes are at high risk for several serious health problems , including premature death , cardiovascular disease (CVD),2 blindness , and kidney failure . Moreover , there is a strong positive association between the degree of glycemia , measured as plasma glucose or glycated hemoglobin ( Hb A1c ) , and the above outcomes . Hence , it has been hypothesized that the mortality and morbidity of type 2 diabetes can be reduced with intensive control of glycemia . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial tested this hypothesis by determining whether a therapeutic strategy that targeted a typical Hb A1c value of < 6.0 % , compared with a strategy that targeted an Hb A1c value of 7.0%–7.9 % , would reduce CVD ( 1 ) . The primary outcome was a composite of CVD death , nonfatal myocardial infa rct ion , and nonfatal stroke . Secondary outcomes included all-cause mortality , development and progression of microvascular disease , frequency of severe hypoglycemia , and progression of retinopathy . The trial also tested the effects of intensive blood pressure ( BP ) control and the addition of a fibrate in selected patients . The study r and omized 10 251 participants with well-established type 2 diabetes . Entry criteria included a history of a cardiovascular event or at least 2 risk factors for CVD , and a normal serum creatinine concentration . The trial was not design ed to test the efficacy of any particular medication or combination of medications . What differed between the 2 arms was the glycemic target and consequently the frequency of use of glycemia medications and , to a lesser extent , the dosage . All participants made frequent clinic visits , during which lifestyle education and hypoglycemia prevention were emphasized . Within 8 months after enrollment , the median Hb A1c values in the intensive and st and ard glycemia arms reached 6.4 % and 7.5 % , respectively , and remained stable with a difference between the medians of 1.1 % Context The effectiveness of glycemic control in reducing cardiovascular events among patients with type 2 diabetes is uncertain . Recent analyses of trial data suggest that the benefit of tight control may differ according to a person 's age and comorbid conditions . Contribution This observational study of 2613 patients with type 2 diabetes in 205 practice s in Italy found that tight control was associated with lower risk for cardiovascular events over 5 years in patients with low to moderate , but not high , comorbidity . Caution Observational data can not prove a causal association between glycemic control and outcomes . Implication The relationship of glycemic control and cardiovascular outcomes differs by patients ' level of comorbidity . The Editors Major professional organizations recommend that attaining a hemoglobin A1c ( HbA1c ) value less than 7.0 % may be less appropriate for patients with limited life expectancy , advanced complications , and extensive comorbidity ( 13 ) . Evidence suggests that the benefit of intensive glucose-lowering therapy is not uniform across all patients with type 2 diabetes . Three large r and omized , controlled trials that used HbA1c targets of 6.5 % or lower ( 46 ) each found no association between intensive therapy and an overall reduction in risk for macrovascular complications . However , when data from these and other trials were considered in 2 recent meta-analyses ( 7 , 8) , the investigators observed statistically significant relationships between tight glycemic control and reduced cardiovascular events . Post hoc analyses of data from these clinical trials suggest that benefit from aggressive glycemic control may be confined to younger diabetic patients ( 4 ) and patients without previous heart disease ( 4 , 5 ) . Data from the 10-year posttrial follow-up ( 9 ) to the UKPDS ( United Kingdom Prospect i ve Diabetes Study ) ( 10 ) also showed a reduction in cardiovascular events from intensive glucose-lowering therapy initiated in a young and healthy sample of patients with recently diagnosed type 2 diabetes . Recent decision analyses based on UKPDS risk models suggest that , independent of age , high levels of comorbidity may diminish the benefits of achieving tight control ( 11 ) , owing to the complex interplay of multiple conditions , their treatments , and their burden on patient re sources ( 12 ) . Among the comorbid conditions prevalent among diabetic patients , cardiovascular diseases are the most important contributors to mortality and subsequent cardiovascular events . However , additional conditions , such as chronic lung disease , may also bring functional impairment , treatment burden , and risk for adverse events and may diminish a patient 's likelihood to benefit from tight control ( 13 , 14 ) . In a 5-year observational study of a community-based sample of older patients with type 2 diabetes , we tested whether attaining glycemic control targets of HbA1c levels of 6.5 % or less or 7.0 % or less at baseline provided differential benefits for patients with higher versus lower levels of comorbidity . We further compared the unique contribution of comorbid conditions with that of other risk factors ( such as age or duration of diabetes ) to the differential benefit from glycemic control on future cardiovascular events . Methods Our study , described in detail elsewhere ( 1517 ) , was a 5-year longitudinal observational study ( 1999 to 2004 ) that examined the association of the quality of diabetes care with the incidence of cardiovascular events and mortality . Patients were followed for a median of 4.96 years ( interquartile range , 3.35 to 5.00 years ) . Patients We identified medical practice s in all regions of Italy and selected them according to their willingness to participate in the project . Participating practice s included 101 of approximately 605 eligible diabetes outpatient clinics and 103 of approximately 1000 eligible community-based general practitioners enrolled in a nationwide network of practitioners interested in facilitating research . We considered all patients with type 2 diabetes mellitus ( fasting venous plasma glucose concentration 7.8 mmol/L [ 140 mg/dL ] on 2 separate occasions or treated with antidiabetic drugs ) to be eligible for the project , regardless of age , diabetes duration , or treatment . At the diabetes outpatient clinics , patients were r and omly sample d from clinic rosters and stratified by patient age ( < 65 or 65 years ) . We asked each diabetes outpatient clinic to recruit at least 30 patients . Community-based general practitioners consecutively enrolled only patients for whom they were primarily responsible for diabetes care , up to a maximum of 10 patients . Clinical Measures The main outcome of the study was incident cardiovascular events , defined as any of the following outcomes : angina , myocardial infa rct ion , stroke , transient ischemic attack , coronary revascularization procedures , lower limb complications ( claudication , ulcer , gangrene , amputation , or aorticfemoral revascularization procedures ) , or cardiovascular mortality . Participating physicians certified the occurrence of any cardiovascular event over the 5-year study period , on the basis of study -wide criteria . In addition , participating physicians reported the death of any study patient from any cause ; this information was used to compute total mortality rates . Participating physicians abstract ed demographic and clinical data , including age , body mass index , duration of diabetes , HbA1c level , lipid levels , and blood pressure ( collected and entered into models as continuous variables ) , as well as sex , smoking status and the presence of diabetes complications ( collected and entered into models as categorical variables ) from clinical records and reported these data to the coordinating center at Mario Negri Sud . Because normal ranges for HbA1c varied in the different centers , the percentage change with respect to the upper normal value ( actual value vs. upper limit of normal ) was estimated and multiplied by 6.0 ( 16 ) . Total cholesterol was used as a measure of lipid control because low-density lipoprotein levels were not routinely measured in many of the study patients . We used the last blood pressure value in the clinical record before the data collection point . Data were collected at baseline and at 6-month intervals for 5 years . Measure of Comorbidity We requested that all recruited patients complete the Total Illness Burden Index ( TIBI ) question naire ( 1820 ) . The TIBI , which was specifically developed for office practice population s , uses patient reports to assess the presence and severity of 8 dimensions of comorbid conditions , problems , and diseases ( atherosclerotic heart disease , lung disease , congestive heart failure , arthritis , genitourinary disease , vision loss , gastrointestinal conditions , and foot disease ) by using items similar to those in the traditional review of systems . We scored these responses to assess the severity of the 8 dimensions and then aggregated the scores by using an algorithm that weighted each dimension according to its predicted effect on functional outcomes . We also performed analyses that used a version of the TIBI score that excluded previous cardiovascular events to examine the effects of the noncardiac components of the TIBI on future events . We refer to this version as the noncardiovascular TIBI score . The TIBI can be completed and scored in office practice s for use by physicians at the time of treatment and has been vali date d as a predictor of 3.5-year mortality ( 20 ) and health-related quality of life ( 18 , 19 ) . Statistical Analysis We conducted univariate analyses to describe patient characteristics and reported means and SDs for continuous variables and frequencies and percentages for categorical variables . We calculated the probabilities of incident cardiovascular events by using the KaplanMeier method and carried out comparisons by using the log-rank test . We divided patients into 2 prespecified subgroups at a threshold TIBI score of 12 , which has been demonstrated to discriminate between persons at greater and lesser risk for death ( 20 ) . We defined patients with TIBI scores less than 12 as the low-to-moderate comorbidity subgroup and patients with scores of 12 or greater as the high comorbidity subgroup . To account for the hierarchical nature of the data ( patients clustered within center ) , and to control for possible confounding or clustering by center of variables , we used multivariate Cox proportional hazards regression models , stratified by center , to investigate whether a dichotomized TIBI score was an independent predictor of clinical outcomes . In all analyses , we expressed outcome risk in terms of hazard ratios ( HRs ) with 95 % CIs in models adjusted for age ( as a continuous variable ) and sex ( as a categorical variable ) . To demonstrate that the threshold TIBI score of 12 differentiated patients ' risk both for cardiovascular events and for total mortality in the current sample , we computed hazard ratios for relative risk for each outcome between participants with TIBI scores of 12 or greater and patients with scores less than 12 . To demonstrate that any association observed between comorbidity and outcome risk was not an artifact of the selected TIBI score cut-point , we computed hazard ratios for both cardiovascular event risk and mortality risk by using the TIBI score as a continuous , independent variable . We replicated the analysis by using the noncardiovascular TIBI score to examine its association with future cardiovascular events and mortality . To determine whether the benefit of attaining recommended targets for glycemic control was greater for patients with low-to-moderate or high levels of comorbidity , we tested whether baseline HbA1c levels of 6.5 % or less or 7.0 % or less were associated with lower incidence of cardiovascular events in each comorbidity subgroup . To examine whether any observed association between attaining glycemic control targets and reduced cardiovascular event risk was sensitive |
11,293 | 30,760,293 | The pooled results of UCLA score , SST score , and complications showed that the differences were not statistically significant between the two interventions .
The difference of ASES score and satisfaction rate was statistically significant between arthroscopic repair and biceps tenotomy and tenodesis intervention , and arthroscopic biceps tenotomy and tenodesis treatment was more effective .
Conclusions Both arthroscopic repair and biceps tenotomy and tenodesis interventions had benefits in type II SLAP lesions .
Arthroscopic biceps tenotomy and tenodesis treatment provides better clinical outcome in ASES score and satisfaction rate and comparable complications compared with arthroscopic repair treatment . | Objective Labral repair and biceps tenotomy and tenodesis are routine operations for type II superior labrum anterior posterior ( SLAP ) lesion of the shoulder , but evidence of their superiority is lacking .
We conducted this systematic review and meta- analysis to compare the clinical outcomes of arthroscopic repair versus biceps tenotomy and tenodesis intervention . | The purpose of this study was to evaluate the outcomes of patients undergoing subpectoral biceps tenodesis for bicipital tendonitis with a superior labral anterior-posterior ( SLAP ) tear . Patients undergoing primary subpectoral biceps tenodesis for arthroscopically confirmed SLAP tears with signs or findings of bicipital tendonitis were included . An independent observer collected data prospect ively as part of a data repository , which was then analyzed retrospectively . Primary outcome measures were the American Shoulder and Elbow Surgeons ( ASES ) score and pain relief via visual analog scale ( VAS ) . Secondary outcome measures included the Simple Shoulder Test ( SST ) , Constant , Single Assessment Numeric Evaluation ( SANE ) , and Short Form 12 ( SF-12 ) scores . Twenty-eight patients with a mean±SD age of 43.7±13.4 years and a mean±SD follow-up of 2.0±1.0 years met inclusion criteria . Workers ' compensation was involved with 43 % of cases , and 46 % of the included patients were manual laborers . Eight ( 32 % ) patients were athletes , and 88 % of the athletes were overhead athletes . Intraoperatively , 15 ( 54 % ) patients had type I SLAP tears , 10 ( 36 % ) had type II SLAP tears , 1 ( 3 % ) had a type III SLAP tear , and 2 ( 7 % ) had type IV SLAP tears . Significant improvements were seen in the following outcome measures pre- vs postoperatively : ASES score ( 58±23 vs 89±18 ; P=.001 ) , SST score ( 6.3±3.6 vs 10.6±3.3 ; P=.001 ) , SANE score ( 54±24 vs 88±25 ; P=.003 ) , VAS score ( 3.8±2.0 vs 1.1±1.8 ; P=.001 ) , SF-12 overall score ( 35±6 vs 42±6 ; P=.001 ) , and SF-12 physical component score ( 39±6 vs 50±10 ; P=.001 ) . Overall satisfaction was excellent in 80 % of patients . Subpectoral biceps tenodesis demonstrates excellent clinical outcomes in select patients with SLAP tears . [ Orthopedics . 2015 ; 38(1):e48-e53 . ] Background Labral repair and biceps tenodesis are routine operations for superior labrum anterior posterior ( SLAP ) lesion of the shoulder , but evidence of their efficacy is lacking . We evaluated the effect of labral repair , biceps tenodesis and sham surgery on SLAP lesions . Methods A double-blind , sham-controlled trial was conducted with 118 surgical c and i date s ( mean age 40 years ) , with patient history , clinical symptoms and MRI arthrography indicating an isolated type II SLAP lesion . Patients were r and omly assigned to either labral repair ( n=40 ) , biceps tenodesis ( n=39 ) or sham surgery ( n=39 ) if arthroscopy revealed an isolated SLAP II lesion . Primary outcomes at 6 and 24 months were clinical Rowe score ranging from 0 to 100 ( best possible ) and Western Ontario Shoulder Instability Index ( WOSI ) ranging from 0 ( best possible ) to 2100 . Secondary outcomes were Oxford Instability Shoulder Score , change in main symptoms , EuroQol ( EQ-5D and EQ-VAS ) , patient satisfaction and complications . Results There were no significant between-group differences at any follow-up in any outcome . Between-group differences in Rowe scores at 2 years were : biceps tenodesis versus labral repair : 1.0 ( 95 % CI −5.4 to 7.4 ) , p=0.76 ; biceps tenodesis versus sham surgery : 1.6 ( 95 % CI −5.0 to 8.1 ) , p=0.64 ; and labral repair versus sham surgery : 0.6 ( 95 % CI −5.9 to 7.0 ) , p=0.86 . Similar results —no differences between groups — were found for WOSI scores . Postoperative stiffness occurred in five patients after labral repair and in four patients after tenodesis . Conclusion Neither labral repair nor biceps tenodesis had any significant clinical benefit over sham surgery for patients with SLAP II lesions in the population studied . Trial registration number Clinical Trials.gov identifier : This study compared arthroscopic biceps tenodesis with biceps repair for isolated type II superior labrum anterior and posterior ( SLAP ) lesions in patients older than 35 years . The authors identified isolated type II SLAP lesions that were surgically managed over a 5-year period . Minimum 2-year follow-up data were available for 22 patients who underwent biceps repair ( repair group ) and for 15 patients who underwent a primary biceps tenodesis ( tenodesis group ) . Mean age at surgery was 45.2±5.5 years in the repair group and 52.0±8.0 years in the tenodesis group . In the repair group , functional outcome improved from baseline to final follow-up using the American Shoulder and Elbow Surgeons ( ASES ) ( 47.5 to 87.4 , respectively ; P<.0001 ) and University of California , Los Angeles ( UCLA ) scores ( 18.5 to 31.2 , respectively ; P<.0001 ) . In the tenodesis group , similar findings were observed for the ASES ( 43.4 to 89.9 , respectively ; P<.0001 ) and UCLA scores ( 19.0 to 32.7 , respectively ; P<.0001 ) . No difference was found in functional outcome between the groups . Full range of motion recovery was delayed by approximately 3 months in the repair group compared with the tenodesis group ( P=.0631 ) . Two patients in the repair group required a secondary capsular release . Seventy-seven percent of patients in the repair group and 100 % of patients in the tenodesis group were satisfied and returned to normal activity ( P=.0673 ) . In the current study , individuals older than 35 years with an isolated type II SLAP lesion had a shorter postoperative recovery , a more predictable functional outcome , and a higher rate of satisfaction and return to activity with a biceps tenodesis compared with a biceps repair . Based on these observations , biceps tenodesis is preferable to biceps repair for isolated type II SLAP lesions in nonoverhead athletes older than 35 years Background : There are no studies examining superior labrum anterior and posterior ( SLAP ) repair combined with repair of large to massive rotator cuff tears , and it is unclear whether a combined SLAP repair would lead to better outcomes than biceps tenotomy . Hypothesis : Tenotomy and rotator cuff repair would lead to better outcomes compared with those of combined SLAP and rotator cuff repair . Study Design : Cohort study ; Level of evidence , 2 . Methods : Our study population consisted of 36 patients who had undergone either combined SLAP and rotator cuff repair ( when the biceps was too healthy to cut ; group R = 16 patients ) or tenotomy and rotator cuff repair ( when any fraying or partial tear existed in the biceps tendon ; group T = 20 patients ) for concomitant type II SLAP lesions and large to massive rotator cuff tears . The cuff repair was performed in a single row for both groups . Outcomes were assessed by comparing range of motion as well as Simple Shoulder Test ( SST ) , American Shoulder and Elbow Surgeons ( ASES ) , and University of California , Los Angeles ( UCLA ) scores between the 2 groups . Results : At the 2-year follow-up , both groups demonstrated significant improvements in functional shoulder scores and range of motion . However , group T had better SST scores ( group T , 9.3 ± 1.6 ; group R , 7.8 ± 1.9 ; P = .012 ) , ASES scores ( group T , 88.6 ± 8.9 ; group R , 80.4 ±8.9 ; P = .009 ) , UCLA scores ( group T , 29.6 ± 3.0 ; group R , 26.0 ± 4.2 ; P = .007 ) , and forward flexion ( group T , 145.9 ° ± 13.0 ° ; group R , 132.5 ° ± 15.3 ° ; P = .008 ) . The mean tear size and the degree of preoperative muscle atrophy and fatty infiltration on magnetic resonance imaging were similar between the groups . Conclusion : For patients with concomitant type II SLAP lesions and large to massive rotator cuff tears , the outcomes of simultaneous arthroscopic SLAP and rotator cuff repair were inferior to those of arthroscopic biceps tenotomy and cuff repair in terms of functional shoulder scores and range of motion . Biceps tenotomy and rotator cuff repair may be a more reliable method to address concomitant type II SLAP lesions and large to massive rotator cuff tears in patients , although a r and omized controlled trial is needed to confirm the results Background Arthroscopic management has been recommended for some superior labrum anterior and posterior ( SLAP ) lesions , but no studies have focused on patients over 50 years of age with rotator cuff tear and a type II SLAP lesion . Hypothesis In patients over 50 years of age with an arthroscopically confirmed lesion of the rotator cuff and a type II SLAP lesion , there is no difference between ( 1 ) repair of both lesions and ( 2 ) repair of the rotator cuff tear without repair of the SLAP II lesion but with a tenotomy of the long head of the biceps . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods We recruited 63 patients . In 31 patients , we repaired the rotator cuff and the type II SLAP lesion ( group 1 ) . In the other 32 patients , we repaired the rotator cuff and tenotomized the long head of the biceps ( group 2 ) . Seven patients ( 2 in group 1 and 5 in group 2 ) were lost to final follow-up . Results At a minimum 2.9 years ’ follow-up , statistically significant differences were seen with respect to the University of California , Los Angeles ( UCLA ) score and range of motion values . In group 1 ( SLAP repair and rotator cuff repair ) , the UCLA showed a statistically significant improvement from a preoperative average rating of 10.4 ( range , 6–14 ) to an average of 27.9 ( range , 24–35 ) postoperatively ( P < .001 ) . In group 2 ( biceps tenotomy and rotator cuff repair ) , the UCLA showed a statistically significant improvement from a preoperative average rating of 10.1 ( range , 5–14 ) to an average of 32.1 ( range , 30–35 ) postoperatively ( P < .001 ) There was a statistically significant difference in total postoperative UCLA scores and range of motion when comparing the 2 groups postoperatively ( P < .05 ) . Conclusions There are no advantages in repairing a type II SLAP lesion when associated with a rotator cuff tear in patients over 50 years of age . The association of rotator cuff repair and biceps tenotomy provides better clinical outcome compared with repair of the type II SLAP lesion and the rotator cuff PURPOSE The aims of this prospect i ve cohort study were to assess the long-term results after isolated superior labral repair and to determine whether the results were associated with age . METHODS One hundred seven patients underwent repair of isolated SLAP tears . There were 36 women and 71 men with a mean age of 43.8 years ( range , 20 to 68 years ) . Mean follow-up was 5.3 years ( range , 4 to 8 years ) . Of the patients , 62 ( 57.9 % ) were aged 40 years or older . Follow-up examinations were performed by an independent examiner ; 102 patients ( 95.3 % ) had a 5-year follow-up . RESULTS The Rowe score improved from 62.8 ( SD , 11.4 ) preoperatively to 92.1 ( SD , 13.5 ) at follow-up ( P < .001 ) . Satisfaction was rated excellent/good for 90 patients ( 88 % ) at 5 years . There was no significant difference in the results for patients aged 40 years or older and those aged under 40 years . Difficulty with postoperative stiffness and pain was reported by 14 patients ( 13.1 % ) . CONCLUSIONS Our results suggest that long-term outcomes after isolated labral repair for SLAP lesions are good and independent of age . Postoperative stiffness was registered in 13.1 % of the patients . LEVEL OF EVIDENCE Level IV , therapeutic case series The aim of this study was to determine whether or not detaching the biceps tendon from the glenoid after tenodesis performed with the inclusion of the biceps in the rotator cuff suture results in an improved outcome . From 1999 to 2001 , 22 patients had an arthroscopic rotator cuff repair and associated biceps tendon lesions that were repaired with two new arthroscopic techniques of tenodesis incorporating the biceps tendon in the rotator cuff suture . Patients were r and omised into one of two groups : tenodesis without tenotomy ( group 1 ) and tenodesis with tenotomy ( group 2 ) . Preoperative and postoperative functions were assessed by means of a modified UCLA rating scale and shoulder ROM . The mean follow-up period was 47.2 months ( range 36– 59 ) . In group 1 ( tenodesis without tenotomy ) , eight patients had an excellent postoperative score and three a good postoperative score . The UCLA rating system used for evaluation showed a statistically significant improvement from the preoperative average rating of 10.5 ( 5–15 ) to the postoperative average score of 33 ( 29–35 ) ( P<0.05 ) . In group 2 ( tenodesis with tenotomy ) , the UCLA rating system used for evaluation showed a statistically significant improvement from the preoperative rating of 11.1 to the postoperative score of 32.9 ( P<0.05 ) . No statistically significant difference in the total UCLA scores was found when comparing the repairs performed with or without tenotomy . Follow-up results with regard to ROM were not different between the two groups , and the range of motion was improved in all measured directions . In this series , every patient qualified as having good to excellent results according to the UCLA score . This study suggests that there is no difference between detaching and not detaching the biceps after including it in the repair . RésuméLe but de cette étude est de déterminer si le fait de détacher le tendon du biceps de la cavité glénoïde après ténodèse réalisé avec inclusion du tendon dans la réparation de la coiffe des rotateurs a une influence sur le résultat . De 1999 à 2001 , 22 patients ont eu une réparation de la coiffe des rotateurs sous arthroscopie associée à des lésions du tendon du biceps qui furent réparés avec deux nouvelles techniques arthroscopiques de ténodèse incorporant le biceps dans la réparation de la coiffe . Les patients furent r and omisés en deux groupes : ténodèse sans ténotomie ( groupe 1 ) et ténodèse avec ténotomie ( groupe 2 ) . La fonction préopératoire et post opératoire a été mesurée au moyen de l’échelle UCLA et de la mesure des amplitudes articulaires . La durée moyenne du suivi est de 47.2 mois ( allant de 36 à 59 ) . Dans le groupe 1 ( ténodèse sans ténotomie ) 8 patients ont eu un excellent score post opératoire et 3 un bon score post opératoire . Le score UCLA utilisé pour l’évaluation a montré une amélioration significative avec une moyenne préopératoire de 10.5 ( 5 à 15 ) et une moyenne post opératoire de 33 ( 29 à 35 ) ( P<0.05 ) . Dans le groupe 2 ( ténodèse avec ténotomie ) , le score UCLA utilisé pour l’évaluation montre une différence significative avec un score préopératoire de 11.1 et post opératoire de 32.9 ( P<0.05 ) . Il n’a pas été trouvé de différence significative au niveau du score UCLA qu and on compare les réparations réalisées avec ou sans ténotomies . Les résultats au recul , en ce qui concerne le score amplitude n’étaient pas différents entre les deux groupes et les amplitudes de mouvements étaient améliorées dans toutes les directions . Dans ces séries , tous les patients étaient considérés comme des bons à excellents résultats selon le score UCLA . Cette étude suggère donc qu’il n’y a pas de différence que l’on détache ou pas le long biceps après l’avoir inclus dans la réparation |
11,294 | 25,412,074 | Overall , home haemodialysis reduced 24 hour ambulatory blood pressure and improved uraemic symptoms , but increased treatment-related burden of disease and interference in social activities . | BACKGROUND Home haemodialysis is associated with improved survival and quality of life in uncontrolled studies .
However , relative benefits and harms of home versus in-centre haemodialysis in r and omised controlled trials ( RCTs ) are uncertain .
OBJECTIVES To evaluate the benefits and harms of home haemodialysis versus in-centre haemodialysis in adults with end-stage kidney disease ( ESKD ) . | BACKGROUND The US National Institutes of Health ( NIH ) and Centers for Medicare and Medicaid Services ( CMS ) sponsored a r and omized clinical trial comparing six versus three times per week in-center hemodialysis ( the Frequent Hemodialysis Network [ FHN ] Daily Trial ) , to test the effects of frequent hemodialysis on an array of intermediate outcomes . Herein we report challenges to enrollment and r and omization into the trial . METHODS Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects . Reasons for consent refusal were recorded in a subset of ( 10 out of 65 ) sites . RESULTS The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics , 3481 ( 55 % ) were considered eligible for enrollment , and 3124 ( 90 % ) were approached for consent ; 378 ( 12 % ) consented and 245 were r and omized ( 65 % of those enrolled ) . Prospect i ve subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol . CONCLUSIONS Recruitment into the FHN Daily Trial proved challenging but the goal of 250 r and omized subjects was almost met Provider and patient enthusiasm for frequent home nocturnal hemodialysis ( FHNHD ) has been renewed ; however , the cost-effectiveness of this technique is unknown . We performed a cost-utility analysis of FHNHD compared with conventional hemodialysis ( CvHD ; 4 hours three times per week ) from a health payer perspective over a lifetime horizon using patient information from the Alberta NHD r and omized controlled trial . Costs , including training costs , were obtained using microcosting and administrative data ( CAN$2012 ) . We determined the incremental cost per quality -adjusted life year ( QALY ) gained . Robustness was assessed using scenario , sensitivity , and probabilistic sensitivity analyses . Compared with CvHD ( 61 % in-center , 14 % satellite , and 25 % home dialysis ) , FHNHD led to incremental cost savings ( -$6700 ) and an additional 0.38 QALYs . In sensitivity analyses , when the annual probability of technique failure with FHNHD increased from 7.6 % ( reference case ) to ≥19 % , FHNHD became unattractive ( > $ 75,000/QALY ) . The cost/QALY gained became $ 13,000 if average training time for FHNHD increased from 3.7 to 6 weeks . In scenarios with alternate comparator modalities , FHNHD remained dominant compared with in-center CvHD ; cost/QALYs gained were $ 18,500 , $ 198,000 , and $ 423,000 compared with satellite CvHD , home CvHD , and peritoneal dialysis , respectively . In summary , FHNHD is attractive compared with in-center CvHD in this cohort . However , the attractiveness of FHNHD varies by technique failure rate , training time , and dialysis modalities from which patients are drawn , and these variables should be considered when establishing FHNHD programs BACKGROUND In this r and omized clinical trial , we aim ed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass , self-reported physical health , and other intermediate outcomes among patients undergoing maintenance hemodialysis . METHODS Patients were r and omly assigned to undergo hemodialysis six times per week ( frequent hemodialysis , 125 patients ) or three times per week ( conventional hemodialysis , 120 patients ) for 12 months . The two co primary composite outcomes were death or change ( from baseline to 12 months ) in left ventricular mass , as assessed by cardiac magnetic resonance imaging , and death or change in the physical-health composite score of the R AND 36-item health survey . Secondary outcomes included cognitive performance ; self-reported depression ; laboratory markers of nutrition , mineral metabolism , and anemia ; blood pressure ; and rates of hospitalization and of interventions related to vascular access . RESULTS Patients in the frequent-hemodialysis group averaged 5.2 sessions per week ; the weekly st and ard Kt/V(urea ) ( the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea ) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group ( 3.54±0.56 vs. 2.49±0.27 ) . Frequent hemodialysis was associated with significant benefits with respect to both co primary composite outcomes ( hazard ratio for death or increase in left ventricular mass , 0.61 ; 95 % confidence interval [ CI ] , 0.46 to 0.82 ; hazard ratio for death or a decrease in the physical-health composite score , 0.70 ; 95 % CI , 0.53 to 0.92 ) . Patients r and omly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis ( hazard ratio , 1.71 ; 95 % CI , 1.08 to 2.73 ) . Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia . There were no significant effects of frequent hemodialysis on cognitive performance , self-reported depression , serum albumin concentration , or use of erythropoiesis-stimulating agents . CONCLUSIONS Frequent hemodialysis , as compared with conventional hemodialysis , was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00264758 . ) Background Left ventricular ( LV ) hypertrophy is common among patients on hemodialysis . While a relationship between blood pressure ( BP ) and LV hypertrophy has been established , it is unclear which BP measurement method is the strongest correlate of LV hypertrophy . We sought to determine agreement between various blood pressure measurement methods , as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis . Methods This was a post-hoc analysis of data from a r and omized controlled trial . We evaluated the agreement between seven BP measurement methods : st and ardized measurement at baseline ; single pre- and post-dialysis , as well as mean intra-dialytic measurement at baseline ; and cumulative pre- , intra- and post-dialysis readings ( an average of 12 monthly readings based on a single day per month ) . Agreement was assessed using Lin 's concordance correlation coefficient ( CCC ) and the Bl and Altman method . Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve ( AUC ) . Results Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably , from a CCC of 0.35 to 0.94 , with overlapping 95 % confidence intervals . Pre-dialysis measurements were the weakest predictors of LV hypertrophy while st and ardized , post- and inter-dialytic measurements had similar and strong ( AUC 0.79 to 0.80 ) predictive power for LV hypertrophy . Conclusions A single st and ardized BP has strong predictive power for LV hypertrophy and performs just as well as more re source intensive cumulative measurements , whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy . Current guidelines , which recommend using pre-dialysis measurements , should be revisited to confirm these results CONTEXT Morbidity and mortality rates in hemodialysis patients remain excessive . Alterations in the delivery of dialysis may lead to improved patient outcomes . OBJECTIVE To compare the effects of frequent nocturnal hemodialysis vs conventional hemodialysis on change in left ventricular mass and health-related quality of life over 6 months . DESIGN , SETTING , AND PARTICIPANTS A 2-group , parallel , r and omized controlled trial conducted at 2 Canadian university centers between August 2004 and December 2006 . A total of 52 patients undergoing hemodialysis were recruited . INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive nocturnal hemodialysis 6 times weekly or conventional hemodialysis 3 times weekly . MAIN OUTCOME MEASURES The primary outcome was change in left ventricular mass , as measured by cardiovascular magnetic resonance imaging . The secondary outcomes were patient-reported quality of life , blood pressure , mineral metabolism , and use of medications . RESULTS Frequent nocturnal hemodialysis significantly improved the primary outcome ( mean left ventricular mass difference between groups , 15.3 g , 95 % confidence interval [ CI ] , 1.0 to 29.6 g ; P = .04 ) . Frequent nocturnal hemodialysis did not significantly improve quality of life ( difference of change in EuroQol 5-D index from baseline , 0.05 ; 95 % CI , -0.07 to 0.17 ; P = .43 ) . However , frequent nocturnal hemodialysis was associated with clinical ly and statistically significant improvements in selected kidney-specific domains of quality of life ( P = .01 for effects of kidney disease and P = .02 for burden of kidney disease ) . Frequent nocturnal hemodialysis was also associated with improvements in systolic blood pressure ( P = .01 after adjustment ) and mineral metabolism , including a reduction in or discontinuation of antihypertensive medications ( 16/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional hemodialysis group ; P < .001 ) and oral phosphate binders ( 19/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional dialysis group ; P < .001 ) . No benefit in anemia management was seen with nocturnal hemodialysis . CONCLUSION This preliminary study revealed that , compared with conventional hemodialysis ( 3 times weekly ) , frequent nocturnal hemodialysis improved left ventricular mass , reduced the need for blood pressure medications , improved some measures of mineral metabolism , and improved selected measures of quality of life . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N25858715 BACKGROUND The annual mortality rate for maintenance hemodialysis patients in the United States is unacceptably high at 15%-20 % . In 2004 , we initiated the Frequent Hemodialysis Network ( FHN ) clinical trials . This report presents baseline characteristics of FHN Trial participants and compares them with hemodialysis patients tracked in US Renal Data System ( USRDS ) data . STUDY DESIGN 2 separate r and omized clinical trials . SETTING S & PARTICIPANTS FHN includes 332 patients with chronic kidney disease requiring long-term dialysis therapy enrolled in 2 separate r and omized clinical trials . The FHN Daily Trial ( 245 r and omly assigned participants ) was design ed to compare outcomes of 6-times-weekly in-center daily hemodialysis ( 1.5 - 2.75 h/session ) with conventional 3-times-weekly in-center hemodialysis . The FHN Nocturnal Trial ( 87 r and omly assigned participants ) was design ed to compare outcomes of 6-times-weekly home nocturnal ( 6 - 8 h/session ) with conventional 3-times-weekly hemodialysis . USRDS data include 338,109 incident and prevalent long-term hemodialysis patients from the calendar year 2007 . RESULTS Participants in both trials were on average younger than the average hemodialysis patient in the United States ( Daily Trial , 50.4 years ; P < 0.001 ; Nocturnal Trial , 52.8 years ; P < 0.001 ) . Compared with USRDS data , whites were under-represented in the Daily Trial ( 36 % vs 55 % ; P < 0.001 ) , whereas Hispanics were under-represented in the Nocturnal Trial and over-represented in the Daily Trial ( 0 % vs 28 % ; P < 0.001 ) . In addition , there were more fistulas and fewer catheters in the Daily Trial ( 61 % and 20 % , respectively ; P < 0.001 for both ) and fewer grafts and more catheters in the Nocturnal Trial ( 10 % and 44 % , respectively ; P < 0.005 for both ) . LIMITATIONS Clinical trial exclusion criteria and patient willingness to participate limit comparisons with the USRDS . CONCLUSIONS FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population . Catheters for vascular access were more common in FHN Nocturnal Trial participants We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial . We compared changes in albumin , body weight and composition among 245 patients r and omized to 6- or 3-times per week in-center hemodialysis ( Daily Trial ) and 87 patients r and omized to 6-times per week nocturnal or 3-times per week conventional hemodialysis , performed largely at home ( Nocturnal Trial ) . In the Daily Trial , there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months . There was a significant relative decrease in pre-dialysis body weight of 1.5 ± 0.2 kg in the 6 times per week group at one month , but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months . Extracellular water decreased in the 6 times per week compared to the 3 per week hemodialysis group . There were no significant between-group differences in phase angle , intracellular water or body cell mass . In the Nocturnal Trial , there were no significant between-group differences in any study parameter . Any gain in “ dry ” body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant . Thus , frequent in-center hemodialysis reduced extracellular water but did not increase serum albumin or body cell mass while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition Background — An increase in left ventricular mass ( LVM ) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease . Methods and Results — The Frequent Hemodialysis Network ( FHN ) Daily Trial r and omized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis ; the FHN Nocturnal Trial r and omized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis . The main cardiac secondary outcome was change in LVM . In each trial , we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal , blood pressure , or solute clearance influenced the effect of frequent hemodialysis on LVM . In the Daily Trial , frequent hemodialysis result ed in a significant reduction in LVM ( 13.1 g ; 95 % CI , 5.0–21.3 g ; P=0.002 ) , LVM index ( 6.9 g/m2 ; 95 % CI , 2.4–11.3 g/m2 ; P=0.003 ) , and percent change in geometric mean of LVM ( 7.0 % ; 95 % CI , 1.0%–12.6 ; P=0.02 ) . Similar trends were noted in the Nocturnal Trial but did not reach statistical significance . In the Daily Trial , a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline . Changes in LVM were associated with changes in blood pressure ( conventional hemodialysis : R=0.28 , P=0.01 , daily hemodialysis : R=0.54 , P<0.001 ) and were not significantly associated with changes in other parameters . Conclusions — Frequent in-center hemodialysis reduces LVM . The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00264758 We measured mortality and morbidity among 114 patients assigned r and omly to home hemodialysis ( HD ) and home intermittent peritoneal dialysis ( IPD ) . Data were collected during the time of home training and for 12 months after initiation of home dialysis . Training time was shorter for the IPD than for the HD patients ( P less than 0.001 ) with median time 1.8 months for IPD and 3.9 months for HD . Switching to the alternative mode of treatment was more frequent for the IPD group ( 29/59 vs. 5/55 , P less than 0.001 ) . Survival time was not different , perhaps because of the modality change . More IPD patients were hospitalized in the first 6 months ( 20 for IPD vs. 9 for HD , P = 0.02 ) , but they had fewer troublesome cardiovascular events in the first year ( 0 vs. 12 , P less than 0.001 ) . The HD patients maintained better nutritional status as reflected in body weight and arm muscle circumference and possibly in urea appearance rate . Thus , these data suggest that for most patients , IPD is a less satisfactory form of therapy than HD , but certain advantages of IPD did emerge . Applications of this information to the currently more popular mode of CAPD await further study Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments . To study this further , we r and omized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week , all with single-use high-flux dialyzers . The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea ) , a 1.74-fold higher average number of treatments per week , and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm . We did not find a significant effect of nocturnal hemodialysis for either of the two co primary outcomes ( death or left ventricular mass ( measured by MRI ) with a hazard ratio of 0.68 , or of death or R AND Physical Health Composite with a hazard ratio of 0.91 ) . Possible explanations for the left ventricular mass result include limited sample size and patient characteristics . Secondary outcomes included cognitive performance , self-reported depression , laboratory markers of nutrition , mineral metabolism and anemia , blood pressure and rates of hospitalization , and vascular access interventions . Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension , but no significant benefit among the other main secondary outcomes . There was a trend for increased vascular access events in the nocturnal arm . Thus , we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either co primary outcome Objective To assess employment status in new end-stage renal disease ( ESRD ) patients at the start of dialysis and after 1 year , and to determine whether demographic and clinical variables and physical and psychosocial functioning at the start of dialysis are risk factors for loss of employment after 1 year of dialysis . Design Prospect i ve follow-up study in which 38 of 48 Dutch dialysis centers participate . Patients 659 patients who had started on dialysis and who were between 18 and 65 years old were included . Patients were re-examined after 12 months . Main Outcome Measures Demographic data , physical and psychosocial functioning with the Short-Form Health Survey ( SF-36 ) , and data on employment status were obtained using question naires . Nephrologists provided the clinical data . Results At the start of dialysis , 35 % of patients were employed , in contrast to 61 % of the general Dutch population . Within 1 year , the proportion of employed patients decreased from 31 % to 25 % of hemodialysis patients , and from 48 % to 40 % of peritoneal dialysis patients . In patients who were working at the start of dialysis , independent risk factors for loss of work within 1 year were impaired physical and psychosocial functioning [ odds ratio physical : 3.4 , 95 % confidence interval ( % CI ) , 1.0 – 11.2 ; odds ratio psychosocial : 4.2 , 95 % CI , 1.2 – 14.2 ] . Conclusions As the percentage of employed patients at the start of dialysis is about half the expected percent-age , loss of work is an important issue in both predialysis and dialysis patients . Improvements in physical and psychosocial functioning are potentially preventive of loss of work in patients who are employed when they start dialysis Observational studies suggest improvements with frequent hemodialysis ( HD ) , but its true efficacy and safety remain uncertain . The Frequent Hemodialysis Network Trials Group is conducting two multicenter r and omized trials of 250 subjects each , comparing conventional three times weekly HD with ( 1 ) in-center daily HD and ( 2 ) home nocturnal HD . Daily HD will be delivered for 1.5 - 2.75 h , 6 days/week , with target eK(t)/V(n ) > or = 0.9/session , whereas nocturnal HD will be delivered for > or = 6 h , 6 nights/week , with target stdK(t)/V of > or = 4.0/week . Subjects will be followed for 1 year . The composite of mortality with the 12-month change in ( i ) left ventricular mass index ( LVMI ) by magnetic resonance imaging , and ( ii ) SF-36 R AND Physical Health Composite ( PHC ) are specified as co- primary outcomes . The seven main secondary outcomes are between group comparisons of : change in LVMI , change in PHC , change in Beck Depression Inventory score , change in Trail Making Test B score , change in pre-HD serum albumin , change in pre-HD serum phosphorus , and rates of non-access hospitalization or death . Changes in blood pressure and erythropoiesis will also be assessed . Safety outcomes will focus on vascular access complications and burden of treatment . Data will be obtained on the cost of delivering frequent HD compared to conventional HD . Efforts will be made to reduce bias , including blinding assessment of subjective outcomes . Because no large-scale r and omized trials of frequent HD have been previously conducted , the first year has been design ated a Vanguard Phase , during which feasibility of r and omization , ability to deliver the interventions , and adherence will be evaluated BACKGROUND R and omized , controlled comparisons between home haemodialysis ( HHD ) and centre haemodialysis ( CHD ) have not been performed to date . Reported survival benefits of HHD as compared with CHD from uncontrolled studies have been attributed largely to patient selection . METHODS In order to minimize a selection bias , we have compared the outcome of our HHD and CHD patients with a nested case-cohort study . For each patient trained for HHD at our dialysis centre between 1970 and 1995 ( n=103 ) , a corresponding match was search ed from the CHD patients by retrospective chart analysis . The pairs were matched for sex , age ( + /-5 years ) , time of dialysis therapy onset ( + /-2 years ) and renal disease category . For 58 of the 103 HHD patients , a corresponding matched CHD patient was identified . Both treatment groups had the same mean age ( 50+/-13 years ) at dialysis onset and were comparable with respect to the Khan comorbidity index , prevalence and duration of hypertension , smoking habits , history of myocardial infa rct ion , stroke and peripheral vascular disease . In both groups , approximately 50 % of the patients were transplanted during the observation period . RESULTS HHD patients were hospitalized less often and tended to have fewer operations as compared with CHD patients . Survival was significantly longer in HHD as compared with CHD . Five , 10 and 20 year survival rates were 93 ( n=55 patients at risk ) , 72 ( 41 ) and 34 % ( 11 ) with HHD and 64 ( 38 ) , 48 ( 26 ) and 23 % ( 4 ) with CHD , respectively . This survival difference persisted after adjusting for predictors of mortality , i.e. age at onset of dialysis , year of start of dialysis therapy and Khan comorbidity index . CONCLUSIONS HHD offers a cheap and valuable alternative to CHD , with no apparent disadvantages Background Sexual dysfunction is common in patients with end stage renal disease ( ESRD ) and treatment options are limited . Observational studies suggest that nocturnal hemodialysis may improve sexual function . We compared sexual activity and responses to sexual related questions in the Kidney Disease Quality of Life Short Form question naire among patients r and omized to frequent nocturnal or thrice weekly conventional hemodialysis . Methods We performed a secondary analysis of data from an RCT which enrolled 51 patients comparing frequent nocturnal and conventional thrice weekly hemodialysis . Sexual activity and responses to sexual related questions were assessed at baseline and six months using relevant questions from the Kidney Disease Quality of Life Short Form question naire . Results Overall , there was no difference in sexual activity , or the extent to which people were bothered by the impact of kidney disease on their sex life between the two groups between r and omization and 6 months . However , women and patients age < 60 who were r and omized to frequent nocturnal hemodialysis were less bothered by the impact of kidney disease on their sex life at 6 months , compared with patients allocated to conventional hemodialysis ( p = 0.005 and p = 0.024 respectively ) . Conclusions Our results suggest that frequent nocturnal hemodialysis is not associated with an improvement in sexual activity in all patients but might have an effect on the burden of kidney disease on sex life in women and patients less than 60 years of age . The validity of these subgroup findings require confirmation in future RCTs Background Nocturnal hemodialysis ( NHD ) is an alternative to conventional three times per week hemodialysis ( CvHD ) and has been reported to improve several health outcomes . To date , no r and omized controlled trial ( RCT ) has compared NHD and CvHD . We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular ( LV ) mass , as measured by cardiac magnetic resonance imaging ( cMR ) . Methodology / design All patients in Alberta , Canada , expressing an interest in performing NHD are eligible for the study . Patients enrolled in the study will be r and omized to either NHD or CvHD for a six month period . All patients will have a full clinical assessment , including collection of biochemical and cMR data at baseline and at 6 months . Both groups of patients will be monitored biweekly to optimize blood pressure ( BP ) to a goal of < 130/80 mmHg post-dialysis using a predefined BP management protocol . The primary outcome is change in LV mass , a surrogate marker for cardiac mortality , measured at baseline and 6 months . The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography . Secondary outcomes include BP control , anemia , mineral metabolism , health-related quality of life , and costs . Discussion To our knowledge , this study will be the first RCT evaluating health outcomes in NHD . The impact of NHD on LV mass represents a clinical ly important outcome which will further eluci date the potential benefits of NHD and guide future clinical endpoint studies BACKGROUND End-stage renal disease is associated with reduced heart rate variability ( HRV ) , components of which generally are associated with advanced age , diabetes mellitus and left ventricular hypertrophy . We hypothesized that daily in-center hemodialysis ( HD ) would increase HRV . METHODS The Frequent Hemodialysis Network ( FHN ) Daily Trial r and omized 245 patients to receive 12 months of six versus three times per week in-center HD . Two hundred and seven patients had baseline Holter recordings . HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power ( LF , a measure of sympathetic modulation ) , high-frequency power ( HF , a measure of parasympathetic modulation ) and st and ard deviation ( SD ) of the R-R interval ( SDNN , a measure of beat-to-beat variation ) . RESULTS Baseline to Month 12 change in LF was augmented by 50 % [ 95 % confidence interval ( 95 % CI ) 6.1 - 112 % , P = 0.022 ] and LF + HF was augmented by 40 % ( 95 % CI 3.3 - 88.4 % , P = 0.03 ) in patients assigned to daily hemodialysis ( DHD ) compared with conventional HD . Changes in HF and SDNN were similar between the r and omized groups . The effects of DHD on LF were attenuated by advanced age and diabetes mellitus ( predefined subgroups ) . Changes in HF ( r = -0.20 , P = 0.02 ) and SDNN ( r = -0.18 , P = 0.04 ) were inversely associated with changes in left ventricular mass ( LVM ) . CONCLUSIONS DHD increased the LF component of HRV . Reduction of LVM by DHD was associated with increased vagal modulation of heart rate ( HF ) and with increased beat-to-beat heart rate variation ( SDNN ) , suggesting an important functional correlate to the structural effects of DHD on the heart in uremia We sought to determine whether lower mortality rates reported with hemodialysis ( HD ) at home compared to hemodialysis in dialysis centers ( center HD ) could be explained by patient selection . Data are from the United States Renal Data System ( USRDS ) Special Study Of Case Mix Severity , a r and om national sample of 4,892 patients who started renal replacement therapy in 1986 to 1987 . Intent-to-treat analyses compared mortality between home HD ( N = 70 ) and center HD patients ( N = 3,102 ) using the Cox proportional hazards model . Home HD patients were younger and had a lower frequency of comorbid conditions . The unadjusted relative risk ( RR ) of death for home HD patients compared to center HD was 0.37 ( P < 0.001 ) . The RR adjusted for age , sex , race and diabetes , was 44 % lower in home HD patients ( RR = 0.56 , P = 0.02 ) . When additionally adjusted for comorbid conditions , this RR increased marginally ( RR = 0.58 , P = 0.03 ) . A different analysis using national USRDS data from 1986/7 and without comorbid adjustment showed patients with training for self care hemodialysis at home or in a center ( N = 418 ) had a lower mortality risk ( RR = 0.78 , P = 0.001 ) than center HD patients ( N = 43,122 ) . Statistical adjustment for comorbid conditions in addition to age , sex , race , and diabetes explains only a small amount of the lower mortality with home HD BACKGROUND AND OBJECTIVES Patients receiving hemodialysis often perceive their caregivers are overburdened . We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In two separate trials , 245 patients were r and omized to receive in-center daily hemodialysis ( 6 days/week ) or conventional hemodialysis ( 3 days/week ) while 87 patients were r and omized to receive home nocturnal hemodialysis ( 6 nights/week ) or home conventional hemodialysis for 12 months . Changes in overall mean scores over time in the 10- question Cousineau perceived burden scale were compared . RESULTS In total , 173 of 245 ( 70 % ) and 80 of 87 ( 92 % ) r and omized patients in the Daily and Nocturnal Trials , respectively , reported having an unpaid caregiver at baseline or during follow-up . Relative to in-center conventional dialysis , the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 ( 95 % confidence interval , -9.4 to + 5.3 ; P=0.58 ) . Relative to home conventional dialysis , the 12-month change in mean perceived burden score with home nocturnal dialysis was + 6.1 ( 95 % confidence interval , -0.8 to + 13.1 ; P=0.08 ) . After multiple imputation for missing data in the Nocturnal Trial , the relative difference between home nocturnal and home conventional hemodialysis was + 9.4 ( 95 % confidence interval , + 0.55 to + 18.3 ; P=0.04 ) . In the Nocturnal Trial , changes in perceived burden were inversely correlated with adherence to dialysis treatments ( Pearson r=-0.35 ; P=0.02 ) . CONCLUSION Relative to conventional hemodialysis , in-center daily hemodialysis did not result in higher perceptions of caregiver burden . There was a trend to higher perceived caregiver burden among patients r and omized to home nocturnal hemodialysis . These findings may have implication s for the adoption of and adherence to frequent nocturnal hemodialysis We conducted a r and omized controlled trial to compare the quality of life of 52 patients undergoing nocturnal hemodialysis and conventional hemodialysis . Quality of life was measured using a number of established methods including the Kidney Disease Quality of Life Short Form and the preference-based Euroqol EQ-5D question naire ( whose scores varied from 0 to 1 ) . The primary outcome was a change in the Euroqol EQ-5D index scores between baseline and 6 months . We performed additional analyses comparing change in quality of life from pre-r and omization ( when patients were unaware of treatment allocation ) to 6 months . Other analyses considered the impact of nocturnal hemodialysis on four pre-selected Kidney Disease Quality of Life Short Form domains , and the longer term impact of nocturnal hemodialysis on quality of life . Compared with conventional hemodialysis , nocturnal hemodialysis increased Euroqol-EQ-5D index scores by 0.05 , which was not significantly different from baseline . When six-month values were compared with pre-r and omization values rather than baseline values , the between group difference was larger ( 0.12 ) though it was still not statistically significant ( P=.06 ) . Nocturnal hemodialysis was associated with clinical ly and statistically significant improvements in selected kidney-specific quality of life domains ( P=.01 for effects of kidney disease ; P=.02 for burden of kidney disease ) . Our primary quality of life analysis did not demonstrate a statistically significant change between nocturnal hemodialysis and conventional hemodialysis , though statistically significant and clinical ly important changes in some secondary kidney-disease- specific measures were observed OBJECTIVE More frequent dialysis may improve nutrition and remove dietary restrictions in hemodialysis ( HD ) patients . We present results from a trial comparing nutritional parameters between nocturnal hemodialysis ( NHD ) and conventional HD patients . METHODS Patients were r and omized to conventional thrice weekly HD or NHD for a 6-month study period . Dietary intake was recorded by patients using a 3-day food record at baseline and study exit . RESULTS Of 51 patients , 23 completed baseline and exit food records and were included in the analysis . Although dietary intake of calcium , potassium , and lipids increased in the NHD group , serum levels of calcium and potassium remained within target limits . The majority of NHD subjects were able to reduce or discontinue their phosphate binders and maintain serum phosphate levels within target limits . Serum albumin improved among the NHD group ( 0.7 g/L ) and declined for the conventional group ( -1.6 g/L ) . None of the between group differences achieved statistical significance . CONCLUSIONS As compared with conventional dialysis , NHD was associated with a nonstatistically significant increase in dietary intake for some nutrients , with maintenance of serum levels for potassium , calcium , and phosphorus . Whether increased dietary intake translates into improvement in morbidity and mortality remains to be determined The optimal combination of hemodialysis ( HD ) dose and session length remains uncertain , and previous studies have not conclusively shown session length to be an important independent determinant of patient mortality . The objective of this study was to examine associations between HD dose and session length with mortality risk using data from the Australian and New Zeal and Dialysis and Transplant Registry . Analyses were performed using a prospect i ve inception cohort comprising all incident adult patients treated by thrice-weekly maintenance HD , who commenced renal replacement therapy with HD between 1 April 1997 and 31 March 2004 . In all , 6593 patients were identified , of whom 4193 had sufficient data for multivariate analyses . HD dose ( single pool fractional clearance of urea , Kt/V ) and session length were included in analyses as those recorded 12 months after HD inception to reduce confounding by residual renal function . The outcome examined was patient mortality . Survival analyses included Kaplan-Meier calculations of survival and Cox regression for multivariate analyses . Covariates in Cox models included patient demographics , co-morbid medical conditions at HD inception , and HD operating parameters . After adjustment for covariates and each other , Kt/V of 1.30 - 1.39 and session length of 4.5 - 4.9 h were associated with the lowest mortality risk . There was no interaction between HD dose and session length . Thus , the optimal combination for mortality appears to be Kt/V of > or = 1.3 and session length of > or = 4.5 h. These data suggest a r and omized controlled trial to test these hypotheses , and support the inclusion of criteria relating to session length in definitions of adequate HD practice BACKGROUND AND OBJECTIVES Higher left ventricular volume is associated with death in patients with ESRD . This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The Frequent Hemodialysis Network daily trial r and omized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis ; the Frequent Hemodialysis Network nocturnal trial r and omized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis . Left and right ventricular end systolic and diastolic volumes , left ventricular mass , and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging . The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling . In each trial , the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups . RESULTS In the daily trial , frequent hemodialysis result ed in significant reductions in left ventricular end diastolic volume ( -11.0 % [ 95 % confidence interval , -16.1 % to -5.5 % ] ) , left ventricular end systolic volume ( -14.8 % [ -22.7 % to -6.2 % ] ) , right ventricular end diastolic volume ( -11.6 % [ -19.0 % to -3.6 % ] ) , and a trend for right ventricular end systolic volume ( -11.3 % [ -21.4 % to 0.1 % ] ) compared with conventional therapy . The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d ( P value [interaction]=0.02 ) . In the nocturnal trial , there were no significant changes in left or right ventricular volumes . The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial . CONCLUSIONS Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass , but it does not affect left ventricular remodeling Longer treatment time ( TT ) and slower ultrafiltration rate ( UFR ) are considered advantageous for hemodialysis ( HD ) patients . The study included 22,000 HD patients from seven countries in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) . Logistic regression was used to study predictors of TT > 240 min and UFR > 10 ml/h/kg bodyweight . Cox regression was used for survival analyses . Statistical adjustments were made for patient demographics , comorbidities , dose of dialysis ( Kt/V ) , and body size . Europe and Japan had significantly longer ( P < 0.0001 ) average TT than the US ( 232 and 244 min vs 211 in DOPPS I ; 235 and 240 min vs 221 in DOPPS II ) . Kt/V increased concomitantly with TT in all three regions with the largest absolute difference observed in Japan . TT > 240 min was independently associated with significantly lower relative risk ( RR ) of mortality ( RR = 0.81 ; P = 0.0005 ) . Every 30 min longer on HD was associated with a 7 % lower RR of mortality ( RR = 0.93 ; P < 0.0001 ) . The RR reduction with longer TT was greatest in Japan . A synergistic interaction occurred between Kt/V and TT ( P = 0.007 ) toward mortality reduction . UFR > 10 ml/h/kg was associated with higher odds of intradialytic hypotension ( odds ratio = 1.30 ; P = 0.045 ) and a higher risk of mortality ( RR = 1.09 ; P = 0.02 ) . Longer TT and higher Kt/V were independently as well as synergistically associated with lower mortality . Rapid UFR during HD was also associated with higher mortality risk . These results warrant a r and omized clinical trial of longer dialysis sessions in thrice-weekly HD BACKGROUND The Frequent Hemodialysis Network ( FHN ) is conducting 2 r and omized clinical trials , a daytime in-center trial ( " daily " ) comparing 6 versus 3 treatments/wk , and a home nocturnal trial comparing 6 nocturnal treatments versus 3 conventional treatments/wk . The goal of this study was to project separation between the treatment and control arms of these studies for measures of dialysis dose by using simulations based on 2-compartment variable-volume models . SETTING & PARTICIPANTS Data from the most recent hemodialysis treatment in 100 patients dialyzed 3 times/wk at facilities of the Renal Research Institute in New York and from 2 data sets ( n = 154 and 115 patients ) from the Hemodialysis ( HEMO ) trial . DESIGN Observational study . PREDICTOR Dialysis prescriptions for the treatment and control arms in the FHN trials . DIALYSIS REGIMEN OUTCOMES : Treatment time , ultrafiltration rate , st and ard Kt/V/wk for urea ( stdKt/V(urea ) ) , and continuous clearance estimates based on ratios of urea , creatinine , and normalized beta(2)-microglobulin generation rates ( denoted by Gn ) to time-averaged concentrations ( TACs ) of these solutes during 1 treatment week . RESULTS The expected differences between median values in the experimental and control groups were weekly treatment time : daily trial , 29 % ; nocturnal trial , 234 % ; ultrafiltration rate : daily , -20 % ; nocturnal , -69 % ; stdKt/V(urea ) : daily , 52 % ; nocturnal , 133 % ; Gn(urea)/TAC(urea ) : daily , 34 % ; nocturnal , 130 % ; Gn(cr)/TAC(cr ) : daily , 31 % ; nocturnal , 135 % ; and Gn(beta2)/TAC(beta2 ) : daily , 8 % ; nocturnal , 67 % . LIMITATIONS Use of simulated data and assumption of equivalent volumes and ultrafiltration rates between treatment arms . CONCLUSIONS The nocturnal 6-times-weekly regimen produces substantially greater separation between the treatment and control arms than the daytime 6-times-weekly regimen for a wide range of treatment parameters . However , the 6-times-weekly interventions in both FHN trials will produce substantially greater separation than in the HEMO trial , where separations in median weekly treatment time and stdKt/V(urea ) between the 3-times-weekly high- and st and ard-dose groups were 18 % and 17 % , respectively . The FHN trials will test whether substantial increases in solute clearance and other effects of frequent hemodialysis material ly influence selected intermediate outcome measures Frequent hemodialysis requires using the vascular access more often than with conventional hemodialysis , but whether this increases the risk for access-related complications is unknown . In two separate trials , we r and omly assigned 245 patients to receive in-center daily hemodialysis ( 6 days per week ) or conventional hemodialysis ( 3 days per week ) and 87 patients to receive home nocturnal hemodialysis ( 6 nights per week ) or conventional hemodialysis , for 12 months . The primary vascular access outcome was time to first access event ( repair , loss , or access-related hospitalization ) . Secondary outcomes were time to all repairs and time to all losses . In the Daily Trial , 77 ( 31 % ) of 245 patients had a primary outcome event : 33 repairs and 15 losses in the daily group and 17 repairs , 11 losses , and 1 hospitalization in the conventional group . Overall , the risk for a first access event was 76 % higher with daily hemodialysis than with conventional hemodialysis ( hazard ratio [ HR ] , 1.76 ; 95 % confidence interval [ CI ] , 1.11 - 2.79 ; P=0.017 ) ; among the 198 patients with an arteriovenous ( AV ) access at r and omization , the risk was 90 % higher with daily hemodialysis ( HR , 1.90 ; 95 % CI , 1.11 - 3.25 ; P=0.02 ) . Daily hemodialysis patients had significantly more total AV access repairs than conventional hemodialysis patients ( P=0.011 ) , with 55 % of all repairs involving thrombectomy or surgical revision . Losses of AV access did not differ between groups ( P=0.58 ) . We observed similar trends in the Nocturnal Trial , although the results were not statistically significant . In conclusion , frequent hemodialysis increases the risk of vascular access complications . The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance Several retrospective and uncontrolled prospect i ve studies reported blood pressure ( BP ) normalization and left ventricular mass ( LVM ) reduction during daily hemodialysis ( DHD ) . Conversely , the burden of these major independent risk factors is only marginally reduced by the initiation of st and ard thrice-weekly dialysis ( SHD ) , and cardiovascular events still represent the most common cause of death in hemodialysis patients . Therefore , we performed a r and omized two-period crossover study to compare the effect of short DHD versus SHD on BP and LVM in hypertensive patients with end-stage renal disease . We studied 12 hypertensive patients who had been stable on SHD treatment for more than 6 months . At the end of 6 months of SHD and 6 months of DHD in a sequence of r and omly assigned 24-hour ambulatory BP monitoring , echocardiography and bioimpedance were performed . Throughout the study , patients maintained the same Kt/V. A significant reduction in 24-hour BP during DHD was reported ( systolic BP [ SBP ] : DHD , 128 + /- 11.6 mm Hg ; SHD , 148 + /- 19.2 mm Hg ; P < 0.01 ; diastolic BP : DHD , 67 + /- 8.3 mm Hg ; SHD , 73 + /- 5.4 mm Hg ; P = 0.01 ) . The decrease in BP was accompanied by the withdrawal of antihypertensive therapy in 7 of 8 patients during DHD ( P < 0.01 ) . LVM index ( LVMI ) decreased significantly during DHD ( DHD , 120.1 + /- 60.4 g/m(2 ) ; SHD , 148.7 + /- 59.7 g/m(2 ) ; P = 0.01 ) . Extracellular water ( ECW ) content decreased from 52.7 % + /- 11.4 % to 47.6 % + /- 7.5 % ( P = 0.02 ) and correlated with 24-hour SBP ( r = 0.63 ; P < 0.01 ) and LVMI ( r = 0.66 ; P < 0.01 ) . In conclusion , this prospect i ve crossover study confirms that DHD allows optimal control of BP , reduction in LVMI , and withdrawal of antihypertensive treatment . These effects seem to be related to reduction in ECW content BACKGROUND Cognitive impairment is common in patients with end-stage renal disease receiving hemodialysis 3 times per week . STUDY DESIGN R and omized clinical trial . SETTING & PARTICIPANTS 218 individuals participating in the Frequent Hemodialysis Network ( FHN ) Daily Trial and 81 participating in the FHN Nocturnal Trial . INTERVENTION The Daily Trial tested in-center hemodialysis 6 times per week versus 3 times per week . The Nocturnal Trial tested home nocturnal hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per week . OUTCOMES Cognitive function was measured at baseline , month 4 , and month 12 . The primary outcome was performance on the Trail-Making Test , Form B , a measure of executive function , and a secondary outcome was performance on the Modified Mini-Mental State Examination , a measure of global cognition . The domains of attention , psychomotor speed , memory , and verbal fluency were assessed in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial . RESULTS We found no benefit of frequent hemodialysis in either trial for the primary cognitive outcome ( Daily Trial : OR for improvement , 0.99 ; 95 % CI , 0.59 - 1.66 ; Nocturnal Trial : OR , 1.19 ; 95 % CI , 0.48 - 2.96 ) . Similarly , there was no benefit of frequent hemodialysis in either trial on global cognition , the secondary cognitive outcome . Exploratory analyses in the Daily Trial suggested possible benefits of frequent hemodialysis for memory and verbal fluency , but not for attention and psychomotor speed . Exploratory analyses in the Nocturnal Trial suggested no benefit of frequent hemodialysis on attention , psychomotor speed , memory , or verbal fluency . LIMITATIONS Unblinded intervention , small sample . CONCLUSIONS Frequent hemodialysis did not improve executive function or global cognition Decrease in the average duration of hemodialysis treatment time is a continuing phenomenon . We investigated the relationship of 3-year mortality to duration of dialysis in a 1984 - 1985 national r and om sample of 600 hemodialysis patients from 36 dialysis units . Mortality was negatively associated with duration of dialysis treatments , as shown by the Cox model , adjusted for other patient and dialysis unit covariates . With adjustment for other covariates , patients receiving an average dialysis treatment duration of less than 3.5 hours had relative mortality risks of 1.17 to 2.18 compared with those with treatments longer than 3.5 hours ( mortality risk of 1.0 ) . Reverse causation ( the possibility that more seriously ill patients received dialysis for a shorter time ) appears unlikely . We conclude that duration of the dialysis procedure is an important element in determining patient mortality as one of the factors determining the adequacy of dialysis We conducted a r and omized crossover trial to establish , within patients , whether long-slow hemodialysis ( HD ) was associated with better blood pressure ( BP ) control than st and ard HD . Nine home HD patients , not on antihypertensive drugs , were dialyzed to the same eKt/Vurea and target weights for 6–8 h ( LD ) at home and for 3.5–4.5 h ( SD ) in the dialysis center 3 times weekly in r and omized sequence , with each phase lasting 8 weeks . Ambulatory BP , bioimpedance , neurohormones and autonomic function were measured in each phase . Pre- and postdialysis systolic , ambulatory systolic and diastolic BP were all higher with SD than with LD and intradialysis hypotension was more common . Weight , ECF volume and neurohormones did not differ between treatments . Muscle sympathetic activity was increased in both phases and cardiac sympathetic activity tended higher during SD . These findings suggest that additional factors to ECF volume may contribute to the superior BP control produced by long-slow HD Home hemodialysis has been a therapeutic option for almost 4 decades . The complexity of dialysis equipment has been a factor‐limiting adoption of this modality . We performed a feasibility study to demonstrate the safety of center‐based vs. home‐based daily hemodialysis with the NxStage System One portable hemodialysis device . We also performed a retrospective analysis to determine if clinical effects previously associated with short‐daily dialysis were also seen using this novel device . We conducted a prospect i ve , 2‐treatment , 2‐period , open‐label , crossover study of in‐center hemodialysis vs. home hemodialysis in 32 patients treated at 6 U.S. centers . The 8‐week In‐Center Phase ( 6 days/week ) was followed by a 2‐week transition period and then followed by the 8‐week Home Phase ( 6 days/week ) . We retrospectively collected data on hemodialysis treatment parameters immediately preceding the study in a subset of patients . Twenty‐six out of 32 patients ( 81 % ) successfully completed the study . Successful delivery of at least 90 % of prescribed fluid volume ( primary endpoint ) was achieved in 98.5 % of treatments in‐center and 97.3 % at home . Total effluent volume as a percentage of prescribed volume was between 94 % and 100 % for all study weeks . The composite rate of intradialytic and interdialytic adverse events per 100 treatments was significantly higher for the In‐Center Phase ( 5.30 ) compared with the Home Phase ( 2.10 ; p=0.007 ) . Compared with the period immediately preceding the study , there were reductions in blood pressure , antihypertensive medications , and interdialytic weight gain . Daily home hemodialysis with a small , easy‐to‐use hemodialysis device is a viable dialysis option for end‐stage renal disease patients capable of self/partner‐administered dialysis The average life expectancy of a person on hemodialysis is less than 3 years and has n't changed in 20 years . The Hemodialysis ( HEMO ) trial , a r and omized trial to determine whether increasing urea removal to the maximum practical degree through a 3-times-a-week schedule , showed no difference in mortality in the treatment and control groups . Investigators speculated that the increment in functional waste removal in the HEMO study was too small to produce improvements in mortality . To test this hypothesis , the NIDDK funded the Frequent Hemodialysis Network , a consortium of centers testing whether patients r and omized to intensive dialysis would demonstrate improved ( reduced ) left ventricular LV mass and quality of life . The trial has two arms : the daily ( in-center ) and the home ( nocturnal ) arms . Each arm has patients r and omized to conventional dialysis or 6 days ( or nights ) of dialysis . The results of the HEMO trial will be reported in the fall of 2010 The beneficial effect of correcting anemia in end stage renal failure using recombinant human erythropoietin ( rHuEPO ) is sometimes complicated by thrombosis of the arteriovenous fistula . This placebo-controlled study investigated the relationship between hemorheological changes caused by rHuEPO and alterations in fistula function and heparin requirements in home hemodialysis patients . Erythropoietin induced a rise in high shear rate blood viscosity , a determinant of blood flow in large vessels . Doppler assessment of brachial artery blood flows , tests of fistula function and heparin requirements were similar in the two patient groups . These findings indicate that rHuEPO treatment of renal anemia result ed in the expected rise in red blood cell mass and blood viscosity although these changes did not cause problems with arteriovenous access or alter fistula function in the short term BACKGROUND Patients undergoing maintenance hemodialysis frequently exhibit poor mental health . We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health . STUDY DESIGN 1-year r and omized controlled clinical trials . SETTING & PARTICIPANTS Hemodialysis centers in the United States and Canada . 332 patients were r and omly assigned to frequent ( 6-times-weekly ) compared with conventional ( 3-times-weekly ) hemodialysis in the Frequent Hemodialysis Network ( FHN ) Daily ( n = 245 ) and Nocturnal ( n = 87 ) Trials . INTERVENTION The Daily Trial was a trial of frequent ( 6-times-weekly ) compared with conventional ( 3-times-weekly ) in-center hemodialysis . The Nocturnal Trial assigned patients to either frequent nocturnal ( 6-times-weekly ) hemodialysis or conventional ( 3-times-weekly ) hemodialysis . OUTCOMES Self-reported depressive symptoms and mental health . MEASUREMENTS Beck Depression Inventory and the mental health composite score and emotional subscale of the R AND 36-Item Health Survey at baseline and 4 and 12 months . The mental health composite score is derived by summarizing these domains of the R AND 36-Item Health Survey : emotional , role emotional , energy/fatigue , and social functioning scales . RESULTS In the Daily Trial , participants r and omly assigned to frequent compared with conventional in-center hemodialysis showed no significant change over 12 months in adjusted mean Beck Depression Inventory score ( -1.9 ± 0.7 vs -0.6 ± 0.7 ; P = 0.2 ) , but experienced clinical ly significant improvements in adjusted mean mental health composite ( 3.7 ± 0.9 vs 0.2 ± 1.0 ; P = 0.007 ) and emotional subscale ( 5.2 ± 1.6 vs -0.3 ± 1.7 ; P = 0.01 ) scores . In the Nocturnal Trial , there were no significant changes in the same metrics in participants r and omly assigned to nocturnal compared with conventional hemodialysis . LIMITATIONS Trial interventions were not blinded . CONCLUSIONS Frequent in-center hemodialysis , as compared with conventional in-center hemodialysis , improved self-reported general mental health . Changes in self-reported depressive symptoms were not statistically significant . We were unable to conclude whether nocturnal hemodialysis yielded similar effects BACKGROUND AND OBJECTIVES Relatively little is known about the effects of hemodialysis frequency on the disability of patients with ESRD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This study examined changes in physical performance and self-reported physical health and functioning among subjects r and omized to frequent ( six times per week ) compared with conventional ( three times per week ) hemodialysis in both the Frequent Hemodialysis Network daily ( n=245 ) and nocturnal ( n=87 ) trials . The main outcome measures were adjusted change in scores over 12 months on the short physical performance battery ( SPPB ) , R AND 36-item health survey physical health composite ( PHC ) , and physical functioning subscale ( PF ) based on the intention to treat principle . RESULTS Overall scores for SPPB , PHC , and PF were poor relative to population norms and in line with other studies in ESRD . In the Daily Trial , subjects r and omized to frequent compared with conventional in-center hemodialysis experienced no significant change in SPPB ( adjusted mean change of -0.20±0.19 versus -0.41±0.21 , P=0.45 ) but experienced significant improvement in PHC ( 3.4±0.8 versus 0.4±0.8 , P=0.009 ) and a relatively large change in PF that did not reach statistical significance . In the Nocturnal Trial , there were no significant differences among subjects r and omized to frequent compared with conventional hemodialysis in SPPB ( adjusted mean change of -0.92±0.44 versus -0.41±0.43 , P=0.41 ) , PHC ( 2.7±1.4 versus 2.1±1.5 , P=0.75 ) , or PF ( -3.1±3.5 versus 1.1±3.6 , P=0.40 ) . CONCLUSIONS Frequent in-center hemodialysis compared with conventional in-center hemodialysis improved self-reported physical health and functioning but had no significant effect on objective physical performance . There were no significant effects of frequent nocturnal hemodialysis on the same physical metrics |
11,295 | 28,652,120 | Several new predictors of SDHC after aSAH were identified that may assist with the early recognition and prevention of SDHC .
The controversial evidence found in this study was insufficient to support the potential of neurosurgical clipping for reducing the risk of shunt dependency . | BACKGROUND Hydrocephalus is a well-recognized complication after aneurysmal subarachnoid hemorrhage ( aSAH ) .
This study aim ed to identify predictors for shunt-dependent hydrocephalus ( SDHC ) after aSAH via a systematic review and meta- analysis . | Subarachnoid hemorrhage ( SAH ) often leads to hydrocephalus , which is commonly treated by placement of a ventriculoperitoneal ( VP ) shunt . There is controversy over which factors affect the need for such treatment . In this study , data were prospect ively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center . External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus , and VP shunts were placed in patients with chronic hydrocephalus . The data were retrospectively analyzed using two- sample t-tests , Fisher 's exact test and logistic regression analysis . Overall , shunt dependency occurred in 91 of the 389 patients ( 23.4 % ) . Using logistic regression analysis , two factors were found to be significantly associated with VP shunt placement : an initial Glasgow Coma Scale ( GCS ) score of 8 - 14 ( 8 - 14 versus 3 - 7 , p = 0.016 ; 15 versus 3 - 7 , p = 0.55 ) ; and aneurysm coiling ( p = 0.017 ) . Patients with an initial GCS score of 8 - 14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3 - 7 . Those with a GCS of 15 had a 50 % lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8 - 14 . To clarify and strengthen these observations , prospect i ve , r and omized trials are needed OBJECTIVE Chronic hydrocephalus requiring shunt placement and cerebral vasospasm are common complications after aneurysmal subarachnoid hemorrhage . Recent publications have investigated the possibility that microsurgical fenestration of the lamina terminalis during aneurysm surgery may reduce the incidence of shunt-dependent hydrocephalus and cerebral vasospasm . We review ed a single-surgeon series to compare postsurgical outcomes of patients who underwent fenestration of the lamina terminalis against those who did not . METHODS This study is a retrospective review of the medical records of 369 consecutive patients with aneurysmal subarachnoid hemorrhage admitted to Columbia University Medical Center between January 2000 and July 2006 . All patients underwent craniotomy and clipping of at least one ruptured cerebral aneurysm by a single neurosurgeon ( ESC ) . The incidences of shunt-dependent hydrocephalus , conversion from acute hydrocephalus on admission to chronic hydrocephalus , and clinical cerebral vasospasm were compared in patients who underwent fenestration of the lamina terminalis with those who did not . The patient cohort was thus divided into three subgroups : 1 ) patients whose operative records clearly indicated that they underwent fenestration of the lamina terminalis , 2 ) patients whose operative records clearly indicated that they did not undergo fenestration of the lamina terminalis , and 3 ) patients whose operative records did not indicate one way or another whether they received fenestration of the lamina terminalis . We performed two separate analyses by comparing the postsurgical outcomes in those patients who were fenestrated versus those who were definitively not fenestrated and comparing the postsurgical outcomes in those patients who were fenestrated versus those who were not plus those whose records did not document fenestration . To further control for any cohort differences , we performed a comparison between patients who were fenestrated and those who were not after matching 1:1 for presenting radiographic and clinical characteristics predictive of hydrocephalus and vasospasm . Outcomes were compared using logistic regression and multivariable analysis . RESULTS In the first model , fenestrated patients had a shunt rate , conversion rate , and rate of clinical vasospasm of 25 , 50 , and 23 % , respectively , versus 20 , 27 , and 27 % in nonfenestrated patients , respectively ( P = 0.28 , 0.21 , and 0.32 , respectively ) . In the second model , the nonfenestrated patients plus nondocumented patients had a shunt rate , conversion rate , and rate of clinical vasospasm of 16 , 40 , and 20 % , respectively ( P = 0.19 , 0.33 , and 0.60 , respectively ) . In the matched cohort , fenestrated patients had a shunt rate , conversion rate , and rate of clinical vasospasm of 29 , 67 , and 20 % , respectively , versus 20 , 25 , and 25 % in nonfenestrated patients , respectively ( P = 0.30 , 0.24 , and 0.20 , respectively ) . CONCLUSION In contrast to other retrospective multisurgeon series , our retrospective single-surgeon series suggests that microsurgical fenestration of the lamina terminalis may not reduce the incidence of shunt-dependent hydrocephalus or cerebral vasospasm after aneurysmal subarachnoid hemorrhage . A prospect i ve multicenter trial is needed to definitively address the use of this maneuver BACKGROUND Shunt-dependent hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage ( aSAH ) . There is a need to identify patients who require ventriculoperitoneal shunt ( VPS ) insertion so that any modifiable risk factors can be addressed early after aSAH . METHODS Exploratory analysis was performed on 413 patients enrolled in CONSCIOUS-1 , a prospect i ve r and omized controlled trial of patients with aSAH treated with clazosentan . The association between clinical and neuroimaging covariates and VPS placement was first determined by univariate analysis . Covariates with P < 0.15 on univariate analysis were then analyzed in a multivariate logistic regression model . Receiver operating characteristic curve analysis was used to define optimal predictive thresholds . The published literature was review ed to determine the overall rate of VPS insertion after aSAH . RESULTS Overall , 17.2 % ( 71/413 ) of patients required VPS insertion . Multivariate analysis demonstrated that insertion of an external ventricular drain ( odds ratio , 6.21 ; 95 % confidence interval , 2.51 - 16.91 ) and increasing volume of cerebrospinal fluid ( CSF ) drainage per day ( odds ratio , 1.004 ; 95 % confidence interval , 1.000 - 1.009 ) were associated with VPS insertion . Receiver operating characteristic curve analysis revealed an optimal daily CSF output threshold of 78 mL was predictive of VPS insertion . Among 41,789 patients with aSAH from 66 published studies , the overall VPS insertion rate was 12.7 % . CONCLUSIONS The presence of an external ventricular drain and increased daily CSF output ( above 78 mL/day ) seems to be predictive of subsequent VPS insertion after aSAH . Although we could not identify modifiable risk factors for needing a VPS , nevertheless , these findings identify patients at greatest risk of VPS placement and inform treatment decisions as well as patient expectations OBJECTIVE The goals of this study were to investigate the risk factors , indications , complications , and outcome for patients with ventriculoperitoneal shunts ( VPSs ) after subarachnoid hemorrhage and to define a subgroup eligible for future prospect i ve studies design ed to clarify indications for placement of a VPS . METHODS Clinical characteristics of 236 prospect ively evaluated patients with subarachnoid hemorrhage and 6 months of follow-up were analyzed . Hydrocephalus was estimated by the relative bicau date index ( RBCI ) measured on computed tomographic scans at the time of shunting . Patients were divided into three groups by ventricle size : Group 1 included 121 patients with small ventricles ( RBCI < 1.0 ) , Group 2 included 88 patients with borderline ventricle size ( RBCI 1.0–1.4 ) , and Group 3 included 27 patients with markedly enlarged ventricles ( RBCI > 1.4 ) . RESULTS Initially , 86 patients ( 36 % ) underwent ventriculoperitoneal shunting : 19 in Group 1 ( 16 % ) , 43 in Group 2 ( 49 % ) , and 24 in Group 3 ( 90 % ) . Indications for placement of a VPS , risk factors , and outcome differed markedly by group . Four patients ( 3 % of those not initially shunted ) developed delayed hydrocephalus requiring a VPS , including one in Group 2 ( 2 % ) . The 6-month shunt complication rate was 13 % . Evaluation of patients in Group 2 indicated that functional status was an important factor in selecting c and i date s for shunting , and that patients receiving shunts and shunt-free patients demonstrated improvement in functional status during follow-up . CONCLUSION Although we currently use a proactive shunting paradigm for posthemorrhagic hydrocephalus , this report demonstrates that a conservative approach to patients with borderline ventricle size ( i.e. , RBCI of 1.0–1.4 ) and normal intracranial pressure should be evaluated in a prospect i ve r and omized trial Background Hydrocephalus ( HC ) after aneurysmal subarachnoid hemorrhage ( aSAH ) is a common sequel . Proper selection of patients in need of permanent cerebrospinal fluid ( CSF ) diversion is , however , not straightforward . The aim of this study was to identify predictors of CSF shunt dependency following aSAH . Methods We re-analyzed data acquired from aSAH patients previously enrolled in a prospect i ve , controlled single-center clinical trial in which shunt dependency was not one of the end points . In the present study patients were allocated into two groups : those receiving a shunt ( here denoted as shunt dependent ) and those not receiving a shunt , based on a clinical decision process . Predictors of shunt dependency were identified by applying uni- and multivariable analysis . We tested a set of predefined possible risk factors based on the results of the clinical trial , including the impact of CSF drainage volume exceeding 1,500 ml during the 1st week after ictus . Results Ninety patients were included in the study . Significant predictors of shunt dependency were poor clinical grade at admission [ odds ratio ( OR ) 4.7 , 95 % confidence interval ( CI ) 1.2–18.4 ] , large amounts of subarachnoid blood ( OR 3.8 , 95 % CI 1.0–14.0 ) , large ventricular size on preoperative cerebral computer tomographic ( CT ) scans ( OR 1.0 , 95 % CI 1.0–1.1 ) , and CSF volume drainage exceeding 1,500 ml during the 1st week after the ictus ( OR 16.3 , 95 % CI 4.0–67.1 ) . Age ≥70 years , larger amounts of intraventricular blood , vertebrobasilar aneurysm , and endovascular treatment tended to increase the likelihood of receiving a shunt . Outcome was not significantly different between shunted and non-shunted patients . Conclusions In this cohort of patients with clinical grade aSAH at admission , larger amounts of subarachnoid blood and large ventricular size on preoperative cerebral CT , and CSF drainage in excess of 1,500 ml during the 1st week after the ictus were significant predictors of shunt dependency . Shunt dependency did not hamper outcome BACKGROUND Acute hydrocephalus is a well-known sequela of aneurysmal subarachnoid hemorrhage ( SAH ) . Controversy exists about whether open microsurgical methods serve to reduce shunt dependency compared with endovascular techniques . OBJECTIVE To determine predictors of shunt-dependent hydrocephalus and functional outcomes after aneurysmal SAH . METHODS A total of 471 patients who were part of a prospect i ve , r and omized , controlled trial from 2003 to 2007 were retrospectively review ed . All variables including demographic data , medical history , treatment , imaging , and functional outcomes were included as part of the trial . No additional variables were retrospectively collected . RESULTS Ultimately , 147 patients ( 31.2 % ) required a ventriculoperitoneal shunt ( VPS ) in our series . Age , dissecting aneurysm type , ruptured vertebrobasilar aneurysm , Fisher grade , Hunt and Hess grade , admission intraventricular hemorrhage , admission intraparenchymal hemorrhage , blood in the fourth ventricle on admission , perioperative ventriculostomy , and hemicraniectomy were significant risk factors ( P < .05 ) associated with shunt-dependent hydrocephalus on univariate analysis . On multivariate analysis , intraventricular hemorrhage and intraparenchymal hemorrhage were independent risk factors for shunt dependency ( P < .05 ) . Clipping vs coiling treatment was not statistically associated with VPS after SAH on both univariate and multivariate analyses . Patients who did not receive a VPS at discharge had higher Glasgow Outcome Scale and Barthel Index scores and were more likely to be functionally independent and to return to work 72 months after surgery ( P < .05 ) . CONCLUSION There is no difference in shunt dependency after SAH among patients treated by endovascular or microsurgical means . Patients in whom shunt-dependent hydrocephalus does not develop after SAH tend to have improved long-term functional outcomes OBJECT This study was design ed to determine whether the frequency of shunt-dependent hydrocephalus in patients suffering from aneurysmal subarachnoid hemorrhage ( SAH ) differs when comparing surgical clip application with endovascular obliteration of ruptured aneurysms . METHODS In this prospect i ve nonr and omized study , 245 patients with aneurysmal SAH treated using either surgical clip application or endovascular coil embolization were studied at our institution between September 1997 and March 2003 . One hundred eighty patients underwent clip application and 65 had coil embolization . In those patients who underwent clip application of anterior circulation aneurysms , the lamina terminalis was systematic ally fenestrated . The occurrence of acute , asymptomatic , and shunt-dependent hydrocephalus was analyzed in both treatment groups . A subgroup analysis of patients with good clinical grade ( World Federation of Neurosurgical Societies [ WFNS ] Grade s I-III ) and better Fisher Grade ( 1 - 3 ) and of patients with Fisher Grade 4 hemorrhage was performed . Acute hydrocephalus was observed in 19 % of surgical cases and 46 % of endovascular ones . The occurrence of asymptomatic hydrocephalus was similar in both treatment groups ( p = 0.4 ) . Shunt-dependent hydrocephalus occurred in 14 % of surgical cases and 19 % of endovascular cases . This difference did not reach statistical significance ( p = 0.53 ) . Logistic regression models controlling for patient age , WFNS grade , Fisher grade , and acute hydrocephalus in patients with good clinical grade and better Fisher grade revealed no significant difference in the rate of shunt-dependent hydrocephalus in both therapy groups ( odds ratio [ OR ] 0.8 , 95 % confidence interval [ CI ] 0.2 - 2.65 ) . Results of similar models indicated that among patients with intraventricular hemorrhage ( IVH ) , surgical clip application carried a lower risk of shunt-dependent hydrocephalus ( OR 0.32 , 95 % CI 0.14 - 0.75 ) compared with that for endovascular embolization . CONCLUSIONS Shunt-dependent hydrocephalus was comparable in the two treatment groups , even in patients with better clinical and radiological grade s on admission . Only patients in the endovascular therapy group who had experienced IVH showed a higher likelihood of shunt-dependent hydrocephalus |
11,296 | 24,846,217 | These findings typically have not been reflected in experimental research , due possibly to the low doses administered relative to typical self-reported ' real-life ' intake .
AmED consumers generally report more hazardous alcohol consumption patterns and greater engagement in risk-taking behaviour than alcohol consumers .
While most studies had equivocal findings , two studies showed lower odds of risk-taking behaviour for AmED relative to alcohol drinking sessions but limitations with respect to the outcome measures used restrict conclusions with regard to the behavioural outcomes of AmED use .
Mixing alcohol with energy drinks may exert a dual effect , increasing stimulation-based effects and reducing sedation-based outcomes ; the clinical severity and dose threshold has not been established .
At this stage it is unclear whether these changes in the nature of intoxication translate into greater alcohol intake and risk-taking behaviour | AIMS Alcohol mixed with energy drinks ( AmED ) is a relatively new consumption trend generating increasing concern regarding potential adverse effects .
Despite the political and health imperative , there has been no systematic and independent synthesis of the literature to determine whether or not AmED offers additional harms relative to alcohol .
The aim of this study was to review the evidence about whether co-consumption of energy drinks and alcohol , relative to alcohol alone , alters : ( i ) physiological , psychological , cognitive and psychomotor outcomes ; ( ii ) hazardous drinking practice s ; and ( iii ) risk-taking behaviour . | BACKGROUND Previous research on alcohol mixed with energy drinks ( AmED ) suffers from measurement problems . Missing from the research literature are studies that assess caffeine-alcohol co-ingestion in natural drinking environments . METHODS This field study collected data in a U.S. college bar district from 328 r and omly selected patrons . Anonymous data were obtained from face-to-face interviews and self-administered surveys , and from breath tests . RESULTS Cola-caffeinated alcoholic beverage consumers left bars in a more highly intoxicated state than those who consumed alcohol only . There was no significant difference between the intoxication level of the AmED group and the cola-caffeinated alcoholic beverage group . Results from a multivariate regression model indicated that quantity of caffeinated alcoholic beverage consumption had a significant , positive association with bar patron intoxication after adjusting for potential confounders . CONCLUSIONS Findings indicate that caffeine may have a dose-dependent relationship with alcohol intoxication in the bar/nightclub setting . In addition , results revealed that cola-caffeinated alcoholic drinks may pose similar levels of risk to bar patrons as those associated with AmED beverage consumption . Product labeling requirements about alcohol risks may need to be extended not only to energy drinks , but to caffeinated soft drinks as well BACKGROUND There are popular reports on the combined use of alcohol and energy drinks ( such as Red Bull and similar beverages , which contain caffeine , taurine , carbohydrates , etc . ) to reduce the depressant effects of alcohol on central nervous system , but no controlled studies have been performed . The main purpose of this study was to verify the effects of alcohol , and alcohol combined with energy drink , on the performance of volunteers in a maximal effort test ( cycle ergometer ) and also on physiological indicators ( oxygen uptake , ventilatory threshold , respiratory exchange rate , heart rate , and blood pressure ) , biochemical variables ( glucose , lactate , insulin , cortisol , ACTH , dopamine , noradrenaline , and adrenaline ) , and blood alcohol levels . METHODS Fourteen healthy subjects completed a double-blind protocol made up of four sessions : control ( water ) , alcohol ( 1.0 g/kg ) , energy drink ( 3.57 ml/kg Red Bull ) , and alcohol + energy drink , each 1 week apart . The effort test began 60 min after drug or control ingestion , and the dependent variables were measured until 60 min after the test . RESULTS Heart rate at the ventilatory threshold was higher in the alcohol and alcohol + energy drink sessions in comparison with control and energy drink sessions . Although in comparison to the control session , the peak oxygen uptake was 5.0 % smaller after alcohol ingestion , 1.4 % smaller after energy drink , and 2.7 % smaller after the combined ingestion , no significant differences were detected . Lactate levels ( 30 min after drug ingestion , 30 and 60 min after the effort test ) and noradrenaline levels ( 30 min after the effort test ) were higher in the alcohol and alcohol + energy drink sessions compared with the control session . CONCLUSIONS The performance in the maximal effort test observed after alcohol + energy drink ingestion was similar to that observed after alcohol only . No significant differences between alcohol and alcohol + energy drink were detected in the physiological and biochemical parameters analyzed . Our findings suggest that energy drinks , at least in the tested doses , did not improve performance or reduce alterations induced by acute alcohol ingestion BACKGROUND Well-known reports suggest that the use of energy drinks might reduce the intensity of the depressant effects of alcohol . However , there is little scientific evidence to support this hypothesis . OBJECTIVE AND METHODS The present study aim ed at evaluating the effects of the simultaneous ingestion of an alcohol ( vodka(37.5%v/v ) ) and an energy drink ( Red Bull-3.57 mL/kg ) , compared with those presented after the ingestion of an alcohol or an energy drink alone . Twenty-six young healthy volunteers were r and omly assigned to 2 groups that received 0.6 or 1.0 g/kg alcohol , respectively . They all completed 3 experimental sessions in r and om order , 7 days apart : alcohol alone , energy drink alone , or alcohol plus energy drink . We evaluated the volunteers ' breath alcohol concentration , subjective sensations of intoxication , objective effects on their motor coordination , and visual reaction time . RESULTS When compared with the ingestion of alcohol alone , the ingestion of alcohol plus energy drink significantly reduced subjects ' perception of headache , weakness , dry mouth , and impairment of motor coordination . However , the ingestion of the energy drink did not significantly reduce the deficits caused by alcohol on objective motor coordination and visual reaction time . The ingestion of the energy drink did not alter the breath alcohol concentration in either group . CONCLUSIONS Even though the subjective perceptions of some symptoms of alcohol intoxication were less intense after the combined ingestion of the alcohol plus energy drink , these effects were not detected in objective measures of motor coordination and visual reaction time , as well as on the breath alcohol concentration OBJECTIVES The consumption of alcohol mixed with energy drinks ( AmED ) is popular on college campuses in the United States . Limited research suggests that energy drink consumption lessens subjective intoxication in persons who also have consumed alcohol . This study examines the relationship between energy drink use , high-risk drinking behavior , and alcohol-related consequences . METHODS In Fall 2006 , a Web-based survey was conducted in a stratified r and om sample of 4,271 college students from 10 universities in North Carolina . RESULTS A total of 697 students ( 24 % of past 30-day drinkers ) reported consuming AmED in the past 30 days . Students who were male , white , intramural athletes , fraternity or sorority members or pledges , and younger were significantly more likely to consume AmED . In multivariable analyses , consumption of AmED was associated with increased heavy episodic drinking ( 6.4 days vs. 3.4 days on average ; p < 0.001 ) and twice as many episodes of weekly drunkenness ( 1.4 days/week vs. 0.73 days/week ; p < 0.001 ) . Students who reported consuming AmED had significantly higher prevalence of alcohol-related consequences , including being taken advantage of sexually , taking advantage of another sexually , riding with an intoxicated driver , being physically hurt or injured , and requiring medical treatment ( p < 0.05 ) . The effect of consuming AmED on driving while intoxicated depended on a student 's reported typical alcohol consumption ( interaction p = 0.027 ) . CONCLUSIONS Almost one-quarter of college student current drinkers reported mixing alcohol with energy drinks . These students are at increased risk for alcohol-related consequences , even after adjusting for the amount of alcohol consumed . Further research is necessary to underst and this association and to develop targeted interventions to reduce risk AIM To assess event-level associations between energy drink consumption , alcohol intoxication , and intention to drive a motor vehicle in patrons exiting bars at night . METHOD Alcohol field study . Data collected in a U.S. college bar district from 802 r and omly selected and self-selected patrons . Anonymous interview and survey data were obtained as well as breath alcohol concentration ( BrAC ) readings . RESULTS Results from logistic regression models revealed that patrons who had consumed alcohol mixed with energy drinks were at a 3-fold increased risk of leaving a bar highly intoxicated ( BrAC > or = 0.08g/210L ) , as well as a 4-fold increased risk of intending to drive upon leaving the bar district , compared to other drinking patrons who did not consume alcoholic beverages mixed with energy drinks . DISCUSSION These event-level associations provide additional evidence that energy drink consumption by young adults at bars is a marker for elevated involvement in nighttime risk-taking behavior . Further field research is needed to develop sound regulatory policy on alcohol/energy drink sales practice s of on-premise establishments 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 There has been a dramatic rise in the consumption of alcohol mixed with energy drinks ( AmED ) in young people . AmED have been implicated in risky drinking practice s and greater accidents and injuries have been associated with their consumption . Despite the increased popularity of these beverages ( e.g. , Red Bull and vodka ) , there is little laboratory research examining how the effects of AmED differ from alcohol alone . This experiment was design ed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone . METHODS Participants ( n=56 ) attended 1 session where they were r and omly assigned to receive one of 4 doses ( 0.65 g/kg alcohol , 3.57 ml/kg energy drink , AmED , or a placebo beverage ) . Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration . Subjective ratings of stimulation , sedation , impairment , and level of intoxication were recorded . RESULTS Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control , as evidence d by increased inhibitory failures and increased response times compared to baseline performance . Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation , but not response inhibition . For subjective effects , alcohol increased ratings of stimulation , feeling the drink , liking the drink , impairment , and level of intoxication , and alcohol decreased the rating of ability to drive . Coadministration of the energy drink with alcohol increased self-reported stimulation , but result ed in similar ratings of the other subjective effects as when alcohol was administered alone . CONCLUSIONS An energy drink appears to alter some of the objective and subjective impairing effects of alcohol , but not others . Thus , AmED may contribute to a high-risk scenario for the drinker . The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone OBJECTIVE Studies have shown that expectations of alcohol-induced impairment can produce adaptive responses to alcohol that reduce the degree of behavioral impairment displayed . The present study tested psychomotor performance following combined caffeine and alcohol administration in 42 social drinkers ( 23 men ) . Subjects were led to expect either that caffeine would antagonize alcohol-induced impairment or that it would have no effect . The study tested the hypothesis that drinkers who expected an antagonist effect of caffeine would display greater alcohol impairment than those who expected no antagonist effect . METHOD Groups practice d a pursuit rotor task and received a moderate dose of alcohol ( 0.65 g/kg ) combined with either 4.0 mg/kg caffeine or placebo caffeine . Some groups were led to expect that caffeine would counteract the impairing effect of alcohol and others were led to expect no counteracting effect . Psychomotor performance was then tested over a 3-hour period . RESULTS In accord with the hypothesis , groups led to expect counteracting effects of caffeine displayed greater impairment than those led to expect no counteraction . Caffeine had no significant antagonist effect on alcohol impairment . CONCLUSIONS The findings suggest that compensation for alcohol impairment occurs when drinkers hold clear expectations that the drug will disrupt performance . When no such clear expectation exists , no compensatory response occurs and the impairing effects of alcohol are observed The consumption of alcohol mixed with energy drinks ( AmED ) has become a popular and controversial practice among young people . Increased rates of impaired driving and injuries have been associated with AmED consumption . The purpose of this study was to examine if the consumption of AmED alters cognitive processing and subjective measures of intoxication compared with the consumption of alcohol alone . Eighteen participants ( nine men and nine women ) attended four test sessions where they received one of four doses in r and om order ( 0.65 g/kg alcohol , 3.57 ml/kg energy drink , AmED , or a placebo beverage ) . Performance on a psychological refractory period ( PRP ) task was used to measure dual-task information processing and performance on the Purdue pegboard task was used to measure simple and complex motor coordination following dose administration . In addition , various subjective measures of stimulation , sedation , impairment , and level of intoxication were recorded . The results indicated that alcohol slowed dual-task information processing and impaired simple and complex motor coordination . The coadministration of the energy drink with alcohol did not alter the alcohol-induced impairment on these objective measures . For subjective effects , alcohol increased various ratings indicative of feelings of intoxication . More importantly , coadministration of the energy drink with alcohol reduced perceptions of mental fatigue and enhanced feelings of stimulation compared to alcohol alone . In conclusion , AmED may contribute to a high-risk scenario for a drinker . The mix of behavioral impairment with reduced fatigue and enhanced stimulation may lead AmED consumers to erroneously perceive themselves as better able to function than is actually the case Summary . The effects of Red Bull Energy Drink , which includes taurine , glucuronolactone , and caffeine amongst the ingredients , were examined over 3 studies in a total of 36 volunteers . Assessment s included psychomotor performance ( reaction time , concentration , memory ) , subjective alertness and physical endurance . When compared with control drinks , Red Bull Energy Drink significantly ( P < 0.05 ) improved aerobic endurance ( maintaining 65–75 % max . heart rate ) and anaerobic performance ( maintaining max . speed ) on cycle ergometers . Significant improvements in mental performance included choice reaction time , concentration ( number cancellation ) and memory ( immediate recall ) , which reflected increased subjective alertness . These consistent and wide ranging improvements in performance are interpreted as reflecting the effects of the combination of ingredients BACKGROUND There has been a dramatic rise in the consumption of alcohol mixed with energy drinks ( AmEDs ) in social drinkers . It has been suggested that AmED beverages might lead individuals to drink greater quantities of alcohol . This experiment was design ed to investigate whether the consumption of AmEDs would alter alcohol priming ( i.e. , increasing ratings of wanting another drink ) compared with alcohol alone . METHODS Participants ( n = 80 ) of equal gender attended 1 session where they were r and omly assigned to receive 1 of 4 doses ( 0.91 ml/kg vodka , 1.82 ml/kg energy drink , 0.91 ml/kg vodka mixed with 1.82 ml/kg energy drink [ AmED ] , or a placebo beverage ) . Alcohol-induced priming of the motivation to drink was assessed by self-reported ratings on the Desire for Drug question naire . RESULTS The priming dose of alcohol increased the subjective ratings of " desire " for more alcohol , consistent with previous research that small doses of alcohol can increase the motivation to drink . Furthermore , higher desire ratings over time were observed with AmEDs compared with alcohol alone . Finally , ratings of liking the drink were similar for the alcohol and AmED conditions . CONCLUSIONS An energy drink may elicit increased alcohol priming . This study provides laboratory evidence that AmED beverages may lead to greater motivation to drink versus the same amount of alcohol consumed alone BACKGROUND Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose-based mixers has a marked effect on the rate of gastric emptying , result ing in elevated blood alcohol concentrations . Studies conducted in natural drinking setting s , such as bars , have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication . To our knowledge , research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine , that is , diet cola . Therefore , we assessed the event-specific association between diet cola consumption and alcohol intoxication in bar patrons . We sought to determine whether putative increases in blood alcohol , produced by accelerated gastric emptying following diet cola consumption , as identified in the laboratory , also appear in a natural setting associated with impaired driving . METHODS We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 r and omly selected bar patrons in 2008 and 2010 . Data sets were merged and recoded to distinguish between energy drink , regular cola , diet cola , and noncaffeinated alcohol mixers . RESULTS Caffeinated alcohol mixers were consumed by 33.9 % of the patrons . Cola-caffeinated mixed drinks were much more popular than those mixed with energy drinks . A large majority of regular cola-caffeinated mixed drink consumers were men ( 75 % ) , whereas diet cola-caffeinated mixed drink consumers were more likely to be women ( 57 % ) . After adjusting for the number of drinks consumed and other potential confounders , number of diet cola mixed drinks had a significant association with patron intoxication ( β = 0.233 , p < 0.0001 ) . Number of drinks mixed with regular ( sucrose-sweetened ) cola and energy drinks did not have significant associations with intoxication ( p > 0.05 ) . CONCLUSIONS Caffeine 's effect on intoxication may be most pronounced when mixers are artificially sweetened , that is , lack sucrose which slows the rate of gastric emptying of alcohol . Risks associated with on-premise drinking may be reduced by greater attention given to types of mixers , particularly diet colas |
11,297 | 32,122,305 | With succinylcholine regimens ≤0.5 mg kg− 1 , excellent intubating conditions are less likely and apnoea times are shorter , compared with 1 mg kg− 1 .
With 0.3 and 0.4 mg kg− 1 , unacceptable intubating conditions are more common .
Succinylcholine 1.5 mg kg− 1 does not produce more often excellent conditions compared with 1 mg kg− 1 , while 2.0 mg kg− 1 does , but the data base with these regimens is weak and apnoea times remain unknown . | The evidence base for the widely accepted st and ard regimen of succinylcholine for rapid sequence induction ( 1.0 mg kg− 1 ) remains unclear . | STUDY OBJECTIVE To determine the dose of succinylcholine during inhalation induction of a patient . DESIGN ED Prospect i ve , double-blind , r and omized study . SETTING Operating room of a university hospital . PATIENTS 180 adult , ASA physical status 1 and 2 patients with a suspected difficult airway , who were scheduled for surgery . INTERVENTIONS Nonpremedicated patients were anesthetized with inhalation of 8 % sevoflurane , followed by succinylcholine . Group 1 received intravenous ( IV ) succinylcholine 0.3 mg/kg , Group 2 had IV succinylcholine 0.6 mg/kg , and Group 3 was given IV succinylcholine 1.0 mg/kg . Direct laryngoscopy and tracheal intubation were performed after onset of succinylcholine . MEASUREMENTS Intubation conditions were scored as excellent , good , or poor . The recovery time of spontaneous respiration , end-tidal carbon dioxide partial pressure ( PETCO2 ) , and pulse oxygen saturation ( SpO2 ) were recorded . MAIN RESULTS Acceptable conditions ( excellent and good ) for intubation were rated in 80 % of Group 1 patients ( 0.3 mg/kg succhinylcholine ) , 91.7 % of Group 2 patients ( 0.6 mg/kg ) , and 93.3 % of Group 3 patients ( 1.0 mg/kg ) , respectively . Intubation scores were similar in Groups 2 and 3 , and were significantly higher than in Group 1 patients ( 0.3 mg ; P < 0.01 ) . Time to recovery of spontaneous respiration in Group 3 was significantly prolonged compared with Groups 1 and 2 ( 238 ± 59 sec vs 132 ± 43 sec , P < 0.001 ; 238 ± 59 sec vs 151 ± 47 sec , P < 0.001 , respectively ) . SpO2 in Group 3 did not differ significantly from Group 1 and 2 values . However , PETCO2 in Group 3 was significantly higher than in Groups 1 or 2 . CONCLUSIONS Succinylcholine at a dose of 0.6 mg/kg IV provided intubation conditions similar to succinylcholine at 1.0 mg/kg IV , and recovery of spontaneous respiration following a 0.6 mg/kg dose of succinylcholine was significantly shorter We have studied the effectiveness and sequelae of low-dose suxamethonium in 60 day-case oral surgery patients requiring nasal intubation . Anaesthesia was induced with propofol and alfentanil ; 60 patients were allocated r and omly to three groups of 20 patients and received no suxamethonium , suxamethonium 0.25 mg kg-1 or 0.5 mg kg-1 . All patients received i.v . fentanyl and diclofenac 100 mg rectally for analgesia . Good intubating conditions were produced in all 20 patients receiving suxamethonium 0.25 mg kg-1 , in 19 patients receiving suxamethonium 0.5 mg kg-1 and in 11 patients not receiving a neuromuscular blocker . The incidence of postoperative myalgia after suxamethonium 0.25 mg kg-1 ( 20 % ) did not differ significantly from the incidence after propofol and alfentanil alone ( 28 % ) Succinylcholine 1.0 mg/kg usually produces excellent tracheal intubation conditions in 60 s. Recovery of respiratory muscle function after this dose , however , is not fast enough to forestall oxyhemoglobin desaturation when ventilation can not be assisted . In this study , we investigated whether smaller doses of succinylcholine can produce satisfactory intubation conditions fast enough to allow rapid sequence induction with a shorter recovery time . Anesthesia was induced with fentanyl/propofol and maintained by propofol infusion and N2O in O2 . After the induction , 115 patients were r and omly allocated to five groups according to the dose of succinylcholine ( 0.3 mg/kg , 0.4 mg/kg , 0.5 mg/kg , 0.6 mg/kg , or 1.0 mg/kg ) . Evoked adductor pollicis responses to continuous 1-Hz supramaximal ulnar nerve stimulation were recorded using acceleromyography . Tracheal intubation conditions were grade d 60 s after succinylcholine administration . Onset time , maximal twitch depression , time to initial twitch detection after paralysis , and to 10 % , 25 % , 50 % , and 90 % twitch height recovery were recorded . Time to initial diaphragmatic movement as well as time to resumption of regular spontaneous respiratory movements were calculated . Onset times ranged between 82 s and 52 s , decreasing with increasing doses of succinylcholine but not differing between 0.6 and 1 mg/kg . Maximum twitch depression was similar after 0.5 , 0.6 , and 1 mg/kg ( 98.2%–100 % ) . Recoveries of twitch height and apnea time were dose-dependent . Intubation conditions were often unacceptable after 0.3- and 0.4-mg/kg doses . Acceptable intubation conditions were achieved in all patients receiving a 0.5 , 0.6 , and 1 mg/kg dose of succinylcholine . Intubation conditions in patients receiving 0.6 and 1 mg/kg were identical , whereas times to T1 = 50 % and 90 % and time to regular spontaneous reservoir bag movements were significantly shorter in the 0.6-mg/kg dose group ( 5.78 , 7.25 , and 4.0 min , respectively ) versus patients receiving 1 mg/kg ( 8.55 , 10.54 , and 6.16 min , respectively ) . The use of 0.5 to 0.6 mg/kg of succinylcholine can produce acceptable intubation conditions 60 s after administration . The conditions achieved after 0.6 mg/kg are similar to those after 1.0 mg/kg . These smaller doses are associated with faster twitch recovery and shorter apnea time Background : The aim of this prospect i ve , r and omized , double-blind study was to compare tracheal intubating conditions and the duration of apnoea following administration of 0.4 , 0.6 and 1.0 mg/kg of succinylcholine during simulated rapid sequence induction of anaesthesia . Methods : Anaesthesia was induced with fentanyl 2 μg/kg and propofol 2 mg/kg followed by application of cricoid pressure . Patients were r and omly allocated to three groups according to the dose of succinylcholine administered ( 0.4 , 0.6 or 1.0 mg/kg ) . Intubating conditions were assessed at 60 s after succinylcholine administration . Time to first diaphragmatic contraction ( apnoea time ) and time to resumption of regular spontaneous breathing were noted . Results : Excellent intubating conditions were obtained in 52.4 % , 95.7 % and 100 % of the patients after 0.4 , 0.6 and 1.0 mg/kg succinylcholine , respectively ; P<0.001 . Acceptable intubating conditions ( excellent and good grade combined ) were obtained in 66.7 % , 100 % and 100 % of the patients after 0.4 , 0.6 and 1.0 mg/ kg succinylcholine , respectively ; P<0.001 . Apnoea time and resumption of regular spontaneous breathing were dose-dependent . Apnoea time was 3.8±1.1 min , 4.3±0.9 min and 8.2±3.4 min in groups 0.4 , 0.6 and 1.0 mg/kg , respectively ; P<0.001 . Time to regular spontaneous breathing was 5.3±1.2 min , 5.5±1.1 min and 8.9±3.5 min in groups 0.4 , 0.6 and 1.0 mg/kg , respectively ; P<0.001 . Conclusion : A dose of 0.6 mg/kg succinylcholine can be used for rapid sequence induction of anaesthesia as it provides acceptable intubating conditions with a shorter apnoea time compared with a dose of 1 mg/kg Background The usually cited “ intubation dose ” of succinylcholine is 1.0 mg/kg . In the majority of patients , this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted . This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine . Methods During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization , neuromuscular function was recorded with an acceleromyographic monitor . Supramaximal stimuli were delivered at 0.10 Hz . Patients received 0.40 , 0.60 , or 1.0 mg/kg succinylcholine , and twitch height was monitored for at least 20 min thereafter . Results The onset times to maximal effect were 105 ± 23 s , 81 ± 19 s , and 71 ± 22 s , respectively . The lowest dose ( 0.40 mg/kg ) did not reliably produce 100 % twitch depression . The times to 90 % twitch recovery at the adductor pollicis in the three groups were 6.6 ± 1.5 min , 7.6 ± 1.6 min , and 9.3 ± 1.2 min , respectively . Conclusions Reducing the dose of succinylcholine from 1.0 mg/kg to 0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than 90 s. The authors believe that even this modest decrease in the duration of drug-induced paralysis is often worth pursuing Background The authors reappraised the conventional wisdom that the intubating dose of succinylcholine must be 1.0 mg/kg and attempted to define the lower range of succinylcholine doses that provide acceptable intubation conditions in 95 % of patients within 60 s. Methods This prospect i ve , r and omized , double-blind study involved 200 patients . Anesthesia was induced with 2 & mgr;g/kg fentanyl and 2 mg/kg propofol . After loss of consciousness , patients were r and omly allocated to receive 0.3 , 0.5 , or 1.0 mg/kg succinylcholine or saline ( control group ) . Tracheal intubation was performed 60 s later . A blinded investigator performed all laryngoscopies and also grade d intubating conditions . Results Intubating conditions were acceptable ( excellent plus good grade combined ) in 30 % , 92 % , 94 % , and 98 % of patients after 0.0 , 0.3 , 0.5 , and 1.0 mg/kg succinylcholine , respectively . The incidence of acceptable intubating conditions was significantly greater ( P < 0.05 ) in patients receiving succinylcholine compared with those in the control group but was not different among the different succinylcholine dose groups . The calculated doses of succinylcholine ( and their 95 % confidence intervals ) that were required to achieve acceptable intubating conditions in 90 % and 95 % of patients at 60 s were 0.24 ( 0.19–0.31 ) mg/kg and 0.56 ( 0.43–0.73 ) mg/kg , respectively . Conclusions The use of 1.0 mg/kg of succinylcholine may be excessive if the goal is to achieve acceptable intubating conditions within 60 s. Comparable intubating conditions were achieved after 0.3 , 0.5 , or 1.0 mg/kg succinylcholine . In a rapid-sequence induction , 95 % of patients with normal airway anatomy anesthetized with 2 & mgr;g/kg fentanyl and 2 mg/kg propofol should have acceptable intubating conditions at 60 s after 0.56 mg/kg succinylcholine . Reducing the dose of succinylcholine should allow a more rapid return of spontaneous respiration and airway reflexes In this prospect i ve , r and omized , double-blind , placebo-controlled study , we attempted to define the dose of succinylcholine that provides excellent intubation conditions in patients within 60 s during simulated rapid-sequence induction of anesthesia . Anesthesia was induced in 180 patients with 2 & mgr;g/kg fentanyl and 2 mg/kg propofol . After loss of consciousness , patients were r and omly allocated to receive 0.3 , 0.5 , 1.0 , 1.5 , or 2.0 mg/kg succinylcholine or saline solution ( control group ) . Tracheal intubation was performed 60 s later . A blinded investigator performed all laryngoscopies and grade d intubating conditions . Intubating conditions were excellent in 0.0 % , 43.3 % , 60.0 % , 63.3 % , 80.0 % , and 86.7 % of patients after 0.0 , 0.3 , 0.5 , 1.0 , 1.5 , and 2.0 mg/kg succinylcholine , respectively . The incidence of excellent intubating conditions was significantly more frequent ( P < 0.001 ) in patients receiving succinylcholine than in the controls and in patients who received 2.0 mg/kg succinylcholine ( P < 0.05 ) than in those who received 0.3 mg/kg succinylcholine . The calculated doses of succinylcholine ( and their 95 % confidence intervals ) that are required to achieve excellent intubating conditions in 50 % and 80 % of patients at 60 s are 0.39 ( 0.29–0.51 ) mg/kg and 1.6 ( 1.2–2.0 ) mg/kg , respectively . It appears that there are no advantages to using doses of succinylcholine larger than 1.5 mg/kg The appropriate dose of succinylcholine ( SCH ) in morbidly obese patients is unknown . We studied 45 morbidly obese ( body mass index > 40 kg/m2 ) adults scheduled for gastric bypass surgery . The response to ulnar nerve stimulation of the adductor pollicis muscle at the wrist was recorded using the TOF-Watch SX ® acceleromyograph . In a r and omized double-blind fashion , patients were assigned to one of three study groups . In Group I , patients received SCH 1 mg/kg ideal body weight , in Group II 1 mg/kg lean body weight , and in Group III 1 mg/kg total body weight . After SCH administration , endotracheal intubating conditions were scored . The recovery from neuromuscular block was recorded for 20 min . There was no difference in the onset time of maximum neuromuscular blockade among groups , but maximum block was significantly less in Group I. The recovery intervals were significantly shorter in Groups I and II . In one third of the patients in Group I , intubating conditions were rated poor , whereas no patient in Group III had poor intubating conditions . Our study demonstrates that for complete neuromuscular paralysis and predictable laryngoscopy conditions , SCH 1 mg/kg total body weight is recommended In a double‐blind study , 67 young adult patients undergoing anaesthesia for dental extraction s were allocated at r and om to receive either 0.5 mg/kg or 1.5 mg/kg suxamethonium . A greater increase in arterial pressure was seen following induction in the 1.5 mg/kg group , although overall intubating conditions were similar in the two groups . Suxamethonium‐associated muscle pains were significantly more common in the group which received the larger dose ( p>0.05 ) BACKGROUND This study was conducted to compare outcomes of different doses of succinylcholine , in terms of intubation condition , onset of action , duration of action and abdominal fasciculation . METHODS Thus , r and omized control trial was conducted in the department of anaesthesia and ICU , Nishter Hospital Multan from April 2016 to November 2016 . A total number of 60 patients with ASA status I and II were enrolled . All patients were divided into three groups by lottery method . Data was entered and analysed by computer software SPSS version 23.2 . Descriptive variables like age and onset of action were presented as mean and SD and continues statistics like gender , abdominal fasciculation and incubation condition were presented as frequency and percentages . Chi square test and one-way ANOVA was applied to see effect modification and significance of results . The p-value 0.05 was considered as significant . RESULTS A Total number of 60 patients included in this study and all were female . The mean age of the patients was 28.15±4.5 years . The main outcome variables of this study were the fasciculation , satisfactory intubation , onset time ( seconds ) and duration of action ( in minutes ) . In group ( A ) 1 mg , abdominal fasciculation was found 80 % , 85 % and 75 % in group A , B , C respectively . It was also observed that satisfactory intubation was found 90 % , 80 % and 30 % in three groups respectively . The mean onset time was 50.95±4.6 , 70.7±5.66 and 94.15±8.73 seconds in three groups respectively . Similarly , the mean duration of action was 16.1±3.76 , 13.55±3.01 and 8±2.05 minutes respectively . CONCLUSIONS Results of our clinical trial suggest that succinylcholine in low doses shorter duration of action and low rate of abdominal fasciculation which is desirable for rapid induction but onset of action is prolonged and intubation conditions were not satisfactory predominantly . So , we concluded that low doses of succnylcholine are not so much beneficial that I can replace full doses of succinylcholine when used for rapid induction and intubation |
11,298 | 24,902,842 | Conclusions This systematic review reveals a lack of underst and ing of PCC within dentistry , and in particular general dental practice .
There is currently a poor evidence base to support the use of the current patient reported outcome measures as indicators of patient-centredness . | Background Delivering improvements in quality is a key objective within most healthcare systems , and a view which has been widely embraced within the NHS in the United Kingdom .
Within the NHS , quality is evaluated across three key dimensions : clinical effectiveness , safety and patient experience , with the latter modelled on the Picker Principles of Patient-Centred Care ( PCC ) .
Quality improvement is an important feature of the current dental contract reforms in Engl and , with “ patient experience ” likely to have a central role in the evaluation of quality .
An underst and ing and appreciation of the evidence underpinning PCC within dentistry is highly relevant if we are to use this as a measure of quality in general dental practice . | A survey was carried out asking patients to evaluate the criteria of good dental practice proposed by patients and dentists . A total of 344 patients from 4 different general dental practice s in South East Engl and evaluated 16 criteria of good dental practice . Eight criteria were generated by 30 general dental practitioners and the other eight by 30 patients . Question naires containing the 8 pairs of criteria r and omly assigned by a computer were drawn up , with each pair containing one patient and one general dental practitioner criterion . Patients were asked to indicate their preference . The number of times each criterion was preferred was scored and ranked . The three highest ranked criteria were explanation of procedures , sterilisation/hygiene and dentist 's skills ( all criteria proposed from patients ) , whilst the three lowest ranked criteria were up-to- date equipment , pleasant decor and surroundings and good practice image ( all criteria proposed from dentists ) . Overall the criteria proposed by patients as a group scored significantly more highly than those proposed by dentists as a group . There was variation in rankings relating to the sex , age , pattern of attendance and social class of the respondents Background Precisely defining the different applications of patient-reported outcome measures ( PROs ) in clinical practice can be difficult . This is because the intervention is complex and varies amongst different studies in terms of the type of PRO used , how the PRO is fed back , and to whom it is fed back . Methods A theory-driven approach is used to describe six different applications of PROs in clinical practice . The evidence for the impact of these applications on the process and outcomes of care are summarised . Possible explanations for the limited impact of PROs on patient management are then discussed and directions for future research are highlighted . Results The applications of PROs in clinical practice include screening tools , monitoring tools , as a method of promoting patient-centred care , as a decision aid , as a method of facilitating communication amongst multidisciplinary teams ( MDTs ) , and as a means of monitoring the quality of patient care . Evidence from r and omised controlled trials suggests that the use of PROs in clinical practice is valuable in improving the discussion and detection of HRQoL problems but has less of an impact on how clinicians manage patient problems or on subsequent patient outcomes . Many of the reasons for this may lie in the ways in which PROs fit ( or do not fit ) into the routine ways in which patients and clinicians communicate with each other , how clinicians make decisions , and how healthcare as a whole is organised . Conclusions Future research needs to identify ways in with PROs can be better incorporated into the routine care of patients by combining qualitative and quantitative methods and adopting appropriate trial design BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals OBJECTIVE This paper defines an interactional analysis instrument to characterize patient-centered care and identify associated variables . METHODS In this study , 509 new adult patients were r and omized to care by family physicians and general internists . An adaption of the Davis Observation Code was used to measure a patient-centered practice style . The main outcome measures were visit-specific satisfaction and healthcare re source utilization . RESULTS In initial primary care visits , patient-centered practice style was positively associated with higher patient self-reported physical health status ( p=0.0328 ) , higher educational level ( p=0.0050 ) , and non-smoking status ( p=0.0108 ) ; it was also observed more often in the interactions of family physicians compared to internists ( p=0.0003 ) . Controlling for patient sociodemographic variables , self-reported health status , pain , health risk behaviors ( obesity , alcohol abuse , and smoking ) , and clinic assignment , patient satisfaction was not related to the provision of patient-centered care . Moreover , a higher average amount of patient-centered care recorded in visits throughout the one-year study period was significantly related to lower annual medical charges ( p=0.0003 ) . CONCLUSIONS Patient-centered care was observed more often with family physician caring for healthier , more educated patients , and was associated with lower charges . PRACTICE IMPLICATION S Reduced annual medical care charges are an important outcome of patient-centered medical visits Purpose : This article uses an interactional analysis instrument to characterize patient-centered care in the primary care setting and to examine its relationship with health care utilization . Methods : Five hundred nine new adult patients were r and omized to care by family physicians and general internists . An adaption of the Davis Observation Code was used to measure a patient-centered practice style . The main outcome measures were their use of medical services and related charges monitored over 1 year . Results : Controlling for patient sex , age , education , income , self-reported health status , and health risk behaviors ( obesity , alcohol abuse , and smoking ) , a higher average amount of patient-centered care recorded in visits throughout the 1-year study period was related to a significantly decreased annual number of visits for specialty care ( P = .0209 ) , less frequent hospitalizations ( P = .0033 ) , and fewer laboratory and diagnostic tests ( P = .0027 ) . Total medical charges for the 1-year study were also significantly reduced ( P = .0002 ) , as were charges for specialty care clinic visits ( P = .0005 ) , for all patients who had a greater average amount of patient-centered visits during that same time period . For female patients , the regression equation predicted 15.47 % of the variation in total annual medical charges compared with male patients , for whom 31.18 % of the variation was explained by the average percent of patient-centered care , controlling for sociodemographic variables , health status , and health risk behaviors . Conclusions : Patient-centered care was associated with decreased utilization of health care services and lower total annual charges . Reduced annual medical care charges may be an important outcome of medical visits that are patient-centered |
11,299 | 29,389,735 | Mitochondrial function and dysfunction also contribute to systemic physiological regulation through the release of mitokines and other metabolites .
At the cellular level , mitochondrial signaling influences gene expression and epigenetic modifications , and modulates the rate of cellular aging .
Conclusions This evidence suggests that mitochondrial allostatic load represents a potential subcellular mechanism for transducing psychosocial experiences and the result ing emotional responses — both adverse and positive — into clinical ly meaningful biological and physiological changes . | Background The integration of biological , psychological , and social factors in medicine has benefited from increasingly precise stress response biomarkers .
Mitochondria , a subcellular organelle with its own genome , produce the energy required for life and generate signals that enable stress adaptation .
An emerging concept proposes that mitochondria sense , integrate , and transduce psychosocial and behavioral factors into cellular and molecular modifications .
Mitochondrial signaling might in turn contribute to the biological embedding of psychological states .
Results Chronically , psychological stress induces metabolic and neuroendocrine mediators that cause structural and functional recalibrations of mitochondria , which constitutes mitochondrial allostatic load .
Clinical ly , primary mitochondrial defects affect the brain , the endocrine system , and the immune systems that play a role in psychosomatic processes , suggesting a shared underlying mechanistic basis . | In this paper , Choi and colleagues analyzed levels of mitochondrial DNA in two prospect i ve observational cohort studies and found that increased mtDNA levels are associated with ICU mortality , and improve risk prediction in medical ICU patients . The data suggests that mtDNA could serve as a viable plasma biomarker in MICU patients We propose a model wherein chronic stress results in glucocorticoid receptor resistance ( GCR ) that , in turn , results in failure to down-regulate inflammatory response . Here we test the model in two viral-challenge studies . In study 1 , we assessed stressful life events , GCR , and control variables including baseline antibody to the challenge virus , age , body mass index ( BMI ) , season , race , sex , education , and virus type in 276 healthy adult volunteers . The volunteers were subsequently quarantined , exposed to one of two rhinoviruses , and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold . In study 2 , we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local ( in nasal secretions ) proinflammatory cytokines ( IL-1β , TNF-α , and IL-6 ) . Study 1 : After covarying the control variables , those with recent exposure to a long-term threatening stressful experience demonstrated GCR ; and those with GCR were at higher risk of subsequently developing a cold . Study 2 : With the same controls used in study 1 , greater GCR predicted the production of more local proinflammatory cytokines among infected subjects . These data provide support for a model suggesting that prolonged stressors result in GCR , which , in turn , interferes with appropriate regulation of inflammation . Because inflammation plays an important role in the onset and progression of a wide range of diseases , this model may have broad implication s for underst and ing the role of stress in health Objective Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses . This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function . Methods A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted . The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria . Results A total of 23 studies met the inclusion criteria . All studies involved male laboratory animals , and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function , particularly within the brain . Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress . In humans , only six observational studies were available , none with experimental design s , and most only measured biological markers that do not directly reflect mitochondrial function , such as mitochondrial DNA copy number . Conclusons Overall , evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology , and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria . Limitations of current animal and human studies are discussed . Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load . Prospect i ve studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors , emotional states , the result ing neuroendocrine and immune processes , and mitochondrial energetics relevant to mind-body research in humans Mitochondrial components , including mitochondrial DNA ( mtDNA ) , when released extracellularly , can act as " damage-associated molecular pattern " ( DAMP ) agents and cause inflammation . As many elderly people are characterized by a low- grade , chronic inflammatory status defined " inflamm-aging , " we evaluated if circulating mtDNA can contribute to this phenomenon . Eight hundred and thirty-one Caucasian subjects were enrolled in the study , including 429 siblings aged 90 - 104 ( 90 + siblings ) . mtDNA plasma levels increased gradually after the fifth decade of life . In 90 + subjects , mtDNA values of two members of the same sibling relationship were directly correlated , suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA . The subjects with the highest mtDNA plasma levels had the highest amounts of TNF-α , IL-6 , RANTES , and IL-1ra ; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines . In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo result ed in an increased production of TNF-α , suggesting that mtDNA can modulate the production of proinflammatory cytokines . Our findings therefore show that circulating mtDNA increases with age , and can significantly contribute to the maintenance of the low- grade , chronic inflammation observed in elderly people BACKGROUND Decreased hippocampal volume is observed in patients with Cushing 's syndrome and other conditions associated with elevated cortisol levels , stress , or both . Reversibility of hippocampal neuronal atrophy result ing from stress occurs in animals . Our study investigated the potential for reversibility of human hippocampal atrophy . METHODS The study included 22 patients with Cushing 's disease . Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment . RESULTS Following treatment , hippocampal formation volume ( HFV ) increased by up to 10 % . The mean percent change ( 3.2 + /- 2.5 ) was significantly greater ( p < .04 ) than that of the comparison structure , cau date head volume ( 1.5 + /- 3.4 ) . Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol ( r = -.61 , p < .01 ) . This relationship strengthened after adjustments for age , duration of disease , and months elapsed since surgery ( r = -.70 , p < .001 ) . There was no significant correlation between cau date head volume change and magnitude of cortisol decrease . CONCLUSIONS Changes in human HFV associated with sustained hypercortisolemia are reversible , at least in part , once cortisol levels decrease . While many brain regions are likely affected by hypercortisolemia , the human hippocampus exhibits increased sensitivity to cortisol , affecting both volume loss and recovery Objective : To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus ( DM ) compared to age-matched control subjects . Methods : From a r and omized controlled trial ( PROSPER study ) , a study sample of 89 patients with DM and 438 control subjects without DM aged 70–82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years . Changes in brain atrophy , white matter hyperintensities ( WMHs ) , number of infa rct ions , and cognitive function test results were determined in patients with DM and subjects without DM . Linear regression analysis was performed with correction for age , gender , hypertension , pravastatin treatment , educational level , and baseline test results . In patients with DM , baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender . Results : Patients with DM showed increased progression of brain atrophy ( p < 0.01 ) after follow-up compared to control subjects . No difference in progression of WMH volume or infa rct ions was found . Patients with DM showed increased decline in cognitive performance on Stroop Test ( p = 0.04 ) and Picture Learning Test ( p = 0.03 ) . Furthermore , in patients with DM , change in Picture Learning Test was associated with baseline brain atrophy ( p < 0.02 ) . Conclusion : Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM . Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function BACKGROUND Pre clinical studies demonstrate that the neonatal environment can permanently alter an individual 's responses to stress . To demonstrate a similar phenomenon in humans , we prospect ively examined the relationships of maternal stress beginning in infancy and concurrent stress on preschoolers ' hypothalamic-pituitary-adrenal activity and later mental health symptoms . METHODS Salivary cortisol levels were assessed in 282 4.5-year-old children and 154 of their siblings . Maternal reports of stress were obtained when the children were ages 1 , 4 , and 12 months , and again at 4.5 years . Children 's mental health symptoms were assessed in first grade . RESULTS A cross-sectional analysis revealed that preschoolers exposed to high levels of concurrent maternal stress had elevated cortisol levels ; however , a longitudinal analysis revealed that concurrently stressed children with elevated cortisol also had a history of high maternal stress exposure in infancy . Importantly , children exposed only to high levels of concurrent or early stress had cortisol levels that did not significantly differ from those never exposed to stress . Further analysis of the components of stress indicated that maternal depression beginning in infancy was the most potent predictor of children 's cortisol . We also found that preschoolers with high cortisol levels exhibited greater mental health symptoms in first grade . CONCLUSIONS These results link the findings of pre clinical studies to humans by showing that exposure to early maternal stress may sensitize children 's pituitary-adrenal responses to subsequent stress exposure OBJECTIVE — We determined whether reduced insulin sensitivity , mitochondrial dysfunction , and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity . RESEARCH DESIGN AND METHODS — Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young ( 18–30 years old ) and older ( 59–76 years old ) subjects . Expression of proteins involved in fuel metabolism was measured by mass spectrometry . Citrate synthase activity , mitochondrial DNA ( mtDNA ) abundance , and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured . SIRT3 , a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction , was measured by immunoblot . RESULTS — Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects , but no age effect was noted . Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals . Although endurance-trained individuals exhibited higher expression of mitochondrial proteins , mtDNA , and mitochondrial transcription factors , there were persisting effects of age . SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals . CONCLUSIONS — The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging . The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction , although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein . Furthermore , exercise may promote longevity through pathways common to effects of caloric restriction Chronic stress in non-human animals decreases the volume of the hippocampus , a brain region that supports learning and memory and that regulates neuroendocrine activity . In humans with stress-related psychiatric syndromes characterized by impaired learning and memory and dysregulated neuroendocrine activity , surrogate and retrospective indicators of chronic stress are also associated with decreased hippocampal volume . However , it is unknown whether chronic stress is associated with decreased hippocampal volume in those without a clinical syndrome . We tested whether reports of life stress obtained prospect ively over an approximate 20-year period predicted later hippocampal grey matter volume in 48 healthy postmenopausal women . Women completed the Perceived Stress Scale repeatedly from 1985 to 2004 ; in 2005 and 2006 , their hippocampal grey matter volume was quantified by voxel-based morphometry . Higher Perceived Stress Scale scores from 1985 to 2004 - an indicator of more chronic life stress - predicted decreased grey matter volume in the right orbitofrontal cortex and right hippocampus . These relationships persisted after accounting for age , total grey matter volume , time since menopause , use of hormone therapy , sub clinical depressive symptoms , and other potentially confounding behavioral and age-related cerebrovascular risk factors . The relationship between chronic life stress and regional grey matter volume - particularly in the hippocampus and orbitofrontal cortex - appears to span a continuum that extends to otherwise healthy individuals . Consistent with animal and human clinical evidence , we speculate that chronic-stress-related variations in brain morphology are reciprocally and functionally related to adaptive and maladaptive changes in cognition , neuroendocrine activity , and psychiatric vulnerability Abstract The Whitehall Study is a prospect i ve epidemiological study of cardiovascular risk factors in healthy members of the British Civil Service , which has identified psychological distress as a major risk factor for coronary heart disease . The levels of circulating Hsp60 in 860 participants from the Whitehall cohort and 761 individuals diagnosed with diabetes have been measured and related to psychological , biological , and genetic factors . In the Whitehall participants , concentrations of Hsp60 ranged from undetectable to mg/mL levels . Circulating Hsp60 correlated with total and low-density lipoprotein ( LDL ) cholesterol and was positively associated with a flattened slope of cortisol decline over the day . Levels of this stress protein also correlated with measures of psychological stress including psychological distress , job dem and , and low emotional support . Mass spectrometric analysis of circulating immunoreactive Hsp60 reveal that it is predominantly the intact protein with no mitochondrial import peptide , suggesting that this circulating protein emanates from mitochondria . The Hsp60 is stable when added to plasma and the levels in the circulation of individuals are remarkably constant over a 4-year period , suggesting plasma levels are partly genetically controlled . Sequence analysis of the HSP60-HSP10 intergenic promoter region identified a common variant 3175 C > G where the G allele had a frequency of 0.30 and was associated with higher Hsp60 levels in 761 type 2 diabetic patients . The extended range of plasma Hsp60 concentrations in the general population is genuine and is likely to be related to genetic , biological , and psychosocial risk factors for coronary artery disease Healthy men exhibit a differential hypothalamic-pituitary-adrenal axis ( HPA ) response to exercise stress and fall into two groups : high responders ( HR ) and low responders ( LR ) . The present study examined whether HR to physical stress also exhibit higher HPA reactivity to psychological stress than LR . We examined 14 HR and 13 LR classified based on their ACTH responses to high intensity exercise after pretreatment with dexamethasone . Both groups were of similar age , height , weight , and fitness level . Trait anxiety scores on the Spielberger Trait Anxiety Scale were not different . Subjects underwent a psychological stress test consisting of an interview and mental arithmetic . This test raised heart rate , blood pressure , and plasma ACTH and cortisol levels in both HR and LR . HR tended to have higher heart rates and blood pressures in anticipation of the psychological stress test than LR . ACTH responses of HR were higher , although not significantly , throughout the psychological stress test than LR . HR had a significantly ( P < 0.05 ) greater net integrated cortisol response to the psychological stress than LR . This suggests that the adrenal cortexes of the HR are hypertropic and /or hypersensitive to ACTH . We conclude that men who are highly responsive to exercise stress are also highly responsive to psychological stress Studies in persons of European descent have suggested that mitochondrial DNA ( mtDNA ) haplogroups influence antiretroviral therapy ( ART ) toxicity . We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white , ART-naive subjects starting ART . A5152s was a sub study of A5142 , a r and omized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors ( NRTIs ) , or both without NRTIs . Brachial artery flow-mediated dilation ( FMD ) and cardiovascular biomarker assessment s were performed at baseline and at weeks 4 and 24 . Ten haplogroup-defining mtDNA polymorphisms were determined . FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests . Thirty-nine non-Hispanic white participants had DNA and 24-week data . The nonsynonymous m.10398A > G mtDNA polymorphism ( N=8 ) was associated with higher median baseline adiponectin ( 5.0 vs. 4.2 μg/ml ; p=0.003 ) , greater absolute ( -1.9 vs. -0.2 μg/ml ) and relative ( -33 % vs. -3 % ) adiponectin decreases ( p<0.001 for both ) , and lower week 24 brachial artery FMD ( 3.6 % vs. 5.4 % ; p=0.04 ) . Individual mtDNA haplogroups , including haplogroups H ( N=13 ) and U ( N=6 ) , were not associated with adiponectin or FMD changes . In this small pilot study , adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases . These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects . Validation studies in larger population s and in different racial/ethnic groups that include m.10398 G carriers are needed Experimental evidence shows that telomere shortening induces mitochondrial damage but so far studies in humans are scarce . Here , we investigated the association between leukocyte telomere length ( LTL ) and mitochondrial DNA ( mtDNA ) content in elderly and explored possible intermediate mechanisms by determining the gene expression profile of c and i date genes in the telomere-mitochondrial axis of ageing . Among 166 non-smoking elderly , LTL , leukocyte mtDNA content and expression of c and i date genes : sirtuin1 ( SIRT1 ) , tumor protein p53 ( TP53 ) , peroxisome proliferator-activated receptor γ-coactivator1α ( PGC-1α ) , peroxisome proliferator-activated receptor γ-coactivator1β ( PGC-1β ) , nuclear respiratory factor 1 ( NRF1 ) and nuclear factor , erythroid 2 like 2 ( NRF2 ) , using a quantitave real time polymerase chain assay ( qPCR ) . Statistical mediation analysis was used to study intermediate mechanisms of the telomere-mitochondrial axis of ageing . LTL correlated with leukocyte mtDNA content in our studied elderly ( r = 0.23 , p = 0.0047 ) . SIRT1 gene expression correlated positively with LTL ( r = 0.26 , p = 0.0094 ) and leukocyte mtDNA content ( r = 0.43 , p < 0.0001 ) . The other studied c and i date s showed significant correlations in the telomere-mitochondrial interactome but not independent from SIRT1 . SIRT1 gene expression was estimated to mediate 40 % of the positive association between LTL and leukocyte mtDNA content . The key finding of our study was that SIRT1 expression plays a pivotal role in the telomere-mitochondrial interactome We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy ( HA ) in a research clinic population of 130 normal elderly , 72 nondemented patients with very mild memory and cognitive impairments ( MCI ) , 73 mild Alzheimer 's disease ( AD ) patients , and 130 patients with moderate to severe AD . HA was found in 29 % of the normal elderly group and its frequency of occurrence was strongly related to increasing age . For normal elderly 60 - 75 years of age , 15 % had HA : the proportion rose to 48 % in subjects 76 - 90 years of age . Among the three groups of impaired patients , the frequencies of HA ranged from 78 % in the MCI patients to 96 % in the advanced AD group . Unlike the normal elderly group , the percentages were not related to age . In both the normal elderly group and MCI group disproportionately more males than females had HA . After controlling for learning and the effects of generalized brain changes as reflected in ventricular size , only in the normal group was HA associated with reduced delayed verbal recall performance . Follow-up examinations for 15 individuals with baseline HA . 4 who at entry were MCI and 11 probable AD , yielded clinical and neuropathologic diagnoses of AD in all cases . The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments . Further longitudinal and neuropathologic work is required to vali date the relationship between hippocampal formation atrophy and AD |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.